Metal-Catalyzed Reactions in Water (Dixneuf/Metal-Catalyzed Reactions in Water) || Metal-Catalyzed...

47

2Metal-Catalyzed C–H Bond Activation and C–C Bond Formationin WaterBin Li and Pierre H. Dixneuf

2.1Introduction

The catalytic C–H bond functionalization in water is still a challenge and constitutesan excellent contribution to green chemistry, as it focuses on the development ofnew chemical reactivities and reaction conditions providing advantages for chemicalsynthesis [1].

The activation of inert C–H bonds for their direct catalytic formation ofC–C bonds is bringing a revolution in synthetic methodology for the fast pro-duction of highly functionalized molecules including molecular materials. Thecatalytic cross-coupling reactions from C–H bonds will soon replace many clas-sical cross-coupling reactions, involving the previous preparation of one or twoorganometallic derivatives and reaction with (hetero)aryl halides. A variety of metalcatalysts, initially palladium and rhodium derivatives, can now perform efficientlythe regioselective cross-coupling reactions from numerous C–H bonds in organicsolvents [2]. The less expensive metal catalysts, such as ruthenium(0) and es-pecially stable ruthenium(II) catalysts, have been shown to promote the directfunctionalization of sp2C–H bonds under mild conditions [3, 4].

Although the catalytic C–H bond functionalization constitutes a green contri-bution with atom economy to cross-coupling reactions, most of these reactionshave been shown to be successful in organic solvents. A greener step involves itsperformance in water, which is a safe, a low-cost, and an easily available solvent andwhich allows easy workup and product separation. However, innovative C–H bondactivation processes in water need to be discovered before they become generallyapplied.

Already a large number of metal-catalyzed reactions have been successfullyperformed in water [5, 6]. Many C–H bond functionalizations have been shown toinvolve as an initial activation step a C–H bond deprotonation, assisted by a metalcatalyst, such as Pd(II), Ru(II), or Rh(III), and a coordinated basic ligand, such ascarbonate or carboxylate [2, 3d, 4, 7]. This process should not be affected by thepresence of water. Water is an attractive solvent but a poor solvent for most organiccompounds. Owing to the low solubility of C–H bond containing organic molecules

Metal-Catalyzed Reactions in Water, First Edition. Edited by Pierre H. Dixneuf and Victorio Cadierno. 2013 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2013 by Wiley-VCH Verlag GmbH & Co. KGaA.

48 2 Metal-Catalyzed C–H Bond Activation and C–C Bond Formation in Water

in water, without water-soluble functions, most of the C–H bond functionalizationsin water are consistent with ‘‘on-water’’ reactions [8]. Water is also attractive as it, ina few examples, can increase the activity of the catalyst with respect to the organicsolvent.

There are already numerous examples of alkyne spC–H bond catalytic additionto reactive intermediates in water, as it is easy to activate and deprotonate terminalalkyne spC–H bond. Several reviews on that topic have already appeared and shownumerous applications in water [9].

By contrast, only a few examples of the catalytic functionalization of sp2C–H bondin water have been performed [10, 11] in spite of their potential for cross-couplingreactions. Another frequent type of C–H bond functionalization involves thecross-dehydrogenative coupling (CDC) with an sp3C–H bond, usually arising atthe adjacent carbon of a heteroatom [12]. Several examples of this catalytic reactionhave been carried out in water.

The objective of this chapter is to present the developments of metal-catalyzedfunctionalization of C–H bonds in water for the selective formation ofcarbon–carbon bonds until the end of 2011. The catalytic spC–H bond additionsin water have been previously very well developed and presented in reviews by Ligroup [9]. After the rapid presentation of spC–H bond functionalization in water,this chapter summarizes the sp2C–H bond activation leading to catalytic C–Ccross-coupling reactions in water and presents the main examples of C–C bondformation from sp3C–H bonds in water.

2.2Catalytic Formation of C–C Bonds from spC–H Bonds in Water

2.2.1Catalytic Nucleophilic Additions of Alkynes in Water

The catalytic addition of terminal alkynes to electrophiles such as C=O and C=Nbonds of aldehydes, ketones, and imines in water has now been largely developedwith various catalytic systems, especially by Li group [13] (Equation 2.1). It is basedon the in situ formation of alkynyl metal species due to the relative acidity ofterminal alkynes before nucleophilic addition. This general method of synthesisof propargylic derivatives in water has been presented in several reviews [9] andhas even been successfully applied to enantioselective transformations [14]. Thiscatalytic addition of alkynes in water is presented in Chapter 3 of this volume [15].

RNHAr

R1R H

NAr

R1

ROH

R1

O

R1

ArNH2

Catalyst/water Catalyst/water

(2.1)

2.2 Catalytic Formation of C–C Bonds from spC–H Bonds in Water 49

2.2.2Addition of Terminal Alkynes to C≡C Bonds in Water

The catalytic dimerization of terminal alkynes into Z-enynes has been performedin water using a ruthenium catalyst RuH(CH3CN)[N(CH2CH2PPh2)3]OTF (Ru(II)Cat.) (Equation 2.2) [16]. The reaction was successfully applied to both aryl and alkylacetylenes, and although it corresponds to the formal insertion of an alkyne intothe other spC–H bond, it was shown to take place via the formation of a vinylidenemoiety Ru=C=CHR inserting into the (alkynyl)C-Ru bond.

R HRu(II) Cat

H2O/100 °C

R

H H

R

2 (2.2)

Recently, the selective formation of E-enynes from terminal alkynes was achievedat room temperature in a AcOH/H2O medium, using a simple ruthenium(II)catalyst [RuCl2(C6Me6)]2 (Equation 2.3) [17]. The in situ formed Ru(OAc)(X)(arene)complex (X=Cl, OAc) favors the formation of alkynyl–ruthenium bond via ac-etate promoted C–H bond deprotonation, followed by insertion of the vinylideneintermediate.

Ar H[RuCl2(C6Me6)]2

AcOH:H2O (1 : 1), rt

Ar

Ar

2

(2.3)

The addition of a terminal alkyne to a disubstituted electron-deficient alkynewas achieved by Li [18], using a Cu(I)/Pd(II) catalytic system operating in wa-ter (Equation 2.4). This reaction is consistent with a conjugate addition of thealkynyl-copper intermediate and takes place without alkyne homocoupling.

H + CO2Me

CuBr (5 mol%)PdCl2(PPh3)2 (2.5 mol%)

H2O, 60 °C CO2Me(2.4)

2.2.3The Sonogashira-Type Reactions in Water

The Sonogashira reaction is the C–C cross-coupling reaction of terminal alkynewith (hetero)aryl bromides or chlorides, and it is usually promoted by both Pd(0)and Cu(I) catalysts. Several examples of this catalytic reaction have now beenperformed in water and are presented in this chapter. Further developments of theSonogashira reaction in water can be found in the previous chapter [19].

It was shown that in the presence of palladium catalyst containing a water-solublephosphine such as that containing a sulfonate group, the cross-coupling reac-tion can proceed in water without copper catalyst. This was the case of the


5-iodo-2′-deoxyuridine derivative that can be coupled with a propargylic amidederivative (Equation 2.5) [20].

HN

NO

OI

R1

+ NH

N

O

R2

O

SO3Na

Ph2P 3Pd

MeCN : H2O (1 : 1), 3 h25−80 °C

HN

NO

O

R1

NH

NR2O

O

50%

(2.5)

Genet et al. [21] have used Pd(OAc)2 catalyst with simple addition of water-solublephosphine containing a lithium carboxylate functionality to perform the Sono-gashira cross-coupling in water without copper catalyst (Equation 2.6).

NHR

IR

(

CO2Li

P

NHR

R

+)

3(4 mol%)

Pd(OAc)2 (1 mol%)

MeCN : H2O (1 : 1)NEt3, 60 °C, 16−20 h (2.6)

Yang et al. [22] showed that a large variety of aryliodides with alkynes lead to theSonogashira reaction in pure water and without copper catalyst using PdCl2 catalystand pyrrolidine as a base, with high yields at 25–50 ◦C for 24 h. In the absenceof water-soluble ligand, Beletskaya [23] previously showed that the cross-couplingof alkynes with aryliodides or diaryliodonium salts can be performed in water butwith both Pd(0) and Cu(I) catalysts [24].

Several examples of sterically hindered ligands have been associated with palla-dium catalyst to promote the cross-coupling of aryl halides with alkynes in watersuch as the t-Bu-Amphos by Shaughnessy [25] or dicyclohexylaryl phosphine byBuchwald [26]. The double arylation of acetylene gas has been performed by Li[27] (Equation 2.7a) in an acetonitrile/water medium using both Pd(OAc)2/TPPTS(tris(3-sulfonatophenyl)phosphine sodium salt and Pd(OAc)2/PPh3 catalysts with-out Cu(I) catalyst. From diodoarenes, this reaction with acetylene leads topoly(aryethynylene)s [28].

The Sonogashira reaction can be performed without phosphine by using acetyltrimethylammonium bromide surfactant in a water–alcohol emulsion [23a].The use of microwave allows the reaction in water without any Cu or Pd metalcatalyst in the presence of ammonium salt and Na2CO3 as a base (Equation2.7b) [29].

2.2 Catalytic Formation of C–C Bonds from spC–H Bonds in Water 51

IR

2 + H HR

R

(a)

Pd(OAc)2/TPPTS

(2.7a)

XR

H R RR

+

(b)

Na2CO3, H2OMW, 15 min/175 °CX = Cl, Br, I

(n -Bu)4NBr

(2.7b)

The cross-coupling of alkynes with o-iodophenol has been performed for thesynthesis of benzofurans in water [30]. The most efficient catalyst appeared to bea 10% Pd/C catalyst associated with PPh3 and CuI catalyst (10 mol%) (Equations2.8a,b). These catalyst and reaction in water were successfully applied to thesynthesis of indoles [30b].

I

OHR

OR+

10% Pd/CPPh3/CuI

S-Prolinolwater, 80 °C >80%

(a) (2.8a)

O2N I

OH

I

R OR

O2N

R

+

70–75%

10% Pd/CPPh3/CuI

S-Prolinolwater, 80 °C

(b) (2.8b)

Various palladium catalysts supported on polymers have been used for the Sono-gashira reaction in water for catalyst recycling [31], such as with polymer-supportedoxime-based [32] or pyridine-based [33] ligands. Palladium catalyst grafted onmesoporous silica was also efficient in water at room temperature in thepresence of piperidine as a base [34]. Water-soluble poly(N-isopropyl)acrylamide associated to Pd-phosphine precursor allowed the cross-coupling ofalkynes with arylhalides in CH3CN/H2O medium with copper catalyst [35].By contrast, the Uozumi amphiphilic polymer-Pd(II) catalyst has been usedfor the Sonogashira reaction in water without copper additive under mildconditions [36].

For the Sonogashira reaction in water, Pd-catalysts with 2-amino-phenyldiphenylphosphinite ligand were used with NaOH under copper-free conditionsand were recyclable [37], as well as heterogeneous Pd-Schiff base complex [38].Palladium nanoparticles under ligand- and copper-free aerobic conditions inwater are used for the production of benzofurans at 100 ◦C with NEt3 as abase (Equation 2.8a) [39]. Similarly, palladium nanoparticles immobilized onsilica–starch were efficiently used for cross-coupling of alkynes and recycled


[40]. Interestingly, reticulated Pd(II)/Cu(I) cyclodextrin complexes are recyclablecatalysts for alkynylation of arylhalides in water [41].

The catalytic Sonogashira reaction in water with various catalysts is nowquite general and has found in the recent years many applications. It hasbeen applied with Pd(PPh3)4(0.2 mol%)/CuI/iPr2EtN catalytic system tothe coupling of two or three nonprotected propargylamines with di- andtriiodoarenes in water (Equation 2.9) [42]. Unprotected halonucleosides wererecently alkynylated in a water/acetonitrile mixture using Pd(OAc)2/CuI catalystassociated with a water-soluble trisulfonated phosphine ligand TXPTS (trisodiumtri(2,4-dimethyl-5-sulfonatophenyl)phosphine) (Equation 2.10) [43].

I

II

+NH2

Pd(PPh3)4, CuI, iPr2EtN

H2O, 90−100 °C, 24−48 h

H2N

NH2

NH2

75%

(2.9)

O

HO

OH

N

N

O

O

HI

+ R

Pd(OAc)2 (10 mol%)TXPTS (30 mol%)CuI (10 mol%)

Et3N (1 equiv)1 : 1 H2O/CH3CN65 °C, 30 min O

HO

OH

N

N

O

O

H

R

R = Ph, Bu, CH2CH2OH, CMe2OH (2.10)

Alkenyl iodonium salts have been used to get access stereoselectively to enynesin DMF/H2O medium with the use of PdCl2(PPh3)2/CuI catalyst and a baseat 30–40 ◦C. A large variety of enynes were obtained in good yields (Equation2.11) [44]. The same cross-coupling reaction in water was also achieved with thenickel-based catalytic system NiCl2(PPh3)2/CuI [45].

H

I+Ph(OTf)−

TfO

R1H R2

PdCl2(PPh3)2CuI HTfO

R1

R2

+DMF/waterK2CO3/NEt3

(2.11)

The efficient cross-coupling of terminal alkynes with acylchlorides in water wasdemonstrated by Li [46] to generate ynones in the presence of PdCl2(PPh3)2/CuIcatalyst (Equation 2.12). The use of a surfactant the sodium lauryl sulfate plays

2.3 Activation of sp2C–H Bonds for Catalytic C–C Bond Formation in Water 53

a key role to protect the acylchloride toward hydrolysis, and thus, ynones wereobtained with both aryl and alkyl acetylene in high yields.

R Cl

O

R′

PdCl2(PPh3)2CuI

O

R

R′Water, K2CO3/surfactant

+(2.12)

The easy deprotonation of terminal alkynes and formation of alkynyl metal inter-mediate have allowed the nucleophilic addition of alkynes to electrophiles and tothe Sonogashira cross-coupling reaction with heteroarene halides to be performedin water-solvent or pure water, as very general reactions.

2.3Activation of sp2C–H Bonds for Catalytic C–C Bond Formation in Water

The activation of an sp2C–H bond is much more difficult to achieve than thatof an spC–H bond as it cannot be easily deprotonated by a base, even if thedeprotonation of (hetero)arene sp2C–H bond has recently been demonstrated byt-BuOK or t-BuONa to promote the cross-coupling reaction with arylhalides withoutany metal catalyst [47]. The first examples of sp2C–H bond functionalization bymetal catalysts were performed via an electrophilic substitution with a high valentmetal catalyst, usually operating in acetic or trifluoroacetic acid as solvent [48].More recently, evidence has been brought for the sp2C–H bond activation viadeprotonation by intramolecular cooperative assistance of the metal site and acoordinated basic ligand such as carbonate or carboxylate [4, 7]. The activationwith metal catalyst assisted by acetate base or ligand offers an autocatalytic processaccelerated by the generated acetic acid and which may explain its profitable useas solvent [49]. The C–H bond deprotonation process is quite compatible to betolerated by water. However, the first examples of sp2C–H cross-coupling reactioninvolving water were actually explored using water as additive to a solvent. This isonly recently that catalytic sp2C–H bond functionalization for C–C bond formationcould be performed in water only as solvent using mainly palladium and rutheniumcatalysts.

2.3.1Homocoupling of sp2C–H Bonds

There are several examples of arene sp2C–H bond activation in water without C–Cbond formation. As a representative example, pincer rhodium complexes havebeen shown to catalyze the H/D exchange between arene and water (Equation 2.13)[50]. This demonstrated the C–H bond activation of non functionalized benzene inwater by Rh(I) catalyst and suggested the formation of Rh-C6H5 intermediate. It isnoteworthy that only sp2C-D bonds are activated from C6D5CD3 and H2O withoutdiphenyl formation [50a].


D

D

D

D

D

D+ H2O

N−RhX

PtBu2

PtBu2

100 °Cd6−xhx + H(D)O

X = OAc, OPh, OC6H4NO2

(2.13)

The early examples of catalyzed sp2C–H bond functionalization with water ad-ditive involved oxidative homocoupling of arenes and biaryl formation duringoxidation processes [9]. Oxidation of arenes with oxygen in the presence ofPd(OAc)2/H5[PMo10V2O40] redox system in biphatic medium (arene/AcOH–H2O)led selectively to the formation of biaryl derivatives (biphenyl and bitolyl) [51].The oxidation of benzene with oxygen in the presence of the catalytic sys-tem Pd(OAc)2/H3PMo12O40/AcOH:H2O (2 : 1) led to the selective formationof biphenyl (19% yield, 100% selectivity at 130 ◦C) [52]. The oxidative cou-pling of benzene into biphenyl was also promoted during oxidation in air byPdCl2/M(OAc)n catalytic system in AcOH/AcONa, and the addition of water wasshown to increase the selectivity in biphenyl formation [53]. The dehydrogenativehomocoupling of arenes into biaryl derivatives on oxidation with a variety of metalcatalysts is a general phenomenon when oxygenation of the arene does not takeplace [54].

The ruthenium-catalyzed homocoupling of phenols in water has been performedusing a heterogeneous catalyst Ru(OH)x/Al2O3 [55]. This catalytic system hasbeen especially used for the synthesis of binaphtol from naphtol, as it allowshomocoupling selectively at ortho positions (Equation 2.14). The solid catalystcan be recycled several times. The homocoupling is suggested to arise from thecoupling of two radicals generated by oxidation with ruthenium catalyst that isreoxidized by oxygen [55].

OH

ROH

OH

R

R

Ru(OH)x /Al2O3

O2 (1 atm)/water100 °C, 4−5 h

80−99%

(2.14)

Stoichiometric amount of FeCl3·6H2O in water has been used for the oxidation ofphenols into biphenols and diphenoquinones with coupling at the para positionswhen ortho positions were protected (Equation 2.15) [56].


OH

FeCl3·6H2O

OH

OH

O

O

water (30 mL), 50 °C, 4 h

19%

+

68%(2.15)

By contrast, the oxidation of dialkylarylamines in water with H2O2 in the presenceof CuBr (1 equiv) leads to para C–H bond homocoupling and the efficient formationof benzidines under very mild conditions (Equation 2.16) [57].

N

R1

R2

NNR1

R2

R1

R2

CuBr (1 equiv)H2O2 (10 equiv)

Water, 0−25 °C, 10 h50−76% (2.16)

The same reaction can be performed in water but using the one-electron oxidantcerium(IV) ammonium nitrate (CAN) at room temperature. The benzidines areobtained after 2 h at room temperature, in 60–85% yields [58]. The mechanismis based on a one-electron oxidation and homocoupling of C(4) centered radicalfollowed by deprotonation [58].

2.3.2Direct C–H Bond Arylation of Alkenes and Aryl Boronic Acid Derivatives

The addition of boronic acids to unactivated alkenes such as styrylolefins in waterwith [RhCl(COD)]2 catalyst and a water-soluble phosphine PPh(p-C6H4SO3K)2

(TPPDS) and P(m-C6H4SO3Na)3 (TPPTS) allowed the formal arylation of sp2C–Hbonds but via the Heck-type reaction in the presence of a phase transfer agent(SDS) at 80 ◦C for 15 h (Equation 2.17a) [59].

PhArB(OH)2

[RhCl(COD)]2 (2 mol%)TPPDS (8 mol%)

Ph

Ar

+Na2CO3, SDS, H2O , 80 °C

(2.17a)

[RhCl(COD)]2 (2 mol%)TPPDS (8 mol%)

+ ArB(OH)2N N ArNa2CO3, SDS, H2O, 80 °C

(2.17b)

By contrast, when a heteroaromatic olefin was used, such as 2-vinyl pyridine,addition/hydrolysis took place affording the arylated saturated products undersimilar conditions (Equation 2.17b) [59].


2.3.3Cross-Coupling Reactions of sp2C–H Bonds with sp2C-X Bonds in Water

2.3.3.1 Direct C–H Bond Arylations with Aryl Halides and Palladium CatalystsThe cross-coupling reaction between aryl halides and heteroarenes, via C–H bondfunctionalization in the presence of Pd(0) catalysts, undergoes arylation at themost electron-rich 2- or 5-position through a possible SEAr mechanism [60, 61].However, it required harsh conditions in organic solvent (140 ◦C in DMF) withPd(OAc)2/phosphine catalyst [60].

While the Suzuki–Miyaura reaction does not easily occur in water, Gre-aney [62] first showed that direct arylation of heterocycles with aryliodidescould be performed in water under rather mild conditions. A large varietyof 5-arylated 2-phenyl thiazoles were obtained by direct reaction of thiazoleswith aryl iodides in water in the presence of PdCl2(dppf)/PPh3 catalytic system(dppf, 1,1′-ferrocenebis(diphenylphosphine)) with inorganic base Ag2CO3 (2 equiv)(Scheme 2.1). Excellent yields were obtained (80–99%), and in each case, the cata-lyst was more efficient in water than in acetonitrile, THF, dioxane, or methanol, oreven when running the reaction neat. For some substrates, the reaction conditionscan be decreased to 60 ◦C for 6 h only in water.

Ar-IN

S PhH

HN

S PhAr

H

N

S PhCl

N

S Ph

F N

S PhBr

N

S PhN

N

S PhN

N N

S Ph

HO

+

[Pd(dppf)Cl2]·CH2Cl2,PPh3, Ag2CO3, 60 °C

MeCN, 72 h, orwater, 24 h

95% 82% >99%

71% >99% 81%

N

SO2N OMe

N

SCl CF3

91%>99%

Scheme 2.1


With thiazoles containing functional aryl group (p-CF3, p-MeO) at 2-position, thearylation ‘‘on water’’ is consistent with SEAr mechanism, although the concertedmetalation deprotonation (CMD) cannot be eliminated (Scheme 2.1) [62].

The arylation on water (24 h, 60 ◦C) has been applied to several heterocycles andled to cross-coupling products in good yields (Equation 2.18). These reactions onwater tolerate a large variety of functional groups.

Ar1−I Het −H Ar1 Het+

[Pd(dppf)Cl2]·CH2Cl2,PPh3, Ag2CO3, 60 °C

Water, 24 h (2.18)

N

S

Cl

Cl

N

SAc N

OS OMe

83% 70% 79% 82%

Greaney [63] has also shown that 2-aryloxazoles, easily prepared by Negishicross-coupling reaction of oxazoles with aryl iodides, are easily regio selectively ary-lated at the C5-position with a variety of electron-rich or electron-poor aryl iodides,with the same Pd(II) catalyst precursors in the presence of 2 equiv of Ag2CO3 onwater (Scheme 2.2).

This C–H cross-coupling reaction on water has been applied to the synthesis ofplant natural products balsoxin and texaline (Equations 2.19a,b) [63].

I

R2

O

N

R1

R2

N O

R1

O

N

R1 CF3

O

N

R1

NO2

O

N

R1 Br

O

N

R1

O

Me

+

[Pd(dppf)Cl2]·CH2Cl2 (5 mol%),PPh3 (10 mol%), Ag2CO3, 60 °C

water, 24 h

R1 = H

R1 = OMe

R1 = CH3

80%

98%

90%

84%

85%

80%

68%

83%

70%

86%

89%

93%

R1 = H

R1 = OMe

R1 = CH3

Scheme 2.2


O

N

MeO

MeO

N O84%

Balsoxin (2.19a)

O

N

N

O

O

N O

N

74%

Texaline (2.19b)

The same method was used for the C2 direct arylation of 5-substituted oxazoleswith aryl iodides in water at 60 ◦C (Scheme 2.3) [64], and it offered the directaccess to a large variety of heterocycles by making aryl–heteroaryl or bi(hetero)arylbonds.

This synthetic strategy has allowed the access to trisoxazole derivatives, fromthe 4-ethyl carboxylate oxazole [64], by two successive heteroarylation with2-triisopropyl silyl-4-iodo oxazole and deprotection. However, in this case, theHermann–Beller palladacycle (HBP) [65] in toluene rather than in water waspreferable (Equation 2.20).

Ar−IN

O RH

N

O RAr

N

O Ph

S

N

O PhEtO2C

N

OMeO

Cl

N

O CO2EtMe

N

O CO2EtNC

+

PdCl2(dppf)·CH2Cl2 (5 mol%)Ag2CO3 (2 equiv)PPh3 (10 mol%)

R = PhR = (2-Cl)C6H4R = CO2Et

Water, 60 °C, 16 h

66% 80% 89%

67% 48%

Scheme 2.3


+N

OTIPS

(1) HBP, Cs2CO3,toluene, 110 °C, 16 h(2) aq TBAF, rt,5 min

71%I

N

OH

CO2EtN

O

O

NH

CO2Et

(1) HBP, Cs2CO3,toluene, 110 °C, 64 h(2) aq TBAF, rt.5 min

51%

O

NON N

O

H CO2Et

N

OTIPS

I

(2.20)

The direct arylation of 2H-indazoles with both aryl iodides and bromides has beensuccessfully performed by Greaney [66] with Pd(II) catalyst precursor in wateras previously described for thioxazoles and oxazoles (Scheme 2.4). Analogously,various 2H-substituted indazoles, with different N-aryl groups, have been arylatedwith aryliodides at 50 ◦C for 16 h in water.

NN

H

Y

X

RN

N

YR

NN

NO2

NN

N

NN

MeO

+

[Pd(dppf)Cl2]·CH2Cl2 (5 mol%)PPh3 (10 mol%)Ag2CO3

Water, 16 h, 50 °C

X = Br/IY = CH/N

86%(ArBr)

95%(ArI)

81%(ArI)

Cl

R = p-Br, p-Me, p-CO2Et

Scheme 2.4

Interestingly, Lipshutz [67] has recently demonstrated that sp2C–H bonds ofanilides can be arylated with aryl iodides with palladium catalyst in water, at roomtemperature, in the presence of a surfactant (Equation 2.21). The reaction is per-formed with Pd(OAc)2 (10 mol%) with 2 equiv of AgOAc in 2 wt% surfactant/waterwith HBF4 (5 equiv). For this ortho monoarylation of aromatic ureas, the commer-cially available Brij 35 (polyoxoethylene (23) lauryl ether) appears to be an efficient


micelle-forming amphiphile in water. The limitation of this reaction in water arisesfrom the use of sterically hindered substrates or from electron-deficient ureas.These conditions contrast with those of the classical cross-coupling of anilidesin organic solvents that take place above 100 ◦C and suffer from partial doublearylation [68].

HN N

OR

+

I

R′2 euiqv

Pd(OAc)2 (10 mol%)

AgOAc (2 equiv)HBF4 (5 equiv)2% Brij 35Water, rt

HN N

OR

R′

R′ = H, Me, OMe

(2.21)Electron-rich aryl iodides lead to higher yields of bisaryl derivatives. The posi-tive influence of HBF4 with Pd(OAc)2 catalyst is explained by the formation ofcationic Pd(II) species, as the Pd(OAc)2/AgBF4 catalytic system can be effectivewithout addition of HBF4. The use of other surfactants such as polyoxyethanylα-tocopheryl sebacate (PTS) or TPGS-750-M associated to the same catalyst systemPd(OAc)2/AgOAc/HBF4 leads to the C–H bond cross-coupling products in similaryields [67].

After cross-coupling reaction, in situ regioselective bromination or nitration of di-aryl derivatives can be achieved illustrating the tandem C–H arylation/electrophilictrapping under organic solvent-free conditions (Scheme 2.5) [67].

HN

NMe2

O

H

OMe

OMe

I

HN

NMe2

O

O2N

OMe

OMe

HN

NMe2

O

Br

OMe

OMe

+

Pd(OAc)2AgNO3, HBF42% Brij 35

(1) Pd(OAc)2AgOAc, HBF4

(2) Br22% Brij 35

48%

70%

Water, rt

Water, rt

Scheme 2.5


Recently, Djakovitch et al. [69] have reported a remarkable site-selective C2 andC3 arylation of indoles ‘‘on’’ water, with palladium catalyst. They showed that thisregioselectivity is base- and halide-controlled C–H arylation of (NH)-indoles inwater. The arylation at C2-position of arylindoles with aryl iodides was performedwith 5 mol% Pd(OAc)2 in the presence of 5 mol% bis(diphenylphosphino)methane(dppm) and 3 equiv of KOAc at 110 ◦C on water for 24 h. Good yields were obtained(48–79%), and excellent regioselectivities (up to 99 : 1) were observed. Thismethodology tolerates both electron-donating and electron-withdrawing groups(OMe, Cl, naphthyl, and Ac) (Scheme 2.6a) [69].

When the base LiOH·H2O was used instead of AcOK and aryl bromides wereused as the arylating reagent, the C3-arylindoles are selectively obtained in 69–91%yields. With substituted indoles at 4-, 5-, and 6-positions and 2- and 4-substitutedaryl bromide functional groups (OMe, Cl, and CF3), the C3 arylation could beperformed in water (Scheme 2.6b).

Obviously in this case, the selection of base and halide is the key to controlC2 versus C3 arylation. The influence of KOAc is believed to favor CMD at the

NH

R1

Br

R2NH

R1

R2

+Pd(OAc)2/dppm (5 mol%)LiOH·H2O (3 equiv)

H2O, 110 °C, 24 h

(C3 >> C2)

R1

NH

I

R2

NH

NH

Cl

NH

OMe

NH

R1

NH

MeO

NH

NH

Ac

R2

Pd(OAc)2/dppm (5 mol%),AcOK (3 equiv)

Water, 110 °C, 24 h

75%(22 : 1)

67%(18 : 1)

71%(20 : 1)

77%(18 : 1)

66%(4 : 1)

79%(>99 : 1)

+

(C2 >> C3)

(a)

(b)

Scheme 2.6


C2-position with intramolecular acetate promoted C2-H bond deprotonation. Bycontrast, bromide additive and hydroxide base (LiOH·H2O) favor C3 arylation thatis suggested to result from a C3 electrophilic palladation pathway followed by OH−

promoted deprotonation.

2.3.3.2 Direct C–H Bond Arylations with Aryl Halides and Ruthenium CatalystsFor the cross-coupling of C–H bonds with aryl halides, the ruthenium(II) promotedsp2C–H bond activation is based on direct C–H bond deprotonation with theassistance of a coordinated or an external base [3d, 4, 7, 49], such as carbonate[4a], acetate [4b], or other carboxylates [3d, 70], to generate first a metalacycle thatis the site for further oxidative addition of aryl halides. As ruthenium(II) catalystsoperating in water are stable [6], it was attractive to directly perform arylationof (hetero)arene C–H bonds with arylhalides and ruthenium(II) catalysts in thepresence of a reversibly coordinating base.

Thus using 2-phenyl pyridine with 2.5 equiv of phenyl chloride in water withoutany surfactant, the [RuCl2(p-cymene)]2/4 KO2CR catalytic system led at 100 ◦Cfor 2 h to a complete ortho arene diarylation [71]. Diarylation was reached usingKOPiv (potassium pivalate) (2 equiv/ruthenium) as the reversibly coordinatingbase, whereas the base/ligand KOAc and K2CO3 led to a less active associationbetween the ligand and metal catalyst. The reaction can take place at 60 ◦C andeven at room temperature for longer reaction times. The efficiency of added base isin the sequence K2CO3 > KHCO3 > K3PO4 and for phenylhalides, PhCl > PhBr> PhI, corresponding to their solubility sequence in water (Equation 2.22) [71].

N

Cl

N N

K2CO3

KOAc

KOPiv

KOPiv (60 °C)

+ 2

[RuCl2(p-cymene)]2 (5 mol%)KO2CR (20 mol%)

K2CO3(3 equiv),water, 100 °C

+

Entry Additives Time (h) Conv. (%) Ratio (mono:di)

1 2 97 21 : 79

2 2 100 26 : 74

3 2 100 0 : 100

4 24 100 9 : 91 (2.22)

It is noteworthy that the above-mentioned catalytic system operates with arylchlorides that are the cheapest and most accessible aryl halides but are usuallythe less reactive with palladium catalysts. This ruthenium(II) catalyst is also moreefficient in water than in NMP (N-methyl pyrrolidone) or diethylcarbonate underentry-3 conditions (2 h, 100 ◦C) (Equation 2.22); 100% conversion was obtainedwith mono/diarylation product ratio – 0 : 100 (water) [71], 25 : 75 (NMP) [46], and45 : 55 (diethylcarbonate) [72]. The in situ prepared catalyst is only slightly less


N Het−X N

Het

N

Het

Het

N

S

SN

S

S NNN

NN

S

S NN

S

S

N

+

[RuCl2(p−cymene)]2 (5 mol%)KOPiv (20 mol%)

K2CO3 (3 equiv),water, 100 °C, 10−20 h

+

89% 92% 41%

90% 95% 83%

Scheme 2.7

efficient than the isolated [Ru(OPiv)2(p-cymene)] complex, and it is preferable touse the in situ prepared catalyst in water.

The Ru(II)-catalyzed reaction can be exploited to produce tridentate ligands byreaction of phenyl pyridine or N-phenyl pyrazole in water at 100 ◦C but for longerperiod of time (10–20 h) to produce tris-1,2,3-heteroarylbenzenes. Monoarylationof benzoquinoline is also efficiently performed in water (83%) (Scheme 2.7) [71].

The easy arylation with aryl chlorides in water was successfully applied to1,3,5-trichlorobenzene, which led to tridentate ligands. The trispyridine moleculewas obtained in 77% yield after 36 h at 100 ◦C (Equation 2.23) [71], whereas it isproduced in 45% yield in NMP at 150 ◦C for 24 h [73]. The trisbenzoquinolinemolecule was obtained in 45% yield after 36 h (40% in NMP at 150 ◦C for 24 h) [71].

Cl

Cl

Cl

N

N N

N

[RuCl2(p -cymene)]2 (5 mol%),KOPiv (20 mol%),K2CO3(3 equiv),H2O, 100 °C, 36 h

1 equiv

3.2 equiv

77% (2.23)


Previously, the diarylation of phenylpyridine with PhCl [73] was obtained in 61%yield using 2.5 mol% [RuCl2(p-cymene)]2, with preligand Ad2P(O)H (10 mol%) inan organic solvent containing water: NMP/H2O (2 ml/1 ml) at 120 ◦C for 20 h.This crucial experiment showed that water tolerated the ruthenium(II) C–H bondactivation catalyst. It is also noteworthy that pure NMP solvent allowed to reachhigher diarylated product yield 72% (5 h) or 98% (24 h) than the mixture NMP:H2O(61%) (Equation 2.24).

N

PhCl

PH

O

NMP

NMP:H2O (2 : 1)

NMP

N

PhPh+

[RuCl2(p -cymene)]2 (2.5 mol%)

L (10 mol%), K2CO3, NMP, 120 °C

Ligand L Time (h) Yield (%)

5

20

24

Solvent

72

61

>98 (2.24)

Water was recently shown to modify the regioselectivity of the ruthenium(II)-catal-yzed alkylation of 2-(p-MeOC6H4)pyridine with hexylbromide [74]. The use ofMesCO2H as cocatalyst with [RuCl2(p-cymene)]2 in NMP led to the expected orthoalkylation with respect to pyridine. By contrast in water, as in neat conditions, asmall amount of the meta-alkylated product (7%) was formed (Equation 2.25).

N

OMe

H

H

N

OMe

Hex

H

N

OMe

H

Hex

+ n-HexBr

[RuCl2(p -cymene)]2 (2.5 mol%)RCO2H (30 mol%)

Solvent, K2CO3, 100 °C

+

MesCO2H, NMP: 48 % ---

MesCO2H, H2O:

MesCO2H, neat:

45 % 7 %

40 % 6 %(2.25)

2.3.4Cross-Coupling Reactions of sp2C–H Bonds with Carbon Nucleophiles in Water

While organic solvents allow intermolecular arene C–H bond functionalizationwith carbon nucleophiles, water has been shown to inhibit this process [75]. Mixed


alkyl and aryl palladacycle intermediates have been observed to result from C–Hbond activation using norbornene insertion [76] or without it [77]. Jia et al. [75]have recently shown that the palladium-assisted formation of intramolecular Heckinsertion product in DMF could lead to the arene C–H bond functionalizationwith formation of (arene)C–CN, C-aryl, and C–CH=CHR bonds on reaction withnucleophiles (MCN, ArB(OH)2) or with olefin (Equation 2.26, path B). However, ina mixture DMF/H2O (95 : 5) under the same condition, the C–C bond formationinvolves the terminal alkene carbon. Thus, in this case, water inhibits the arene C–Hbond functionalization likely by destructing the pallacycle intermediate (Equation2.26, path A).

Pd(OAc)2 (5 mol%)Na2CO3 (1 equiv)TBAC (1 equiv)

DMF, 60 °C XY

Nu

90%

CO2Et

CO2Et

CO2Me

O

74%

OMe

XY

I

+


DMF/H2O (95 : 5), 60 °CXY

Nu

O

CN

88%O

78%

OMe

Path A PathB


DMF, 60 °C XY

Nu

90%

CO2Et

CO2Et

CO2Me

O

74%

OMe

XY

I

+

K4[Fe(CN)6]·3H2O (2.2 equiv)or olefin (1.3 equiv)or RB(OR2)2 (1.3 equiv)


DMF/H2O (95 : 5), 60 °CXY

Nu

O

CN

88%O

78%

OMe

Path A PathB

(2.26)The mechanism of this reaction is consistent with the intramolecular Heck-typeinsertion product followed by a five-membered palladacycle via intramolecularC–H bond deprotonation before being trapped by cyanation or the Heck or theSuzuki reagent. Water is the key to control the regioselective cleavage of the arenecarbon–palladium bond of the resulting palladacycle by cyanation or the Heckor the Suzuki reaction. It rather leads path B to the alkyl-functionalized product(Scheme 2.8).

2.3.5Oxidative Cross-Coupling of sp2C–H Bond Reactions in Water

2.3.5.1 Alkenylations of Arenes and Heteroarenes with Palladium CatalystsAnother attractive way to make C–C bonds from sp2C–H bonds consists inthe oxidative dehydrogenative cross-coupling reaction from two different sp2C–Hbonds (Equation 2.27). The first example was reported by Fujiwara and Moritani inthe alkenylation of arenes [48].

C1 H C2 H C1 C2Oxidant (-2H)

+(2.27)


Pd(0)

O

HPd

LO O−

O

O

Pd

O O−

OH

O

Nu H

O

Pd H

Nu

O

PdNu

H

O

NuH

Nu

No H2Opath B

O

ICO3

2−

Nu

H2Opath A

Scheme 2.8

De Vries and Van Leeuwen [78] showed the dehydrogenative coupling of acrylatewith anilides in the presence of Pd(OAc)2 catalyst and benzoquinone (BQ) asoxidant in AcOH (54%) or better in AcOH/Toluene/TsOH additive (72%) atroom temperature (Equation 2.28). Thus, the NHCOMe group directed the C–Hactivation at the ortho position. The addition of water (5% v/v) instead of TsOHdecreased the yield to 49%; however, it was shown that the reaction tolerated water.

HN

O+ CO2n -Bu

Pd(OAc)2BQ

AcOH/Toluene+ TsOH (72%)+ H2O (5% v/v) (49%)

HN

O

CO2n -Bu

(2.28)The similar reaction of butylacrylate with anilides bearing not only a meta-chloridebut also an activating para-donating group (Me, OMe) in the presence of Pd(OAc)2

and BQ/TsOH·H2O (1 equiv) at room temperature was performed by Prasad et al.[79] and led to ortho-alkenylated anilides in 25–80%.

Yamada and Ishii [80] performed the alkenylation with acrolein of benzene,alkylbenzenes, using Pd(OAc)2 with H4PMo11VO40·26H2O catalyst and oxygen as


oxidant in propionic acid (Equation 2.29). No directing group was required and thereaction tolerated water. The alkenylation with methacrolein and cinnamaldehydewas also possible [80].

R + O

Pd(OAc)2 (0.1 mmol)H4PMo11VO40·26H2O (0.02 mmol)

Na2CO3 (0.05 mmol),EtCO2H (5 ml),90 °C/1.5 h

R = H, Me, t-Bu, OMe...

O

R

(2.29)

These examples showed that palladium-catalyzed oxidative dehydrogenative alkeny-lation of arenes tolerated water. Lipshutz has reported the first example of catalyticFujiwara–Moritani [48] alkenylation reaction by cross-coupling of two differentC–H bonds, between anilides and a functional alkene in water as solvent, but inthe presence of a surfactant [81].

The reaction is performed with anilide and acrylate in the presence ofPd(OAc)2/1,4-benzoquinone and AgNO3 with 5 equiv of HBF4 in water orpreferably with cationic catalyst [Pd(MeCN)4](BF4)2 without HBF4 [81]. In bothcases, the reaction requires the presence of a surfactant such as PTS but takesplace at room temperature, and a large variety of functional alkenes are produced.The amide group directs the ortho C–H bond alkenylation, and the reactionleads only to a monoalkenylated product (Scheme 2.9). The association of theTPGS-750-M surfactant to the same catalyst system in water leads to similarresults [82].

The mechanism of this alkenylation is consistent with a cyclometalation via orthoC–H bond deprotonation, followed by the Heck-type insertion/β-elimination. The

R1 H

NHAc

+CO2R2

[Pd(MeCN)4](BF4)2 (10 mol%)BQ (1equiv), AgNO3 (2 equiv) R1

NHAcCO2R2

MeO

NHAcCO2

Et

76%

MeO

HN

80%

O

CO2(CH2)11CH3

MeO

HNO

CO2

MeOEt

89%

MeO

HNO

CO2

80%

OMe

2 wt% PTS/H2O (1 ml)rt, 20 h

Scheme 2.9


Pd2+

R′O

HNO

Pd+H

HR′O

HNO

R′O Pd+

HNO

HPd+

CO2R

R′OCO2R

HNO

H+

Oxidant

H+

Pd(0)

Scheme 2.10

BQ has the role to reoxidize the Pd(0) into active Pd(II) species (Scheme 2.10)[81].

2.3.5.2 Alkenylation of Heterocycles Using In(OTf)3 CatalystThe development of CDC methodology to construct C–C bonds from two differentsp2C–H bonds has been applied by Li [83] for the coupling of benzoquinone BQsp2C–H bonds using In(OTf)3 in water. First, the reaction of electron-rich areneswith 1,4-benzoquinones in the presence of In(OTf)3 (5 mol%) in water at roomtemperature to give high yields of aryl-substituted BQs (Scheme 2.11) [84].

Ar−H +

O

O

R In(OTf)3, 5 mol%

H2O, rt

O

O

R

Ar

+

O

O

R Ar

O

O

NMe2

OMe

93%

O

O

NMe2

69%

O

O

N

63%

Me O

O

64%

OMe

Scheme 2.11


It is noteworthy that when this reaction was performed in acetonitrile,dichloromethane, or THF, low yields of products were obtained and that wateras a solvent promotes the reaction. The reaction is expected to proceed viathe Friedel/Crafts-type conjugate addition reaction of the In(III)-activated BQ,followed by BQ oxidation of the resulting 1,4-dihydroxybenzene.

By contrast, the CDC coupling of BQ with indole derivatives in water at roomtemperature was performed without any catalyst (Equation 2.30) [85]. The reactionwas regioselective and the C–C coupling occurred with indole C3-H bond and wasshown to be accelerated by water solvent, with respect to CH2Cl2, CH3CN, THF, ortoluene, and bis(indolyl)-1,4-benzoquinones could be reached easily in water [85].

N R2+

O

O

X

X

X = H, Cl

Waterrt

R

N R2R

O

O

X

X

R = H, alyl

R1

R1

(2.30)

2.3.5.3 Alkenylation of Arenes and Heteroarenes with Ruthenium(II) CatalystsAfter the pioneer work of Yi [86] on ruthenium-catalyzed alkenylation of sp2C–Hbonds of arylketones and benzamides, Satoh and Miura [87] have recently shownthat heterocycles containing a carboxylic directing group could be alkenylated using[RuCl2(p-cymene)]2catalyst with excess of oxidant Cu(OAc)2·H2O in DMF. Inter-estingly, this reaction takes place without decarboxylation as palladium catalystsusually do [88]. A dehydrogenative cross-coupling reaction gives access in onestep to alkenylated indole, thiophene, pyrrole, and furan derivatives retaining the(heterocycle)carboxylate group (Equation 2.31).

YCO2H CO2Bu

YCO2Me

CO2Bu

+(1) [Ru(p-cymene) Cl2]2 - 2 mol%

Cu(OAc)2 (2 equiv),LiOAc (3 equiv),DMF, 80 °C, 6 h

(2) MeI

K2CO3

(2.31)

Ackermann and Pospech [89] soon after using a similar catalytic system[RuCl2(p-cymene)]2/Cu(OAc)2·H2O showed that alkenylation of benzoic acidderivatives with alkylacrylate could be performed in water, via an oxidativedehydrogenative process without decarboxylation, and that carboxylate could insitu add to the generated double bond leading to the intramolecular Michaeladdition product. This catalytic reaction in water shows the directing ability of thecarboxylate group by alkenylation at the neighboring C–H bond and constitutes anexcellent synthetic method of annulated lactones from aromatic carboxylic acids in


water (Equation 2.32) [89]. In DMF solvent, this synthesis was not obtained [88].

ROH

O

CO2R

O

O

R1

O

O

R1

F

R

O

O

R1

OMe

MeO

O

O

CO2R

+

[Ru(p -cymene) Cl2]2 - 2 mol%Cu(OAc)2.H2O (2 equiv)

Water, 80 °C,16−24 h

R1 = CO2Bu : 90%

R1 = CN : 95%

R1 = CO2Bu : 66%

R1 = CN : 81%R1 = CO2Et : 75%

R1 = CN : 76%

(2.32)

This cross-dehydrogenative C–H bond coupling takes place with a variety ofacrylates and benzoic acids with 2 equiv of Cu(OAc)2 · H2O in water at 80 ◦C for16–24 h. It is applicable to acrylonitrile. This coupling appears to be an irreversibleprocess as from D-labeled benzoic acid, the reaction proceeds without benzeneH/D exchange in water, with a kinetic isotope effect of kH/kD = 3.6 [89].

Ruthenium(II)-catalyzed oxidative annulations of benzamides with alkynes ac-companied by both ortho C–H and N-H bond cleavage to generate isoquinoloneswere demonstrated by Ackermann [90], using a similar [RuCl2(p-cymene)]2/Cu(OAc)2·H2O catalytic system operating efficiently in t-AmOH (Equation 2.33).

NH

O

R1

R2 R3 R4 N

O

R1

R3

R4R2+

[RuCl2(p -cymene)]25 mol%

Cu(OAc)2 . H2Ot -AmOH, 100 °C, 22 h

(2.33)

This catalytic system was modified to be operative in water and was applied to thesynthesis of indoles from anilines N-protected with a 2-pyridyl and 2-pyrimidylgroup. This coordinating group linked to nitrogen is essential for the reactionto take place. In this case, the modified ruthenium(II) catalyst is based on[RuCl2(p-cymene)]/4 KPF6 to favor the formation of cationic Ru(2+) species inwater. This oxidative dehydrogenative process requires the use of Cu(OAc)2·H2Ooxidant as well (Equation 2.34) [90]. A large variety of indole derivatives wereproduced leading to free indoles on treatment with NaOEt in DMSO.


R1

+

R2

R3

[RuCl2(p-cymene)]2 (5.0 mol%)KPF6 (20 mol%)

Cu(OAc)2·H2Owater, 100 °C, 22 h

NH

X N

X = CH or N

R1

N

X N

R2

R3

(2.34)

The reaction is faster with diarylacetylenes than with dialkylacetylenes and isregioselective with alkylarylacetylenes as the nitrogen atom binds selectively to thealkyne carbon linked to the aryl group. The reaction is favored by electron-donatinggroup (p-OMe vs p-F) (Equation 2.35) [90].

+[RuCl2(p-cymene)]2 (5.0 mol%)KPF6 (20 mol%)

Cu(OAc)2.H2Owater, 100 °C, 22 h

NH

N N

X = CH or N

Me

n -C4H9

OMe

n-C4H9

F

N

N NMe

n-C4H9

OMe

63%

+

N

N NMe

n-C4H9

F

29% (2.35)

A proposed mechanism is based on initial coordination of the 2-pyrimidyl group tothe Ru-OAc moiety followed by aryl C–H bond deprotonation by the coordinatedacetate.

Li and Wang [91] have recently shown the oxidative dehydrogenative annulationsof benzamides with alkynes into isoquinolones using benzamides with oxidizingN-methoxy group. This methoxy group associated to the previously used catalyticsystem for CDC [RuCl2(p-cymene)]2/Cu(OAc)2·H2O (2 equiv), but with 20 mol%NaOAc in methanol, allows this catalytic reaction to be performed at roomtemperature (Equation 2.36).

N

O

OMe

HR3

R1 R2 N

O

OMe

R2

R1R3+

[RuCl2(p -cymene)]23 mol%

NaOAc (20 mol%)MeOH (0.2 M), 8 h (2.36)

Ackermann [92] with the same N-methoxy benzamides but by modifying thecatalyst has shown that this addition of alkynes leading to isoquinolones can be


performed in water. The catalyst [RuCl2(p-cymene)]2 is associated to KO2CMes(30 mol%) to operate at 60 ◦C in water (16 h), whereas KPF6 additive was this timenot operative (Equation 2.37a).

NH

O

OMe

R1

Ph

Ph

NH

O

Ph

Ph

R1

NH

O

Ph

PhMeO

NH

O

Ph

PhF

+

[RuCl2(p -cymene)]2 (2.5 mol%)KO2CMes (30 mol%)

H2O, 60 °C, 16 h

63% 72%

NH

O

n -Pr

n -PrF

NH

O

Et

Ph

65% 83% (2.37a)

+

n -Pr

n -Pr

[RuCl2(p-cymene)]2 (2.5 mol%)KO2CMes (30 mol%)

H2O, 60 °C, 16 h

NH

O

Ph

Ph

Ph

Ph

+NH

O

n -Pr

n -Pr

a b

NH

O

OMe

55%; a/b = 6/1 (2.37b)

As for ruthenium(II)-catalyzed isoquinoline syntheses, C–H bonds nonstericallyhindered by a neighbor substituent and associated with electron-withdrawinggroups favor the reaction that is faster with diarylacetylenes (Equation 2.37b).

This reaction can be applied to free hydroxamic acid under slightly more drasticconditions at 60–100 ◦C for 16 h in water (Equation 2.38) [92].

NH

O

OH

R1 +

R2

R3

[RuCl2(p-cymene)]2 (5.0 mol%)KO2CMes (30 mol%)

Water, 60−100 °C, 16 h

NH

O

R1

R2

R3

(2.38)

The cross-dehydrogenative alkenylation of benzamides with ruthenium catalyst wasrecently performed in organic solvent by using [RuCl2(p-cymene)]2 catalyst [93].Now, the Ackermann’s group has succeeded to perform this catalytic monoalkeny-lation reaction in water using the noncoordinating salt KPF6 (20 mol%) in thepresence of Cu(OAc)2·H2O as oxidant (1 equiv). The catalytic reaction can beperformed under air with catalytic amount of oxidant but with reduced efficacy. It


HN R3

O

+ CO2R2

R1

[RuCl2(p-cymene)]2 (5.0 mol%)KPF6 (20 mol%)Cu(OAc)2·H2O

Water, 120 °C, 20 h

HN R3

O

R1

CO2R2

HN Me

O

CO2Et

F74%

HN Me

O

CO2n−Bu

Me55%

HN Me

O

CO2Et

66%

Cl

Scheme 2.12

is noteworthy that the catalytic system is more active in water than in DMF, NMP,and t-AmOH (Scheme 2.12) [94].

The reaction is favored by electron-rich anilides. The regioselectivity of alkeny-lation of the aryl group linked to the carbonyl group of anilide is demonstrated(Equation 2.39).

+ CO2R2

[RuCl2(p-cymene)]2 (2.5−5.0 mol%)KPF6 (20 mol%)Cu(OAc)2.H2O

Water, 120 °C, 20 h

NH

O

R1

NH

O

CO2Et

46%

NH

O

CO2Et

47%

FR

(2.39)The monoalkenylation of a variety of heterocycles such as indoles, thiophenes,benzofurans and directed by the MeNHCO functional group linked to the arenewas achieved in water under similar conditions (Scheme 2.13) [94].

2.4Activation of sp3C–H Bonds for Catalytic C–C Bond Formation in Water

2.4.1Selective sp3C–H Activation of Ketones

The synthesis of transition-metal complexes via sp3C–H bond selective activa-tion is an important method in synthetic applications for the understanding of


N

NH

MeO

Me

CO2Et

52%

X

HN−Me

O

+ CO2R

[RuCl2(p-cymene)]2 (5.0 mol%)KPF6 (20 mol%)Cu(OAc)2·H2O

Water, 120 °C, 20 hX = S, O, NMe X

HN−Me

O

CO2R

S

HN−Me

O

CO2Et

76%

O

HN−Me

O

CO2Et

64%(t-AmOH)

N

HN−Me

O

CO2Et

71%

Me

Scheme 2.13

functionalization of alkyl groups [2i, 95, 96]. This sp3C–H bond activation performedin water can inform on its role to improve activation and functionalization withrespect to organic solvents. Milstein [97] has reported a selective sp3C–H bond ac-tivation of 2-butanone by the cationic pincer iridium complex [(PNP)Ir(COE)][BF4](PNP, 2,6-bis(di-tert-butylphosphinomethyl)pyridine; COE, cyclooctene) in whichthe presence of water modifies the regioselectivity of sp3C–H bond oxidativeaddition (Equation 2.40).

In pure 2-butanone and 3-pentanone at 60 ◦C, sp3C–H bond activation atβ-position of the carbonyl preferentially takes place, and the resulting complexis stabilized by ketone chelation. By contrast, in the presence of water, both acetoneand 2-butanone lead to α-sp3C–H bond oxidative addition. In this case, the complexis stabilized by coordinated water, giving hydrogen bonding with the ketone oxygen,and formation of a six-membered cyclic intermediate [97].

N Ir

PtBu2

PtBu2

H

OR

BF4−

N Ir

PtBu2

PtBu2

BF4−

N Ir

PtBu2

PtBu2

O

R

HO

H

H

BF4−Acetone or

2-butanoneand water

60 °C, 3 h

2-butanone3-pentanone

60 °C, 3 hrt 3 days

R = Me, Et R = Me, Et

(2.40)

2.4.2Catalytic Enantioselective Alkynylation of sp3C–H Bonds

The direct formation of C–C bond via sp3C–H bond activation is one of the mostchallenging research topics for complex molecule synthesis, as it formally allowsthe functionalization of alkyl groups [98]. However, only a few examples of C–C


bond formation by catalytic activation of sp3C–H bond in water have been reported[9a], including CDC reactions [12].

In 2004, Li [98] first reported the enantioselectivity of coupling of N-benzenetetrahydroisoquinoline with phenylacetylene via sp3C–H bond activation, at carbonadjacent to nitrogen, which could be performed in water with oxidizing reagenttert-BuOOH. The reaction results from the in situ generation of imine intermediateon oxidation followed by nucleophilic addition of alkyne. However, modest enan-tiomeric excess was obtained in water (18%) by action CuOTf/L* catalytic systemas compared with that obtained in THF (63% ee) (Equation 2.41).

N + PHCuOTf (10 mol%)/L*

tBuOOH (1equiv)H2O, 50 °C, 2 days

N

Ph

*

18% ee

N

N

OO

N

L* (2.41)

The sp3C–H bond functionalization at carbon adjacent to nitrogen of alkylamineswas first discovered by Murahashi with RuCl3·nH2O with oxygen in MeOH/AcOHfor cyanation of N,N-dimethylaniline [99] and with copper salt and t-BuOOH foraddition of alkynes in decane by Li [100]. The latter mechanism of the reaction wasproposed to take place by oxidation/hydrogen abstraction, followed by nucleophilicaddition to the imine intermediate (Equation 2.42) [100].

R2

NR1

R3

[Cu]-OR

[Cu]R2

NR1 CH2R3

N

R2

R1

R3

R4

ROOH

R4Cu

ROH

−H2O+

+

(2.42)

2.4.3Cross-Dehydrogenative Coupling between sp3C–H Bonds Adjacent to a Heteroatom

Li [101] has also shown that indolyl tetrahydroisoquinoline derivatives could besynthesized via a CDC reaction between sp3C–H bonds and nucleophilic sp2C–Hbond of indole. It is catalyzed by 5 mol% CuBr in the presence of 1.3 equiv oft-BuOOH (TBHP : tert-butyl hydroperoxide) in mixed water/toluene (0.5 ml/0.1 ml).It corresponds to the nucleophilic addition of indole to the imine intermediate(Equation 2.43) [102]. But interestingly, when a large excess of water (water/toluene


(2 ml/1.0 ml)) was used, only the peroxide compound was obtained in 70% yield(Equation 2.44).

NPh

NH

NPh N

H

+

CuBr (5 mol%)TBHP (1.3 equiv)

H2O/PhMe (0.5 ml/0.1 ml)50 °C, overnight

50% (2.43)

NPh N

H

NPh

OOtBu

+CuBr (5 mol%)TBHP (1.3 equiv)

H2O/PhMe (2.0ml/1.0 ml)50 °C, overnight

70%

(2.44)It is noteworthy that the CDC reaction between isochroman and acetophenonecould proceed in water without metal catalyst, just in the presence of 1.2 equivDDQ (2,3-dichloro-5,6-dicyanobenzoquinone) (Equation 2.45) [103]. The reactioncorresponds to the addition of enolate to the oxonium species resulting fromoxidation of isochroman.

DDQ

O

O

N

N Cl

Cl

Me

O

ODDQ (1.2 equiv) O

O

+H2O, reflux

1 equiv 2 equiv 45%

(2.45)

The oxidative CDC between two different sp3C–H bonds of tertiary amines andnitroalkanes was reported by Li [104] using tert-BuOOH as the oxidizing reagentin organic solvent. In 2007, Li [105] performed this CDC alkylation between twodifferent sp3C–H bonds in water. The reaction in water was performed with tetrahy-droisoquinoline and nitromethane in the presence of 5 mol% CuBr for 16 h at 40or 60 ◦C (Equation 2.46). The reaction uses oxygen gas (1 atm) to replace peroxidesand constitutes a more atom-economical and safer process [106]. The reaction alsoproceeds in air and water without oxygen gas but requires longer reaction time.The N-p-methoxyphenyl substituted tertiary amine is more reactive than the simplephenyl substituted analog for this reaction, and it can take place at 40 ◦C [105]


N

R1NO2R2

R2 NO2

N

NO2

N

NO2

N

NO2 OMe

N

NO2 OMe

R1

N

R1 = H

R1 = OMe

+ CuBr (5 mol%)

O2 (1 atm), H2O40 °C or 60 °C, 16 h

R2 = H

R2 = Me

79% 75% 67% 69%(2.46)

In addition, the dialkyl malonate derivatives are also suitable for this oxidative CDCreaction and formal sp3C–sp3C cross-coupling took place with tetrahydroisoquino-line in the presence of copper salt under oxygen (Equation 2.47).

Ph

EWG EWG

NNPh

EWG

EWGH

EWG: CO2Me 63%CO2Et 59%

+CuBr (5 mol%)

O2 (1 atm),H2O60 °C, 2 h

(2.47)

The mechanism of this oxidative CDC reaction proceeds to first generateiminium-type intermediate via the copper-catalyzed oxidative of amines, followedby the Henry-type reaction [105]. Half of an oxygen molecule is used to generatethe imine-type intermediate (Scheme 2.14).

2.4.4Catalytic Enolate Carbon Coupling with (Arene) C–X Carbon

Domınguez has shown an advantageous route to oxcarbazepine (Trileptal) based onpalladium-catalyzed arylation. It is based on sp3C–H α-arylation of acetophenonesulfonamide and dibromobenzene catalyzed by palladium in PhMe/H2O mixtures[107]. This sp3C–H activation reaction actually corresponds to the cross-couplingof the ketone enolate with an sp2C-Br bond activated by the palladium catalyst.This reaction is performed in the presence of Pd(OAc)2/xantphos and Cs2CO3 inPhMe/H2O (v/v = 5.2) at 120 ◦C for 48 h. In comparison with the PhMe alone,the addition of water enhanced the selectivity so that the reaction proceeded morecleanly, but it took longer time than in PhMe alone (Equation 2.48). Xantphos


R2

NR1 CH2R3

R2

NR1

R3

[Cu]−OH

O−Cu(II)NR4

O

[Cu] Cu(II)

R4 NO2

NO2

R4N

R2

R1

R3

1/2 O2

+ H2O

Scheme 2.14

appears the best phosphorous ligand to lead to α-arylated product by additionof enolate to the oxidative addition aryl-PdBr intermediate, followed by reductiveelimination.

O

NH

Ts

Br

Br

O

NH

Ts

Br+

Pd(OAc)2 (3.7 mol%)Xantphos (5.4 mol%)

61%

Cs2CO3 (1.4 equiv)PhMe/H2O (v/v = 5.2),120 °C, 48 h

86%

Cs2CO3 (1.4 equiv)PhMe, 130 °C, 5 h

Pd(OAc)2 (4.4 mol%)Xantphos (8.5 mol%)

(2.48)

In 2006, Ma [108] reported the enantioselective arylation of 2-methylacetoacetatescatalyzed by CuI/trans-4-hydroxy-l-proline catalytic system at low reaction tempera-ture (−45◦C) in DMF/H2O mixtures via the Ullmann-type cross-coupling reaction(Equation 2.49). A variety of substituted ortho alkylated trifluoroacetanilides werethus obtained on reaction of 2-iodotrifluoroacetanilides with β-ketoesters. Theaddition of water led to a faster reaction [108, 109], and DMF/H2O mixtures weremore efficient than other solvents (DMSO, methylene chloride, dioxane, THF, andacetone) containing 0.5% water. An excellent yield of 70–82% and good enantiose-lectivities were obtained. For aryl iodides bearing an electron-withdrawing group,the reaction temperature needs to be increased to −20 ◦C.


O

O OR

Me

NHCOCF3

Me

O

O OBu-t

NHCOCF3

F

NHCOCF3

I

O

O OBu-t

Me

NHCOCF3

I

O

O OBu-t

Me

NHCOCF3

Y MeO

ROO

Y

Me

NHCOCF3O

O OEt

+ CuI/(2S, 4R )-4-hydroxyproline

NaOH/DMF/H2O−45 °C to −20 °C, 3−36 h

80% (71% ee) 77% (89% ee) 81% (83% ee) 79% (81% ee)

(2.49)

2.4.5Arylation of sp3C–H Bonds with Aryl Halides or sp2C–H Bond

Recently, Daugulis [110] has succeeded to perform arylation of nonactivated sp3C–Hbond of 2-methylthioanilide auxiliary in mixed water/alcohol solvent. This reactiontook place with 2-methylthioaniline auxiliary and iodobenzene in the presenceof 5 mol% Pd(OAc)2 and 2.5 equiv K2CO3 in t-Amyl-OH/H2O mixture at 90 ◦C(Equation 2.50). The mixed t-Amyl-OH/H2O solvent could lead to better selectivityfor the monoarylated product, without avoiding the formation of diarylated product.

ArI

SMe

NH

O H

R

Ar

SMe

NH

O Ar

R

NH

SMe

O

Br

Br

SMe

NH

O Ar

R

SMe

NH

O

Br

OCF3

SMe

NH

O

Me

+

Pd(OAc)2 (5 mol%)K2CO3 (2.5 equiv)

t -Amyl-OH/H2O (v/v = 4 : 1)90 °C, 12−26 h3-4 equiv

60%60%

+

9%

+

(2.50)

With one specific anilide, the isolation of a Pd(IV) cyclometalated intermediateinvolving the sp3C–H bond cleavage, at β-position of the carbonyl, provides evidencefor the formation of sp3C-Pd bond and arylation mechanism (Scheme 2.15).


Pd(OAc)2

N

NHCOtBu

N−Pd−OAc

NCOtBu

L-HOAc

N−Pd

NO

LI

MeMe Ar

N

HN

O

MeMe Ar

HI

AcOH

N−Pd

N

L

O

Me

Me

N−Pd

NO

Me

Me

L

I

Ar

ArI

+

+

Scheme 2.15

Recently, Zhang and coworkers [111] have reported a copper-catalyzed dehy-drogenative cross-coupling reaction between two molecules of N-para-tolylamideleading to the synthesis of 4H-3,1-benzoxazines in the presence of water. Thereaction involves the C–C coupling from an ortho arene C(sp2)-H bond and abenzylic methyl C(sp3)-H bond activation processes. This reaction was performedwith N-para-tolylamides in the presence of 10 mol% Cu(OTf)2, 10 mol% H2O, 2equiv of selectfluor as oxidant, and 1.0 equiv of HNTf2 in DCE at 120 ◦C for 1–3 h(Equation 2.51).

NHCOR1

R2

ON NHCOR1

R1

R2

R2

Cu(OTf)2 (10 mol%),H2O (10 mol%),Selectfluor (2.0 equiv),HNTf2 (1.0 equiv)

DCE, 120 °C, 1−3 h

54−91% yields (2.51)

A catalytic amount of H2O plays an important role for generating the copperhydroxo complex catalyst. The ESI/MS experiment showed that the Cu(III)(F)OHcomplex catalyst was generated in situ, which likely provided the intermolecularC–C bondcoupling intermediate first followed by intramolecular benzylic sp3C-Obond formation.

2.5Conclusion

The above-mentioned results demonstrate that a variety of C–H bonds can beactivated in water by metal catalysts and used for selective C–C bond formation

References 81

in water. The metal-catalyzed spC–H bond functionalization in water is now quitegeneral, either for nucleophilic addition of terminal alkynes to electrophiles or forthe Sonogashira-type reactions.

The catalyzed sp2C–H bond activation for C–C cross-coupling reactions via directarylation with aryl halides in pure water as solvent has emerged within the lastfive years especially with palladium and ruthenium(II) catalysts. It still constitutesa challenge as the catalyst activity can be improved and as for regioselectivitythe presence of a coordinating directing group is necessary. However, the directsynthesis of a variety of polyheterocyclic compounds can be efficiently reached byC–H bond heteroarylation in water, and it was demonstrated in some examplesthat water as solvent increases the catalyst activity.

The catalytic oxidative dehydrogenative cross-coupling reaction of two differentsp2C–H bonds is now possible in water with palladium catalysts in the presenceof a variety of oxidants such as benzoquinone or polyoxometalates with oxygenand usually with the cooperation of water-soluble ligand or surfactants. Thiscross-coupling reaction with ruthenium(II) catalysts associated with Cu(II) is quitenovel, as it started only in 2011 and already involves the alkenylation of arylcarboxylicacids or insertion of alkynes into both (aryl)C–H and N-H bonds of arylaniline andarylanilide derivatives. For these reactions, the environment of Ru(II) sites appearscrucial and likely the sp2C–H bond functionalization in water will attract the searchfor new active ruthenium(II) catalysts.

The sp3C–H bond activation at carbon adjacent of heteroatom in amines andethers is well documented, but only a few examples have been performed in water.They usually result from nucleophilic addition of enolate-type reagent to in situgenerated iminium or oxonium intermediates by oxidation or to sp2C–M speciesresulting from sp2C–Halide oxidative addition to palladium or copper catalyst. Thenonactivated functionalization of sp3C–H bonds remains a challenge and shouldlead soon to active development in this decade.

Acknowledgments

The authors are grateful to CNRS, the French Ministry for Research, the InstitutUniversitaire de France (P.H.D.), the ANR program 09-Blanc-0101-01, and theChinese Scholarship Council for a PhD grant to Bin Li.

References

1. Anastas, P.T. and Warner, J.C. (1998)Green Chemistry Theory and Practice,Oxford University Press, New York.

2. For reviews, see: (a) Choi, J.,MacArthur, A.H.R., Brookhart, M.,and Goldman, A.S. (2011) Chem.Rev., 111, 1761; (b) Lyons, T.W. andSanford, M.S. (2010) Chem. Rev., 110,

1147; (c) Colby, D.A., Bergmann, R.G.,and Ellman, J.A. (2010) Chem. Rev.,110, 624; (d) Satoh, T. and Miura, M.(2010) Synthesis, 3395; (e) Satoh, T. andMiura, M. (2010) Chem.—Eur. J., 16,11212; (f) Chen, X., Engle, K.M., Wang,D.-H., and Yu, J.-Q. (2009) Angew.Chem. Int. Ed., 48, 5094; (g) Seregin,


I.V. and Gevorgyan, V. (2007) Chem.Soc. Rev., 36, 1173; (h) Alberico, D.,Scott, M.E., and Lautens, M. (2007)Chem. Rev., 107, 174; (i) Campeau, L.C.and Fagnou, K. (2006) Chem. Com-mun., 1253; (j) Ritleng, V., Sirlin, C.,and Pfeffer, M. (2002) Chem. Rev., 102,1731.

3. For reviews see: (a) Kakiuchi, F. andMurai, S. (2002) Acc. Chem. Res., 35,826; (b) Kakiuchi, F. and Kochi, T.(2008) Synthesis, 3013; (c) Ackermann,L. (2010) Chem. Commun., 46, 4866; (d)Ackermann, L. (2011) Chem. Rev., 111,1315.

4. (a) Ozdemir, I., Demir, S., Cetinkaya,B., Gourlaouen, C., Maseras, F.,Bruneau, C., and Dixneuf, P.H.(2008) J. Am. Chem. Soc., 130, 1156;(b) Pozgan, F. and Dixneuf, P.H.(2009) Adv. Synth.Catal., 351, 1737.

5. For reviews, see: (a) Li, C.-J. (2010) inHandbook of Green Chemistry, Reactionsin Water, Vol. 5 (ed. P.T. Anastas andC.-J. Li), Wiley-VCH Verlag GmbH; (b)Butler, R.N. and Coyne, A.G. (2010)Chem. Rev., 110, 6302; (c) Chanda, A.and Fokin, V.V. (2009) Chem. Rev.,109, 725; (d) Shaughnessy, K.H. (2009)Chem. Rev., 109, 643; (e) Lindstrom,U.M. (2007) Organic Reactions in Water:Principles, Strategies and Applications,1st edn, Blackwell Publishing, Ox-ford; (f) Li, C.-J. (2005) Chem. Rev.,105, 3095; (g) Lindstrom, U.M. (2002)Chem. Rev., 102, 2751.

6. (a) Lastra-Barreira, B., Francos, J.,Crochet, P., and Cadierno, V. (2011)Green Chem., 13, 307; (b) Cadierno,V., Garcıa-Garrido, S.E., Gimeno, J.,Varela-alvarez, A., and Sordo, J.A.(2006) J. Am. Chem. Soc., 128, 1360;(c) Krasovskiy, A., Duplais, C., andLipshutz, B.H. (2009) J. Am. Chem.Soc., 131, 15592; (d) Nishikata, T. andLipshutz, B.H. (2009) J. Am. Chem.Soc.,131, 12103.

7. (a) Davies, D.L., Donald, S.M.A., andMacgregor, S.A. (2005) J. Am. Chem.Soc., 127, 13754; (b) Lafrance, M.and Fagnou, K. (2006) J. Am. Chem.Soc., 128, 16496; (c) Garcıa-Cuadrado,D., Braga, A.A.C., Maseras, F., andEchavarren, A.M. (2006) J. Am. Chem.

Soc., 128, 1066; (d) Lafrance, M.,Rowley, C.N., Woo, T.K., and Fagnou,K. (2006) J. Am. Chem. Soc., 128, 8754;(e) Garcıa-Cuadrado, D., Mendoza,P.D., Braga, A.A.C., Maseras, F., andEchavarren, A.M. (2007) J. Am. Chem.Soc., 129, 6880; (f) Lane, B.S., Brown,M.A., and Sames, D. (2008) J. Am.Chem. Soc., 130, 8050; (g) Racowski,J.M., Dick, A.R., and Sanford, M.S.(2009) J. Am. Chem. Soc., 131, 10974;(h) Li, L., Brennessel, W.W., and Jones,W.D. (2009) Organometallics, 28, 3492;(i) Davies, D.L., Macgregor, S.A., andPoblador-Bahamonde, A.I. (2010)Dalton Trans., 39, 10520.

8. (a) Narayan, S., Muldoon, J., Finn,M.G., Fokin, V.V., Kolb, H.C., andSharpless, K.B. (2005) Angew. Chem.Int. Ed., 44, 3275; (b) Klijn, J.E. andEngberts, J.B.F.N. (2005) Nature, 435,746.

9. (a) Herreias, C.I., Yao, X., Li, Z., andLi, C.-J. (2007) Chem. Rev., 107, 2546;(b) Li, C.-J. (2010) Acc.Chem. Res., 43,581; (c) Uhlig, N. and Li, C.-J. (2011)Chem. Sci., 2, 1241.

10. Lipshutz, B.H., Abela, A.R., Boskovic,Z.V., Nishikata, T., Duplais, C., andKrasovskiy, A. (2010) Top Catal., 53,985.

11. Fischmeister, C. and Doucet, H. (2011)Green Chem., 13, 741.

12. Li, C.-J. (2009) Acc. Chem. Res., 42,335.

13. (a) Li, C.-J. and Wei, C. (2002) Chem.Commun., 268; (b) Zhang, J.H., Wei,C., and Li, C.-J. (2002) TetrahedronLett., 43, 5731; (c) Wei, C. and Li, C.-J.(2003) J. Am. Chem. Soc., 125, 9584.

14. (a) Wei, C. and Li, C.-J. (2002) J. Am.Chem. Soc., 124, 5638; (b) Wei, C.,Mague, J.T., and Li, C.-J. (2004) Proc.Natl. Acad. Sci. U.S.A., 101, 5749.

15. Yao, X. and Li, C.-J. (2013) inMetal-catalyzed Reactions in Water,Chapter 3 (eds P.H. Dixneuf and V.Cadierno), Wiley-VCH Verlag GmbH,pp 87–108.

16. Chen, X., Xue, P., Sung, H.H.Y.,Williams, I.D., Peruzzini, M.,Bianchini, C., and Jia, G. (2005)Organometallics, 24, 87–108.

References 83

17. Coniglio, A., Bassetti, M.,Garcia-Garrido, S.E., and Gimeno,J. (2012) Adv. Synth. Catal., 354, 148.

18. Chen, L. and Li, C.-J. (2004) Tetrahe-dron Lett., 45, 2771.

19. Shaughnessy, K.H. (2013) inMetal-catalyzed Reactions in Water,Chapter 1 (eds P.H. Dixneuf and V.Cadierno), Wiley-VCH Verlag GmbH,pp 1–46.

20. Calsalnuovo, A.L. and Calabreze, J.C.(1990) J. Am. Chem. Soc., 112, 4324.

21. (a) Genet, J.P., Blart, E., and Savignac,M. (1992) Synlett, 715; (b) Genin, E.,Amengual, R., Michelet, V., Savignac,M., Jutand, A., Neuville, L., and Genet,J.-P. (2004) Adv. Synth. Catal., 346,1733.

22. Liang, B., Dai, M., Chen, J., and Yang,Z. (2005) J. Org. Chem., 70, 391.

23. (a) Davydov, D.V. and Beletskaya,I.P. (1995) Russ. Chem. Bull., 44, 965;(b) Bumagin, N.A., Bykov, V.V., andBeletskaya, I.P. (1995) Russ. J. Org.Chem., 31, 348.

24. (a) Bhattacharya, S. and Sengupta, S.(2004) Tetrahedron Lett., 45, 8733; (b)Wolf, C. and Lerebours, R. (2004) Org.Biomol. Chem., 2, 2161.

25. DeVasher, R.B., Moore, L.R., andShaughnessy, K.H. (2004) J. Org.Chem., 69, 7919.

26. Anderson, K.W. and Buchwald, S.L.(2005) Angew. Chem. Int. Ed., 44, 6173.

27. Li, C.-J., Chen, D.L., and Costello, C.W.(1997) Org. Res. Process Dev., 1, 325.

28. (a) Li, C.-J., Slaven, W.T., John, V.T.,and Banerjee, S. (1997) J. Chem. Soc.,Chem. Commun., 1569; (b) Li, C.-J.,Slaven, W.T. IV, Chen, Y.P., John,V.T., and Rachakonda, S.H. (1998)Chem. Commun., 1351.

29. Appukkuttan, P., Dehaen, W., andVan der Eycken, E. (2003) Eur. J. Org.Chem., 4713.

30. (a) Pal, M., Subramanian, V., andYeleswarapu, K.R. (2003) Tetrahe-dron Lett., 44, 8221; (b) Pal, M.,Subramanian, V., Batchu, V.K., andDager, I. (2004) Synlett, 1965; (c)Uozumi, Y., Kobayashi, Y., (2003)Heterocycles, 59–59.

31. Lamblin, M., Nassar-Hardy, L., Hierso,J.-C., Fouquet, E., and Felpin, J.-F.(2010) Adv. Synth. Catal., 352, 33.

32. Dawood, K.M., Solodenko, W., andKirschning, A. (2007) ARKIVOC, 5,104.

33. Gil-Molto, J., Karlstrom, S., and Najera,C. (2005) Tetrahedron, 61, 12168.

34. Cai, M., Xu, Q., and Sha, J. (2007) J.Mol. Catal. A, 272, 293.

35. Bergbreiter, D.E. and Liu, Y.-S. (1997)Tetrahedron Lett., 38, 7843.

36. Uozumi, Y. and Kobayshi, Y. (2003)Heterocycles, 59, 71.

37. Firouzabadi, H., Iranpoor, N., andGholinejad, M. (2010) J. Mol. Catal. A,321, 110.

38. Cai, C. and He, Y. (2011) J. Organomet.Chem., 696, 2689.

39. Saha, D., Dey, R., and Ranu, B.C.(2010) Eur. J. Org. Chem., 6067.

40. Khalafi-Nezhad, A. and Panahi, F.(2011) Green Chem., 13, 2408.

41. Cintas, P., Cravotto, G., Gaudino, E.C.,Orio, L., and Boffa, L. (2012) Catal. Sci.Tech., 2, 85.

42. Soberats, B., Martınez, L., Vega, M.,Rotger, C., and Costa, A. (2009) Adv.Synth. Catal., 351, 1727.

43. Cho, J.H., Prickett, C.D., andShaughnessy, K.H. (2010) Eur. J. Org.Chem., 3678.

44. (a) Pirguliyev, N.S., Brel, V.K., Zefirov,N.S., and Stang, P.J. (1999) Tetrahe-dron, 55, 12377; (b) Sheremetev, A.B.and Mantseva, E.V. (2001) TetrahedronLett., 42, 5759.

45. Beletskaya, I.P., Latyshev, G.V.,Tsvetkov, A.V., and Lukashev, N.V.(2003) Tetrahedron Lett., 44, 5011.

46. Chen, L. and Li, C.-J. (2004) Org. Lett.,6, 3151.

47. (a) Yanagisawa, S., Ueda, K.,Taniguchi, T., and Itami, K. (2008)Org. Lett., 10, 4673; (b) Liu, W., Cao,H., Zhang, H., Zhang, H., Chung,K.H., He, C., Wang, H., Kwong, F.Y.,and Lei, A. (2010) J. Am. Chem. Soc.,132, 16737; (c) Sun, C.-L., Li, H., Yu,D.-G., Yu, M., Zhou, X., Lu, X.-Y.,Kuang, K., Zheng, S.-F., Li, B.-J., andShi, Z.-J. (2010) Nat. Chem., 2, 1044;(d) Shirakawa, E., Itoh, K., Higashino,T., and Hayashi, T. (2010) J. Am. Chem.


Soc., 132, 15537; (e) Yanagisawa, S. andItami, K. (2011) ChemCatChem, 3, 827.

48. (a) Fujiwara, Y., Moritani, I., andMatsuda, M. (1968) Tetrahedron, 24,4819; (b) Fujiwara, Y., Moritani, I.,Danno, S., Asano, R., and Teranishi,S. (1969) J. Am. Chem. Soc., 1, 7166;(c) Jia, C., Kitamura, T., and Fujiwara,Y. (2001) Acc. Chem. Res., 34, 633; (d)Beccalli, E.M., Broggini, G., Martinelli,M., and Sottocornola, S. (2007) Chem.Rev., 107, 5318.

49. Ferrer-Flegeau, E., Bruneau, C.,Dixneuf, P.H., and Jutand, A. (2011)J. Am. Chem. Soc., 133, 10161.

50. (a) Kloek, S.M., Heinekey, D.M., andGoldberg, K.I. (2007) Angew. Chem.Int. Ed., 46, 4736; (b) Hanson, S.K.,Heinekey, D.M., and Goldberg, K.I.(2008) Organometallics, 27, 1454.

51. (a) Burton, H.A. and Kozhevnikov, I.V.(2002) J. Mol. Catal. A: Chem., 185,285; (b) Jintoku, T., Taniguchi, H., andFujiwara, Y. (1987) Chem. Lett., 1865.

52. Okamoto, M., Watanabe, M., andYamaji, T. (2002) J. Organomet. Chem.,664, 59.

53. Taj, S., Ahmed, M.F., andSankarapapavinasam, S. (1993) J.Chem. Res. Synop., 232.

54. (a) Sharma, V.B., Jain, S.L., andSain, B. (2003) Tetrahedron Lett., 44,2655; (b) Yadav, J.S., Reddy, B.V.S.,Gayathri, K.U., and Prasad, A.R.(2003) New J. Chem., 27, 1684; (c)Iwai, K., Yamauchi, T., Hashimoto,K., Mizugaki, T., Ebitani, K., andKaneda, K. (2003) Chem. Lett., 32, 58;(d) Doussot, J., Guy, A., and Ferroud,C. (2000) Tetrahedron Lett., 41, 2545.

55. Matsushita, M., Kamata, K.,Yamaguchi, K., and Mizuno, N. (2005)J. Am. Chem. Soc., 127, 6632.

56. Wallis, P.J., Booth, K.J., Patti, A.F., andScott, J.L. (2006) Green Chem., 8, 333.

57. Jiang, Y., Xi, C., and Yang, X. (2005)Synlett, 1381.

58. Xi, C., Jiang, Y., and Yang, X. (2005)Tetrahedron Lett., 46, 3909.

59. Lautens, M., Roy, A., Fukuoka, K.,Fagnou, K., and Martin-Matute, B.(2001) J. Am. Chem. Soc., 123, 5358.

60. Pivsa-Art, S., Satoh, T., Kawamura,Y., Miura, M., and Nomura, M. (1998)Bull. Chem. Soc. Jpn., 71, 467.

61. Park, C.-H., Ryabova, V., Seregin, I.V.,Sromek, A.W., and Gevorgyan, V.(2004) Org. Lett., 6, 1159.

62. Turner, G.L., Morris, J.A., andGreaney, M.F. (2007) Angew. Chem.Int. Ed., 46, 7996.

63. Ohnmacht, S.A., Mamone, P.,Culshaw, A.J., and Greaney, M.F.(2008) Chem. Commun., 1241.

64. Ferrer-Flegeau, E., Popkin, M.E., andGreaney, M.F. (2008) Org. Lett., 10,2717.

65. Hermann, W.A., Brossmer, C., Ofele,K., Reisinger, C.-P., Priermeier, T.,Beller, M., and Fischer, H. (1995)Angew. Chem. Int. Ed., 34, 1844.

66. Ohnmacht, S.A., Culshaw, A.J., andGreaney, M.F. (2010) Org. Lett., 12,224.

67. Nishikata, T., Abela, A.R., andLipshutz, B.H. (2010) Angew. Chem.Int. Ed., 49, 781.

68. (a) Shabashov, D. and Daugulis, O.(2007) J. Org. Chem., 72, 7720; (b)Daugulis, O. and Zaitsev, V.G. (2005)Angew. Chem. Int. Ed., 44, 4046; (c)Kalyani, D., Deprez, N.R., Desai, L.V.,and Sanford, M.S. (2005) J. Am. Chem.Soc., 127, 7330.

69. Joucla, L., Batail, N., and Djakovitch, L.(2010) Adv. Synth. Catal., 352, 2929.

70. Ackermann, L., Vicente, R., andAlthammer, A. (2008) Org.Lett., 10,2299.

71. Arockiam, P.B., Fischmeister, C.,Bruneau, C., and Dixneuf, P.H. (2010)Angew. Chem. Int. Ed., 49, 6629.

72. Arockiam, P., Poirier, V., Fischmeister,C., Bruneau, C., and Dixneuf, P.H.(2009) Green Chem., 11, 1871.

73. Ackermann, L. (2005) Org. Lett., 7,3123.

74. Ackermann, L., Hofmann, N., andVicente, R. (2011) Org. Lett., 13, 1875.

75. Lu, Z., Hu, C., Guo, J., Li, J., Cui, Y.,and Jia, Y. (2010) Org. Lett., 12, 480.

76. (a) Faccini, F., Motti, E., and Catellani,M. (2004) J. Am. Chem. Soc., 126, 78;(b) Catellani, M., Mealli, C., Motti,E., Paoli, P., Perez-Carreno, E., andPregosin, P.S. (2002) J. Am. Chem.

References 85

Soc., 124, 4336; (c) Campora, J.,Gutierrez-Puebla, E., Lopez, J.A.,Monge, A., Palma, P., Del Rıo, D.,and Carmona, E. (2001) Angew. Chem.Int. Ed., 40, 3641; (d) Thansandote,P., Gouliaras, C., Turcotte-Savard,M.-O., and Lautens, M. (2009) J. Org.Chem., 74, 1791; (e) Thansandote,P., Hulcoop, D.G., Langer, M., andLautens, M. (2009) J. Org. Chem., 74,1673; (f) Rudolph, A., Rackelmann, N.,Turcotte-Savard, M.-O., and Lautens,M. (2009) J. Org. Chem., 74, 289.

77. (a) Huang, Q., Fazio, A., Dai, G.,Campo, M.A., and Larock, R.C. (2004)J. Am. Chem. Soc., 126, 7460; (b) Wang,L., Pan, Y., Jiang, X., and Hu, H.(2000) Tetrahedron Lett., 41, 725; (c)Campora, J., Lopez, J.A., Palma, P.,Valerga, P., Spillner, E., and Carmona,E. (1999) Angew. Chem. Int. Ed., 38,147.

78. Boele, M.D.K., Van Strijdonok, G.P.F.,De Vries, A.H.M., Kamer, P.C.J.,De Vries, J.G., and Van Leeuwen,P.W.N.M. (2002) J. Am. Chem. Soc.,124, 1586.

79. Lee, G.T., Jiang, X., Prasad, K., Repic,O., and Blacklock, T.G. (2005) Adv.Synth. Catal., 347, 1921.

80. Yamada, T., Sakaguchi, S., and Ishii, Y.(2005) J. Org. Chem., 70, 5471.

81. Nishikata, T. and Lipshutz, B.H. (2010)Org. Lett., 12, 1972.

82. Lipshutz, B.H., GhOrai, S., Leong,W.W.Y., Taft, B.R., and Krogstad, D.V.(2011) J. Org. Chem., 76, 4379.

83. Li, Z. and Li, C.-J. (2006) J. Am. Chem.Soc., 128, 56.

84. Zhang, H.-B., Liu, L., Chen, Y.-J.,Wang, D., and Li, C.-J. (2006) Adv.Synth. Catal., 348, 229.

85. Zhang, H.-B., Liu, L., Chen, Y.-J.,Wang, D., and Li, C.-J. (2006) Eur. J.Org. Chem., 869.

86. (a) Yi, C.S. and Lee, D.W. (2009)Organometallics, 28, 4266; (b) Yi, C.S.and Lee, D.W. (2010) Organometallics,29, 1883; (c) Kwon, K.-H., Lee, D.W.,and Yi, C.S. (2010) Organometallics, 29,1883.

87. Ueyama, T., Mochida, S., Fukutani, T.,Hirano, K., Satoh, T., and Miura, M.(2011) Org. Lett., 13, 706.

88. Yamashita, M., Hirano, K., Satoh, T.,and Miura, M. (2010) Org. Lett., 12,592.

89. Ackermann, L. and Pospech, J. (2011)Org. Lett., 16, 4153.

90. Ackermann, L., Lygin, A.-V., andHofmann, N. (2011) Angew. Chem. Int.Ed., 50, 6379.

91. Li, B., Feng, H., Xu, S., and Wang, B.(2011) Chem.—Eur. J., 17, 12573.

92. Ackermann, L. and Fenner, S. (2011)Org. Lett., 13, 6548.

93. (a) Hashimoto, Y., Ueyama, T.,Fukutani, T., Hirano, K., Satoh, T.and Miura, M. (2011) Chem. Lett., 40,1165; (b) Padala, K. and Jeganmohan,M. (2011) Org. Lett., 13, 6144.

94. Ackermann, L., Wang, L., Wolfram, R.,and Lygin, A.V. (2012) Org. Lett., 14,728.

95. For representative reviews, see: (a)Dyker, G. (1999) Angew. Chem. Int.Ed., 38, 1698; (b) Shilov, A.E. andShul’pin, G.B. (1997) Chem. Rev., 97,2879; (c) Arndtsen, B.A., Bergman,R.G., Mobley, T.A., and Peterson, T.H.(1995) Acc. Chem. Res., 28, 154.

96. Guari, Y., Sabo-Etienne, S., andChaudret, B. (1999) Eur. J. Inorg.Chem., 1047.

97. Feller, M., Karton, A., Leitus, G.,Martin, J.M.L., and Milstein, D. (2006)J. Am. Chem. Soc., 128, 12400.

98. Li, Z. and Li, C.-J. (2004) Org. Lett., 6,4997.

99. Murahashi, S.-I., Komiya, N., Terai, H.,and Nakae, T. (2003) J. Am. Chem. Soc.,125, 15312.


101. Baran, P.S., Richter, J.M., and Lin,D.W. (2005) Angew.Chem. Int. Ed., 44,609.


103. Zhang, Y. and Li, C.-J. (2006) J. Am.Chem. Soc., 128, 4242.


105. Basle, O. and Li, C.-J. (2007) GreenChem., 9, 1047.

106. (a) Trost, B.M. (1991) Science, 254,1471; (b) Trost, B.M. (2002) Acc. Chem.Res., 35, 695.


107. Carril, M., SanMartin, R., Churruca, F.,Tellitu, I., and Domınguez, E. (2005)Org. Lett., 7, 4787.

108. Xie, X., Chen, Y., and Ma, D. (2006)J. Am. Chem. Soc., 128, 16050.

109. (a) Vogl, E.M., Groger, H., andShibasaki, M. (1999) Angew. Chem.Int. Ed., 38, 1570; (b) Dosa, P.I. and

Fu, G.C. (1998) J. Am. Chem. Soc., 120,445; (c) Taylor, M.S. and Jacobsen, E.N.(2003) J. Am. Chem. Soc., 125, 11204.

110. Shabashov, D. and Daugulis, O. (2010)J. Am. Chem. Soc., 132, 3965.

111. Xiong, T., Li, Y., Bi, X., Lv, Y., andZhang, Q. (2011) Angew. Chem. Int.Ed., 50, 7140.

Metal-Catalyzed Reactions in Water (Dixneuf/Metal-Catalyzed Reactions in Water) || Metal-Catalyzed...

Documents

Transcript of Metal-Catalyzed Reactions in Water (Dixneuf/Metal-Catalyzed Reactions in Water) || Metal-Catalyzed...