EROS Volume V and VIRuben MartinezBaran Group Meeting

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Lithium Hexamethyldisilazide (LHMDS )

Cl OMeLHMDS

THF, 0 °C86%

(TMS)2N OMe

formally a CH2NH2 unit

1) RMgX, Et2O

2) HO-H2N R

Synthesis of primary amines

Org. React. 1949, 5, 413.50-92%

Br LHMDS (2 equiv.)

Et2O, -20 ºC

N(TMS)2Liuseful precursor to unsaturated

protected primary aminesTetrahedron 1992, 48, 6231.

SiMe2SiMe2

+

SiMe2

SiMe2

CH2

SiMe2

SiMe3

Pd(PPh3)2 O

O

O

1 mol%

PhH, reflux, 36h13%

J. Organomet. Chem. 1977, 131 , 147.

Disilane metathesis(Maleic anhydride)bis(triphenylphosphine)palladium

O

SPh2

LiBF4

O

99% J. Am. Chem. Soc. 1973, 95, 7862.

rearrangement of oxaspiropentanes to cyclobutanonesLithium Tetrafluoroborate

N

∗∗

Li

1) 1 atm 11COTHF, -78 °C2) R3SnCl

N∗∗

O SnR3

R1I, Pd(PPh3)4

THF, refluxN∗∗

O R1

Lithium PyrrolidideIntroduction of 11C for biological and clinical studies.

J. Chem. Soc., Perkin Trans. 1 1988, 569.

NMeMeMe I

11

PrSLi

HMPA, 50 °CNMe

Me11

Me

Lithium 1-PropanethiolateDemethylation of quaternary ammonium salts.

J. Org. Chem. 1973, 38, 1961.99%

Lithium Perchlorate[1,3]-Sigmatropic rearrangement

O

HO

HO

Me

Me

H

H3.0M LiClO4

Et2OHO

HO

Me

Me

H

H

O

90%

J. Am. Chem. Soc. 1991, 113, 5488.

N

N

EtCO2MeMe N

MeSMe

O

NEt

1) LiDMSO

2) TsOH

J. Org. Chem. 1985, 50, 961.

Lithium MethylsulfinylmethylideA key player in the total synthesis of vindoline

Top 10 EROS Reagents in 2013

SiMe3

Me2Si CH2

e-EROS gives detailed information on more than 4,500 reagents and catalysts, and every year more than 200 new or updated articles are added in order to keep the Database up-to-date.

Editor-in-ChiefProfessor Philip L. FuchsPurdue University

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AcO

Me

O Me

HH

H

NAc

MeHO

HMe

H

AcO

I

O Me

HH

H

MeH

O

H

HgO, I2hν

cyclohexane, rt, 3d

Tetrahedron Lett. 1973, 4147.

AcO

Me

OH

H

Me R

H

H

HAcO

H

Me R

H

HO

HgO, I2hν

CCl4, reflux70%

50%

J. Am. Chem. Soc. 1964, 86, 1528.

Mercury(II) Oxide–IodineHydrogen Abstraction.

Mercury(II) Oxidetrans Diamination of alkenes

MeOH, HgO

HBF4, PhNH289%

NHPh

NHPhSynthesis 1981, 376.

BrHgO

Br280% Can. J. Chem. 1972, 50, 3109.

HO2C Br

CH2Br2HgO

Br280%

Bu3SnD, AIBN

93%

Synthesis 1976, 251.

Preparation of Alkyl Halides.

Ph

NNH2Ph

NNH2

HgO

PhH, refluxPhPh

Oxidation of hydrazones

Oxidations in Organic Chemistry; American Chemical Society: Washington, 1990.

MeMe

H2C

NMeMe

Me

H2C

Hg(NO3)2

MeCN

J. Org. Chem. 1982, 47, 4169.J. Chem. Soc., Chem. Commun. 1983, 384.

Mercury(II) Nitrate

I

I

I

I

F

F

F

IHgF2

70%J. Org. Chem. 1989, 54, 3796.

Mercury(II) FluorideMetathesis reactions

Mercuric Cyanide

Tetrahedron Lett. 2001, 42, 2077.

O

BrAcO

AcOOAc

N

HN NO2+

Hg(CN)2

MeNO2

81%

N

NO2N

OAcO

AcOOAc

N-Glycoside Formation.

Organometallics 1983, 2, 855.

Mercury (0)

Mercury selectively poisons heterogeneouscatalysts, particularly of the platinum group metals (PGM). This can be useful when ahomogeneous PGM catalyst decomposes with time to give the free metal; in such a case, Hg(0) can suppress the heterogeneouscomponent of the reaction. This can improve selectivity or givemechanistic information about which productsare attributable to which pathway.

Catalyst poison

AcO

Me

Me O

AcO

Me

Me SO

HSOH

BF3·OEt287%

J. Am. Chem. Soc. 1954, 76, 1945.

2-MercaptoethanolSteroidal ketone protection

D

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Methanesulfonyl ChlorideChlorination of allylic alcohols

OHR

R

MsCl, py

DMF, collidine83%

ClR

RJ. Org. Chem. 1971, 56, 3044.

Mild elimination of iodohydrins

O OI

HOOBn

MsCl, py

quench with Na2S2O3>99%

O O

OBn

Tetrahedron Lett. 1972, 107.

PhCONEt2 Ph

CONEt2OH

OH

AD-mix-βMeSO2NH2

t-BuOH, H2O, 0 °C96%

96% ee

Catalyst turnoverMethanesulfonamide

J. Org. Chem. 1992, 57, 2768Tetrahedron Lett. 1993, 34, 2079.

Me

Me

S MeOO

OH2N

O-(Mesitylsulfonyl)hydroxylamine

NPhBr

NN Ph

57%

OMSH

NaOHOMSH

Synthesis 1973, 159.J. Chem. Soc., Perkin Trans. 1 1977, 924.

NH2 transfer to nucleophiles

t-Bu

t-Bu t-Bu

H

Se

Me

Me

Me

B B

Me

Me

Me

TMSTMSLi

Angew. Chem., Int. Ed. Engl. 1988, 27, 961. Chem. Commun. 1986, 71.

Low-coordinate main group element derivativesMesityllithium

Allylic diazene rearrangementMesitylenesulfonylhydrazide

O

O

H

H

HO NCO2Me

OMeH

Me H

O

O

H

H

NCO2Me

OMeH

Me H1) MeAlCl2 -78 °C to -35 °C2) MSH, -78 °C to 0 °C

92%

J. Am. Chem. Soc. 1992, 114, 5898.

Mercury(II) Trifluoroacetate

HO HOO

MeMeHg(CF3CO2)2

Tetrahedron Lett. 1975, 2605.

HR H

OH

1) Hg(CF3CO2)2DCM, NaCl

2) LAH, THF

MeR

OH

OH

Acc. Chem. Res. 2003, 36, 766.

Cyclopropane Ring Openings

Oxymercuration

AcOOH

H H

Me

AcOO

H

β-fragmentation

HgO,I2hν

CCl4, 2 h, rt

J. Chem. Soc. (C) 1966, 937.Tetrahedron 1977, 33, 441.

Mercury(II) Oxide–Iodine cont.

Me

H

(E), 63%; (Z), 10%

EROS Volume V and VIRuben MartinezBaran Group Meeting

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Molybdenum (VI) Fluorideoxygen to fluorine exchange

R R1

O MoF6BF3·OEt2

DCM, 20 ºC R R1

FF+ MoOF4

CF3 group installation

Br CF3Br CO2HMoF6

160 °C, 64 h89%

N CO2HHO2C

MoF6

200 °C, 45 h84%

N CF3F3Creactions must be run in a stainless steel autoclave

Tetrahedron 1971, 27, 3965.Tetrahedron 1975, 31, 391.

J. Fluorine Chem. 1979, 13 , 375.

J. Gen. Chem. USSR (Engl. Transl.) 1983, 53, 85.

Methyl Fluoride-Antimony (V) FluorideMeF/SbF5 is the most reactive methylating agent reported.

FF

FF F

F

FF

SO2ClF40-50%

MeF/SbF5

FF

FF F

F

FMe F

F

FF F

F

MeF

+

SO O

MeF/SbF5

SO2 SO OMe

CF3IMeF/SbF5

SO2CF3IMe

Can. J. Chem. 1984, 62, 69. Z. Naturforsch., Teil B 1991, 46b, 884.

Ot-Bu

Me t-Bu t-Bu Me

t-BuO

AlMe

Methylaluminum Bis(2,6-di-t-butyl-4-methyl)

MAD

Ph OMe+ Ph OEt

MAD

J. Am. Chem. Soc. 1990, 112 , 6115.

Ph OMe

AlR3

+Ph OEt

MeBBN

2) HOAc, -30 °C3) H2O2, NaOH

Li

OMe1)

THF, -30 °C

Me

OMe

1-Methoxyallenyllithium

Tetrahedron Lett. 1980, 21, 537.

OH

CH2

OMe O

OMe

O

O

6N HClt-BuOK

crown ether

t-BuOH, 4h, reflux74%

J. Am. Chem. Soc. 1978, 100 , 7746.

O

O

O

O

O

O

J. Am. Chem. Soc. 1980, 102 , 2134.

Helixanes: The first primary helical molecules: polyoxapolyspiroalkanones

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Chem. Lett. 1991, 641.

O

Ni(dpm)2 1 mol%i-PrCHO, O2

O

O

91% epoxidation of olefins also possible with same conditions

Ni(dpm)2Catalyst for oxidations

O

Me Me

H

N

O

Me Me

H

O

ONHAc

AcHN

O

NHOHNBu4IO4

0 ºC

Heterocycles 1989, 28, 147.

Nitrosocarbonylmethane

ClNO

NOH

hνH2SO4 NH

O

caprolactam4.5 billion kg produced annually.

HN

O

5n

533 °K

N2

Nylon 6

Nitrosyl ChlorideThe most important reagent in this GM

Fortschr. Chem. Forsch. 1967, 7, 559.

O2N

O2NO2N

O2N

HNO2

NO2

NO2

O2N

O2NO2N

O2N

NO2NO2

NO2

NO2

1) LiN(TMS)22) ClNO

3) O3

Angew. Chem., Int. Ed. 2000, 39, 401.

Needs more nitro!!!

OsO4–t-BuOOHoxidation TMS alkynes to α-keto esters

R TMSOsO4, TBHP

MeOH R

O

CO2Me60%

Tetrahedron Lett. 1986, 27, 1947.Oxalic AcidDecarboxylation of β-ketoesters

Chem. Soc., Chem. Commun. 1990, 1047.

NCO2Et

Me

OEtO2C

NCO2Et

Me

O(CO2H)2

H2O, dioxane81%

R

OF3C

OPd

OO t-Bu

PPT

PPT

Palladium tert-Butyl Peroxide Trifluoroacetateselective oxidation of terminal alkenes to methyl ketones

RO

internal alkenes form stableη3-allyl Pd complexesJ. Am. Chem. Soc. 1980, 102, 1047.

Phenyliodine(III) Bis(trifluoroacetate)Bond cleavage.

PIFACCl4, 20°C

OCOCF3

OCOCF3

(PIFA)

R

OR1 R

OR1

OH

PIFA, TFA

MeCN-H2O

J. Org. Chem. USSR (Engl. Transl.) 1981, 17, 1685.

EROS Volume V and VIRuben MartinezBaran Group Meeting

01/24/15

peptide

O

R

NH2 PhNCSpeptide

O

R

HN

HN

SPh

N NH

S

Ph

O R

HCl

MeNO2

OH-HO2C

R

NH2

Edman degradation of peptidesPhenyl Isothiocyanate

Acta Chem. Scand. 1950, 283.Fieser & Fieser 1967, 1, 844.Fieser & Fieser 1969, 2, 323.

The procedure, which is amenable to complexpeptides containing a variety of sensitive functionalities, has been applied tothe vancomycin group of antibiotics.

PhP

Cl

Se

Cl

Phenyl(seleno)phosphonic Dichloride

J. Chem. Soc., Chem. Commun. 1988, 1494.

NMe

O NMe

Se in xylene95 °C 96%

Oxygen–Selenium Exchange

PhenylthiomethyllithiumEpoxide Synthesis The overall yields for the three-step process are high and

compare favorably to the one-step methylene transfer accomplished by sulfur ylides, a reaction that is sometimeshindered by steric interference and proton abstraction.

Ph

O

Ph PhPhOPhSCH2Li 1) Me3OBF4

2) aq NaOHPhPh

HO SPh

88% 90%

Me

CHOPhSCH2Li

Me

OHSPh

1) Et3OBF4

2) NaH

Me

O

J. Am. Chem. Soc. 1973, 95, 3429.

Pure Appl. Chem. 1987, 59, 385.

P

N-t-Bu

N N

N

P P

PMe2N NMe2

NMe2

NMe2

NMe2

NMe2

NMe2

Me2NNMe2

Phosphazene Base P4-t-Bu

Alkylations of Carbanions

Angew. Chem., Int. Ed. Engl. 1987, 26, 1167.

Schwesinger's base

O O

t-Bu

MeMe

O

i-PrIP4-t-Bu

O O

t-Bu

Me Oi-Pr Me

45%

use of LDA or KHMDS gave only decomposition

OO

Me

P4-t-BuEtI O

O

Me EtEt68%

Schwesinger, R.; Hasenfratz, C. Unpublished results.

Chem. Ber. 1990, 124, 1837.

N

Ph O

BrBr1) PBr32) Br2

72%

Phosphorus(III) Bromide

Org. Synth., Coll. Vol. 1941, 1, 428.

Alkene Preparation.

OHHO

1) PBr3, CuBr2) Zn

J. Am. Chem. Soc. 1975, 97, 3252.

Org. Synth. 1989, 67, 210.

OEt

OTMS

PBr3

72%

66%

OEt

Br

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R

OC6H13

1) O3, DCM, -78 °C2) PI3

87%

R

OH

J. Chem. Soc., Perkin Trans. 1 1981, 1744.

An advantage over the traditional PPh3 reduction is the formation of water-soluble phosphorusbyproducts from PI3.

Phosphorus(III) Iodidereduction of ozonides

MeO

O

OO

Me

H H

MeMe

OO

O

Me

H H

Me

SEt

PPA, EtSH90 °C

Polyphosphoric AcidSelective epoxide opening

Chem. Pharm. Bull. 1967, 15, 887.

OH

OH

1) n-BuLi, THF2) K2WCl6, 65 °C

66% cis:trans = 73:27

Potassium Hexachlorotungstate(IV)

J. Chem. Soc., Chem. Commun. 1972, 370.

One pot conversion of 1,2-diols to alkenes

Potassium Monoperoxysulfate (Oxone)

Modification of Oxone: Since Oxone is a triple salt(2KHSO5·KHSO 4·K2SO4) only about 50% per mole is activeoxidant. A convenient method for the preparation of purifiedKHSO5·H2O on a large scale has been developed which allowsfor significant reduction in the amount of oxidizing agent neededfor a reaction.

H

O1 equiv Oxone

MeOH OMe

O

Tetrahedron 1998, 54, 401.83%

H

O1 equiv Oxone

DMF OH

O

97% Org. Lett. 2003, 5, 1031.

OH O

O4 equiv Oxone0.01 equiv OsO4

DMF, rt73%

Org. Lett. 2003, 5, 3089.

direct synthesis of lactones from alkenols

Potassium Monoperoxysulfate (Oxone)

Pyridinium Chlorochromate

OH

Me

2.5 equiv PCC

DCM, rt, 36 h

O

Me

Me

O

Me

Me

Me

70%

NaOH

EtOH

oxidative cationic cyclizationPCC

Tetrahedron Lett. 1978, 2461.

2-Pyrrolidone HydrotribromideSelective Bromination

OO

Br

PHTTHF N

O

O

N

O

O

BrPHTpyrrolidone

THF, reflux82%

O

O

PHTTHF96%

O

O

Can. J. Chem. 1969, 47, 706. Synthesis 1990, 59.

Bull. Chem. Soc. Jpn. 1986, 59, 3311.Eur. J. Org. Chem. 2002, 3429.

2KHSO5·KHSO4·K2SO4

EROS Volume V and VIRuben MartinezBaran Group Meeting

01/24/15

Rhodium(III) Chlorideselective reagent for the reduction of aromatic systems

HO2CNHCOMe

NaBH4, 2 equiv RhCl3

EtOH, 2 h, rt94%

Tetrahedron Lett. 1982, 23, 193.

HO2CNHCOMe

Ruthenium(III) ChlorideC–H Activation

O OO

EtRuCl3·3H2O

EtOH, 140 °CJ. Chem. Soc., Chem. Commun. 1986, 1255.75%

OHO

HO

ORuCl3, aq. CH3CO3H

MeCN, DCM, H2O, 0 to 20 °C58%

Tetrahedron Lett. 1998, 39, 7691.

Oxidation

Hydrogen Borrowing

CN MeO

OH

9.5 equiv

+ N

OMe

MeO

OMe

5 mol% RuCl3·H2O10 mol% dppf

PhMe, 150 °C 16 h84%

Chem. Lett. 2011, 40, 489.

Samarium(II) Iodide

O

MeMei-Pr

SePh O

O PMP

O

OPMP

Me

O

i-Pr

Me SmI2-HMPATHF, rt, 15 minthen PhSeBr

Reductive C-C cleavage of cyclobutane en route to (+)-guanacastepene A

50%J. Am. Chem. Soc., 2006, 128 , 7025.

NO

SEMN

Br Br

OTBS

CO2MeNHNHN

O

S

NO

SEMN

Br Br

OTBS

CO2MeNH2

NHHN

O

S

SmI2-MeOHTHF, rt, 15 min

79 %

J. Am. Chem. Soc., 2007, 129 , 12896.

N-N bond cleavage in a complex setting

Chem. Soc. Rev. 2013, 42, 9155.