Journal Years in Review: Organic Letters 1999 · 2017. 3. 24. · (vi) T. Nikaoido Org. Lett. 1999,...

Gaich-Group Seminar !

Erik Stempel 31.07.2014

Journal Years in Review: Organic Letters 1999

Gaich-Group Seminar Erik Stempel In

tro

2

Introduction / Analysis■ OL facts 1999 (2013 in parentheses):

■ Impact Factor: 3.367 (6.142, +82%)■ 2 184 pages (6 308, +189%)■ 561 published articles (1 738, +210%)■ 29 “Total Syntheses” as topic (93, +221%)

■ Most prolific authors of 1999:

■ E. J. Corey (8)A. B. Smith (8)

■ D. L. Comins, (4)Y. Fujiwara, (4)K. N. Houk, (4)M. E. Jung, (4)T. Kitamura, (4)A. Jain, (4)T. Nakata, (4)J. D. Rainier, (4)W. R. Roush, (4)J. F. Stoddart, (4)P.A. Wender (4)

Published Articles — Country

United StatesJapan

GermanyCanada

United KingdomSpain

FranceIndiaItalia

China0 100 200 300 400 500

435

25

106

92

58

88

52

104

217

386

7

10

11

14

22

23

24

28

68

310

19992013 (+/– %)

■ Scopus / SciFinder

Section “Total Synthesis” — Country

United States

Japan

United Kingdom

Canada

Germany

China

Australia

India

South Korea

Hong Kong

0 5 10 15 20

3

3

6

6

18

5

5

8

15

19

0

0

0

0

0

1

1

2

7

19

19992013

(+25%)

(+219%)

(+271%)

(+117%)

(+283%)

(+164%)

(+557%)

(+864%)

(+150%)

(+6114%)

Gaich-Group Seminar Erik Stempel

■ Scopus / SciFinder

Intr

o

3

Introduction / Analysis (II)■ Most cited papers (general):

■ Synthesis and activity of a new generation of ruthenium-based olefin metathesis catalysts coordinated with 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligands (R. H. Grubbs, p. 953)■ Number of citations: 2497

■ The Heck Reaction in Ionic Liquids: A Multiphasic Catalyst System (J. D. Holbrey, p. 997)■ Number of citations: 423

■ Enantioselective Synthesis of α-Amino Nitriles from N-Benzhydryl Imines and HCN with a Chiral Bicyclic Guanidine as Catalyst (E. J. Corey, p. 157)■ Number of citations: 370

!■ Most cited papers (section „Total Synthesis“):

■ Total Synthesis of (+)-Laurencin (M. T. Crimmins, p. 2029)■ Number of citations: 93

■ Asymmetric Total Synthesis of (+)-Dictamnol (P. A. Wender, p. 137)■ Number of citations: 87

■ An Enantioselective Total Synthesis of (+)-Geissoschizine (S. F. Martin, p. 79)■ Number of citations: 64

http://pubs.acs.org/doi/abs/10.1021/ol990909q

http://pubs.acs.org/doi/abs/10.1021/ol9907771

http://pubs.acs.org/doi/abs/10.1021/ol990623l

http://pubs.acs.org/doi/abs/10.1021/ol991201e

http://pubs.acs.org/doi/abs/10.1021/ol990599b

http://pubs.acs.org/doi/abs/10.1021/ol990554a


Nat

. Pro

d.

■ (i) S. Kadota Org. Lett. 1999, 1, 1367–1370. (ii) A. D. Rodríguez Org. Lett. 1999, 1, 337–340. (iii) Y. Kashman Org. Lett. 1999, 1, 471–472. (iv) K. Y. Sim Org. Lett. 1999, 1, 879–882. (v) J. Schripsema Org. Lett. 1999, 1, 1169–1171. (vi) T. Nikaoido Org. Lett. 1999, 1, 197–198. (vii) S. Kadota Org. Lett. 1999, 1, 1733–1736.

Isolated Natural Products

4

OBzO

AcO

AcOH

OHH

BzO

O

O

staminolactone A (1)

O

O

OHO

O

HO

HOO

OHO

H

bisgersolanolide (6)

H

CO2H

bilosespen A (2)(synthesis: Org. Lett. 2003, 5, 4741–4743)

OH

O O O

O

sampsonione I (5)

OH

O

HHO OH

HO

borreriagenin (3)

O

OH

OHHO

HO O

S

OH

O

O

OH

echinothiophene (4)

O

HO OH

HO OH

MeO O

OH

epicalyxin F (7)

OH

MeO O

OHO

HO

OH

HO

epicalyxin F (8)(revised structure and synthesis: Org. Lett. 2007, 9, 4955–4958.)


Tota

l Syn

.

Selected Detailed Syntheses

5


Tota

l Syn

.

■ P. A. Wender Org. Lett. 1999, 1, 137–139.

(+)-Dictamnol — Wender

6

9 10 11

12

H

O

NaH, THF, rt., 2 hO

NOMe(EtO)2P

O

N

OOMe

I •1. 1. tBuLi, Et2O,1. –78 °C to rt.2. CBS reduction

HO

•

90% 64%, 93% ee

[Rh(CO)2Cl]2 (2.5 mol-%),DCE, 80 °C, 0.025 M, 7 h

H

HORhLn

H

HH

H

H

HO

76%

DMP, DCM

80%H

H

O

MeMgBr, Et2O, 0 °C

50%(1:1 mixture of epimers)H

H

HO

1314(+)-dictamnol (15)

■ Key features:■ concise synthesis, 6 steps, 18% overall yield (9% pure epimer)■ fast access to cycloaddition precursor■ [5+2] cycloaddition■ asymmetric center is used to control relative stereochemistry

during CA process

O

OHHO

OH

OH OH

HHH

phorbol (16)


Tota

l Syn

.

■ D. L. Comins Org. Lett. 1999, 1, 229–231.

(+)-Luciduline — Comins

7

■ Key features:■ concise synthesis, 14 steps, 10% overall yield■ IMDA–retro-Mannich sequence for the synthesis of cis-decahydroquinoline skeleton

18

17

80%(R* = (+)-TCC)

NCO2R*

Cl

OMeTIPS

MgCl

then H+ / H2O

,

NCO2R*

OTIPS

1. NaOMe, MeOH,1. then 10% HCl2. nBuLi, BnOCOCl

NCO2Bn

OTIPS

88%

1. OsO4 (cat.), NaIO42. (MeO)2P(O)CH2CO2Me,2. KOtBu, THF

NCO2Bn

OTIPS

CO2Me

98%

75%

NCO2Bn

TIPS

CO2Me

1. NaBH4 , CeCl32. MsCl, DMAP,2. DCM, H2O

HN

CO2Me 1. xylenes, 140 °C, 21 h2. H2 , Pd/C

85%

LDA, iPr2NH,then TMSCl

N

OTMS

OMeH

HTMS

(H, TMS)BnOCOCl, DCM, ∆,then H+ / H2O

N

CO2MeH

HCO2Bn

51%(2 steps)

1. DIBAL2. SnCl4 , Et3SiH,2. PhMe, –20 °C

46%

N

H

HCO2Bn

OH

N

HO

CO2Bn

DMPN

O

CO2Bn

Pd/C, MeOH,H2 , formalin

N

O

OHPh

(+)-TCC = (+)-trans-2-(α-cumyl)(+)-TCC = cyclohexanol

Me

99% 95%

19 20

21

22

80%(R* = (+)-TCC)

NCO2R*

Cl

OMeTIPS

MgCl

then H+ / H2O

,

NCO2R*

OTIPS


NCO2Bn

OTIPS

88%


NCO2Bn

OTIPS

CO2Me

98%

75%

NCO2Bn

TIPS

CO2Me


HN


85%


N

OTMS

OMeH

HTMS


N

CO2MeH

HCO2Bn

51%(2 steps)


46%

N

H

HCO2Bn

OH

N

HO

CO2Bn

DMPN

O

CO2Bn


N

O

OHPh


Me

99% 95%

232425

80%(R* = (+)-TCC)

NCO2R*

Cl

OMeTIPS

MgCl

then H+ / H2O

,

NCO2R*

OTIPS


NCO2Bn

OTIPS

88%


NCO2Bn

OTIPS

CO2Me

98%

75%

NCO2Bn

TIPS

CO2Me


HN


85%


N

OTMS

OMeH

HTMS


N

CO2MeH

HCO2Bn

51%(2 steps)


46%

N

H

HCO2Bn

OH

N

HO

CO2Bn

DMPN

O

CO2Bn


N

O

OHPh


Me

99% 95%

26 26 27 (+)-luciduline (28)

80%(R* = (+)-TCC)

NCO2R*

Cl

OMeTIPS

MgCl

then H+ / H2O

,

NCO2R*

OTIPS


NCO2Bn

OTIPS

88%


NCO2Bn

OTIPS

CO2Me

98%

75%

NCO2Bn

TIPS

CO2Me


HN


85%


N

OTMS

OMeH

HTMS


N

CO2MeH

HCO2Bn

51%(2 steps)


46%

N

H

HCO2Bn

OH

N

HO

CO2Bn

DMPN

O

CO2Bn


N

O

OHPh


Me

99% 95%

OHPh


IMDAretro-Mannich


94%O H

I OTBS3

NaCH2S(O)CH3

OOTBS 84%

Ph2O, 250 °COTBS

O

O

1. MeLi, Et2O2. PCC, MS 4 Å3. TBAF, THF4. PCC, MS 4 Å5. NaH, (MeO)2P(O)CH2CO2Me

75%

CO2Me

LiHMDS,–78 °C to 0 °C

CO2Me

O

1. KOH2. HOTT, NEt3 , DMAP,2. 1,4-dioxane, tBuSH,2. O2 , P(OMe)3

OH

O

OHOH

Li, NH3 ,MeOH, –78 °C

94%81%>99%

DoubleMichael Addition

Tota

l Syn

.

■ K. Takasu Org. Lett. 1999, 1, 391–393.

(±)-Culmorin — Takasu

8

■ Key features:■ 11 steps, 45% overall yield■ construction of the culmorin framework via double Michael addition

R OH

ONO

S NMe2

NMe2

PF6

HOTT

Me2N NMe2

OR O

ON

S

Barton ester formation

R O

Oradicalinitiation

R–CO2

radicaltrap substitution or

addition products

HOTT

29 3031

323334(±)-culmorin (35)


Tota

l Syn

.

■ H. Nemoto Org. Lett. 1999, 1, 517–519.

(±)-Scirpene — Nemoto

9

■ Features:■ quite long (maybe overcomplicated?) synthesis, 25 steps, 4% overall yield■ take-home message: ring-expansions, decarbonylation using Wilkinson’s catalyst

77%

OMe

O

BrPh3P1. NaH,2. mCPBA, NaHCO3

OMeO 1. NaBH4

2. TBSCl, imid.

>99%

OMeOTBS Na, NH3 (aq.),

then (CO2H)2 , MeOH

50% of XX ,8% of XX

XOTBS

CrO3 ⋅ 3,5-DMP,4 Å MS (60%)

9:1 d.s.1. NaBH4 , CeCl3 ⋅ 7H2O2. ethyl vinyl ether, Hg(TFA)2 ,2. then Et3N–PhMe (1:4), 200 °C

OTBS

O

1:1 d.s.

1. NaBH42. MOMCl, DIPEA3. CrO3 ⋅ 3,5-DMP, 4 Å MS4. MeLi, Et2O

74%

OTBS

MOMO

HO1.2:1 d.s.

82%

O

OH

1. dilute HCl2. Swern [O]3. vinyl-MgBr, CeCl3

82%62%

PdCl2(MeCN)2 (1.0 eq.),p-quinone, DMAO

O

1. DIBAL2. TBSOTf, 2,6-lutidine3. AcOH–H2O–THF (3:1:1)

82%

HO

OTBS1. PivCl, pyr., DMAP2. CSA

PivO

OH H

1. DIBAL2. Swern [O]3. Rh(PPh3)3Cl,3. PhMe, ∆

OH H

OH H

mCPBA O

ring expansion

Pd mediated ring expansion

decarbonylation

ether formation

>99% 65%

36 37 38 39: X = O

40: X= H₂

3940

414243

77%

OMe

O


OMeO 1. NaBH4

2. TBSCl, imid.

>99%


then (CO2H)2 , MeOH

50% of XX ,8% of XX

XOTBS

CrO3 ⋅ 3,5-DMP,4 Å MS (60%)


OTBS

O

1:1 d.s.


74%

OTBS

MOMO

HO1.2:1 d.s.

82%

O

OH


82%62%


O


82%

HO


PivO

OH H


OH H

OH H

mCPBA O

ring expansion


decarbonylation

ether formation

>99% 65%

77%

OMe

O


OMeO 1. NaBH4

2. TBSCl, imid.

>99%


then (CO2H)2 , MeOH

50% of XX ,8% of XX

XOTBS

CrO3 ⋅ 3,5-DMP,4 Å MS (60%)


OTBS

O

1:1 d.s.


74%

OTBS

MOMO

HO1.2:1 d.s.

82%

O

OH


82%62%


O


82%

HO


PivO

OH H


OH H

OH H

mCPBA O

ring expansion


decarbonylation

ether formation

>99% 65%

44

77%

OMe

O


OMeO 1. NaBH4

2. TBSCl, imid.

>99%


then (CO2H)2 , MeOH

50% of XX ,8% of XX

XOTBS

CrO3 ⋅ 3,5-DMP,4 Å MS (60%)


OTBS

O

1:1 d.s.


74%

OTBS

MOMO

HO1.2:1 d.s.

82%

O

OH


82%62%


O


82%

HO


PivO

OH H


OH H

OH H

mCPBA O

ring expansion


decarbonylation

ether formation

>99% 65%

45 46 47(±)-scirpene (48)

77%

OMe

O


OMeO 1. NaBH4

2. TBSCl, imid.

>99%


then (CO2H)2 , MeOH

50% of XX ,8% of XX

XOTBS

CrO3 ⋅ 3,5-DMP,4 Å MS (60%)


OTBS

O

1:1 d.s.


74%

OTBS

MOMO

HO1.2:1 d.s.

82%

O

OH


82%62%


O


82%

HO


PivO

OH H


OH H

OH H

mCPBA O

ring expansion


decarbonylation

ether formation

>99% 65%


Excu

rsus

Excursus: Decarbonylation with Rh(PPh₃)₃Cl■ Rh(PPh₃)₃Cl reacts with CO to give trans-RhCl(CO)(PPh₃)₂.

This complex is structurally analogous to Vaska's complex,but much less reactive.

■ The same complex arises from the decarbonylationof aldehydes.

■ The process is non-catalytic → stoichiometric amounts of the complex is required

■ Catalytic cycle possible by addition of stoichiometric amounts of DPPA.

10

Cl Ir COPPh3

Ph3P

Vaska’s complex

Rh PPh3Ph3PCl (I)

RhPPh3

Ph3P

Cl (I)

PPh3

RhPh3P

Cl (III)

R

O

PPh3

H

RhR

Ph3P

Cl

CO

H

PPh3

RhPPh3

Ph3P

Cl

COR H

R

O

H

oxidativeaddtion

– PPh3

deinsertion

reductiveelimination

Dissociaition of CO ligand is notpossible under normal conditions

dark red bright yellow

RhCO

Cl

Ph3P

PPh3

DPPARh

N

Cl

Ph3P

PPh3CO

N NPO

OPh

RhN2

Cl

Ph3P

PPh3

OPh

PhO PO

NCOPhO

– N2 Rh PPh3ClPh3P


Tota

l Syn

.

■ T. Fukuyama Org. Lett. 1999, 1, 973–976.

(±)-Catharanthine — Fukuyama

11

■ Key features:■ convergent synthesis, 17 steps (longest linear sequence), 8% overall yield■ take-home message: formation of 1,2-dihydropyridine, Reissert reaction, indole synth.

49 50 51

N1. BnBr, 0 °C to rt.2. NaBH4 , EtOH, 0 °C to rt.3. CbzCl, PhH, ∆

62%

NCbz

1. Br2 , DCM, rt. (97%)2. DABCO, MeCN, ∆

NCbz

CO2EtEtO2C

OEt

1. H2 , Pd/C, EtOAc, rt. (quant.)2. XX, neat, 100 °C

CbzN

EtO2C

CO2Et

1. KOH, H2O/EtOH, ∆2. I2 , NaHCO3 , H2O

67% (4 steps)

CbzN

HO2C

OO

I

N NH2OH

1. thiophosgene,1. Ba2CO3 , DCM/H2O2. NaBH4 , MeOH/DCM3. KOH, H2O/tBuOH, ∆

1. EDC, Et3N, DCM, rt.2. Ac2O, pyr.

74%

43%

CbzN

OO

I

NH

O

AcO

1. Zn, HOAc, DCM2. CH2N2 , Et2O/DCM3. Lawesson's reagent,3. PhMe, ∆4. AIBN, H3PO2 , NEt3 ,4. 1-propanol/H2O, 90 °C N

NH

Cbz

AcO

36%

CO2Me

1. K2CO3 , MeOH2. MsCl, NEt3 , DCM3. Et3SiH, Pd(OAc)2 ,3. NEt3 , EtOH/EtOAc

79%

N

NH

CO2Me

Reissert reaction

Fukuyamaindole synthesis

CO2EtEtO2C

OEt


CbzN

EtO2C

CO2Et


67% (4 steps)

CbzN

HO2C

OO

I

54

52

53

51 ,

5655


62%

NCbz


NCbz

CO2EtEtO2C

OEt


CbzN

EtO2C

CO2Et


67% (4 steps)

CbzN

HO2C

OO

I

N NH2OH



74%

43%

CbzN

OO

I

NH

O

AcO


NH

Cbz

AcO

36%

CO2Me


79%

N

NH

CO2Me

Reissert reaction

Fukuyamaindole synthesis57


62%

NCbz


NCbz

CO2EtEtO2C

OEt


CbzN

EtO2C

CO2Et


67% (4 steps)

CbzN

HO2C

OO

I

N NH2OH



74%

43%

CbzN

OO

I

NH

O

AcO


NH

Cbz

AcO

36%

CO2Me


79%

N

NH

CO2Me

Reissert reaction



62%

NCbz


NCbz

CO2EtEtO2C

OEt


CbzN

EtO2C

CO2Et


67% (4 steps)

CbzN

HO2C

OO

I

N NH2OH



74%

43%

CbzN

OO

I

NH

O

AcO


NH

Cbz

AcO

36%

CO2Me


79%

N

NH

CO2Me

Reissert reaction



62%

NCbz


NCbz

CO2EtEtO2C

OEt


CbzN

EtO2C

CO2Et


67% (4 steps)

CbzN

HO2C

OO

I

N NH2OH



74%

43%

CbzN

OO

I

NH

O

AcO


NH

Cbz

AcO

36%

CO2Me


79%

N

NH

CO2Me

Reissert reaction

Fukuyamaindole synthesis 58

(±)-catharanthine (59)


62%

NCbz


NCbz

CO2EtEtO2C

OEt


CbzN

EtO2C

CO2Et


67% (4 steps)

CbzN

HO2C

OO

I

N NH2OH



74%

43%

CbzN

OO

I

NH

O

AcO


NH

Cbz

AcO

36%

CO2Me


79%

N

NH

CO2Me

Reissert reaction



Tota

l Syn

.

■ S. E. Denmark Org. Lett. 1999, 1, 1311–1314.

(+)-Casuarine — Denmark

12

■ Key features:■ 8 steps, 20% overall yield■ tandem [4+2] / [3+2] nitroalkene cycloaddition → creates 5 of 6 stereocenters present in the molecule

■ reductive alkylation with Raney Ni■ Fleming–Tamao oxidation

PhPh

O

CHO

1. TMSCl, Et3N,1. MeCN, 81 °C2. BzF, TBAF (2 mol-%),2. THF, 0 °C, 2 h

80%

PhPh

O

OBz

= G* O2NOBz

SnCl4 , PhMe, –78 °CN

OO

OBzOBz

OG*

OOTDS

SiMe2PhN

O

OBzOBz

OG*O

PhMe2Si

O

TDSO55%

(after HPLCpurification)

1. L-Selectride, 1. THF, –78 °C2. Ms2O, pyr., 1 h

84%

NO

OBzOBz

OG*O

PhMe2Si

HO

TDSO

H

HO

Ph Ph

1. Raney Ni, MeOH,1. H2 (18 bar)2. K2CO3

64%

N

PhMe2Si OH

OH

H

HO

OTDS

Hg(OTFA)2 , TFA, AcOH, AcOOHN

HO OH

OH

H

HO

OH

tandem [4+2] / [3+2]

reductive alkylationFleming-Tamao [O]

84%

60 61 6263

Ph SiPh

PhTPS

Si

DEIPS

Si

BIBS

Me Si

DTBMS

Si

DMIPS

Si

TDS

6465(+)-casuarine (66)

PhPh

O

CHO

1. TMSCl, Et3N,1. MeCN, 81 °C2. BzF, TBAF (2 mol-%),2. THF, 0 °C, 2 h

80%

PhPh

O

OBz

= G* O2NOBz

SnCl4 , PhMe, –78 °CN

OO

OBzOBz

OG*

OOTDS

SiMe2PhN

O

OBzOBz

OG*O

PhMe2Si

O

TDSO55%

(after HPLCpurification)


84%

NO

OBzOBz

OG*O

PhMe2Si

HO

TDSO

H

HO

Ph Ph

1. Raney Ni, MeOH,1. H2 (18 bar)2. K2CO3

64%

N

PhMe2Si OH

OH

H

HO

OTDS

Hg(OTFA)2 , TFA, AcOH, AcOOHN

HO OH

OH

H

HO

OH

tandem [4+2] / [3+2]

reductive alkylationFleming-Tamao [O]

84%


84%

NO

OBzOBz

OG*O

PhMe2Si

MsO

TDSO

H


Tota

l Syn

.

■ H. Heathcock Org. Lett. 1999, 1, 1315–1317.

(±)-Isoschizogamine — Heathcock

13

■ Key features:■ convergent synthesis, 8 steps (longest linear sequence), 7% overall yield■ take-home message: cyclizations, dehydration, clever use of Meldrum’s acid

KHMDS, Bu2BOTf,then 3-azidopropanal

O

O

O49%, d.r. 95:5

H2 , Pd/C

O

N3

OH

O O

N

OH

O O

MeO

MeO NO2

CHO

MeO

MeO NO2

OO

O

OH

O O

O NH

1. Meldrum's acid,1. piperidine (58%)2. XX , –40 °C

74%(2 steps)

PhMe, ∆MeO

MeO NO2

OH

O O

N

Od.r. 88:12

MeO

MeO NH2 O O

N

O1. [Ph(CF3)2CO]2SPh2 , 1. DCM, rt. (74%)2. NaBH4 , Cu(acac)2,2. EtOH, THF

LAH, THF,then H+ w/u

NH2

N

NH2

NN

O

OH

NH

OMeMeO

MeOOMe

N

NHO H

HOAc, H2O,reflux, 3 h

MeOOMe

N

NO HPDC, DCM

27%(4 steps)

67 68 69


O

O

O49%, d.r. 95:5

H2 , Pd/C

O

N3

OH

O O

N

OH

O O

MeO

MeO NO2

CHO

MeO

MeO NO2

OO

O

OH

O O

O NH


74%(2 steps)

PhMe, ∆MeO

MeO NO2

OH

O O

N

Od.r. 88:12

MeO

MeO NH2 O O

N



NH2

N

NH2

NN

O

OH

NH

OMeMeO

MeOOMe

N

NHO H


MeOOMe

N

NO HPDC, DCM

27%(4 steps)

70

69

7172


O

O

O49%, d.r. 95:5

H2 , Pd/C

O

N3

OH

O O

N

OH

O O

MeO

MeO NO2

CHO

MeO

MeO NO2

OO

O

OH

O O

O NH


74%(2 steps)

PhMe, ∆MeO

MeO NO2

OH

O O

N

Od.r. 88:12

MeO

MeO NH2 O O

N



NH2

N

NH2

NN

O

OH

NH

OMeMeO

MeOOMe

N

NHO H


MeOOMe

N

NO HPDC, DCM

27%(4 steps)

73

74a 74b75


O

O

O49%, d.r. 95:5

H2 , Pd/C

O

N3

OH

O O

N

OH

O O

MeO

MeO NO2

CHO

MeO

MeO NO2

OO

O

OH

O O

O NH


74%(2 steps)

PhMe, ∆MeO

MeO NO2

OH

O O

N

Od.r. 88:12

MeO

MeO NH2 O O

N



NH2

N

NH2

NN

O

OH

NH

OMeMeO

MeOOMe

N

NHO H


MeOOMe

N

NO HPDC, DCM

27%(4 steps)


O

O

O49%, d.r. 95:5

H2 , Pd/C

O

N3

OH

O O

N

OH

O O

MeO

MeO NO2

CHO

MeO

MeO NO2

OO

O

OH

O O

O NH


74%(2 steps)

PhMe, ∆MeO

MeO NO2

OH

O O

N

Od.r. 88:12

MeO

MeO NH2 O O

N



NH2

N

NH2

NN

O

OH

NH

OMeMeO

MeOOMe

N

NHO H


MeOOMe

N

NO HPDC, DCM

27%(4 steps)

76 (±)-isoschizogamine (77)


O

O

O49%, d.r. 95:5

H2 , Pd/C

O

N3

OH

O O

N

OH

O O

MeO

MeO NO2

CHO

MeO

MeO NO2

OO

O

OH

O O

O NH


74%(2 steps)

PhMe, ∆MeO

MeO NO2

OH

O O

N

Od.r. 88:12

MeO

MeO NH2 O O

N



NH2

N

NH2

NN

O

OH

NH

OMeMeO

MeOOMe

N

NHO H


MeOOMe

N

NO HPDC, DCM

27%(4 steps)

Gaich-Group Seminar Erik Stempel Te

xt

■ J. J. Li Name Reactions 2009, Springer Verlag Berlin, 339–340.■ K. C. Nicolaou Chem. Eur. J. 2004, 19, 5581–5606.

Excursus: Dehydrating Reagents■ Martin’s sulfurane

■ dehydrates 2° and 3° alcohols to give olefins, anti-elimination

!!

■ Burgess reagent ■ dehydration of 2° and 3° alcohols, usually proceeds via a syn-elimination

!!!

■ dehydration of amides to nitriles

!■ conversion of 1° alcohols to carbamates

14

PhS

Ph O(CF3)2PhO(CF3)2Ph

H

HO PhS

Ph O(CF3)2Ph

H

O

O(CF3)2Ph

PhSO

Ph

OH

Ph CF3

CF32

H

DPhH PhHO N CO2MeS

O

OEt3N H

DPhH PhOS N

CO2MeOO

Ph

H Ph

D

R NH2

O N CO2MeSO

OEt3N

R N

OS

NCO2Me

O O

HR N

R OH

N CO2MeSO

OEt3N

R OSN

CO2Me

OO

R NHCO2Me– SO3


Tota

l Syn

.

■ E. J. Corey Org. Lett. 1999, 1, 1503–1504.■ K. C. Nicolaou J. Am. Chem. Soc. 2000, 122 (13), 3071–3079.

(–)-Trichodimerol — Corey

15

■ Key features:■ biomimetic 2-step-synthesis■ cascades

38% (racemic)+ 35% regioisomer,

19% (after chiral HPLC)

OH

OH

O

1. Pb(OAc)4 , AcOH–DCM1. rt., 30 min2. chiral HPLC

10%

O

OH

O

NaOMe, MeOH, rt., 6 h,then NaH2PO4 ⋅ H2O

AcO

OHO

OOOH

OH

OHO

sorbicillin (78) 79 (–)-trichodimerol (80)

(–)-bisorbicillinol (83)

By-product via Diels-Alder reaction

OOOH

HO O

HO

HO

O

OH

R O

OHOH

O

R O

OH

81 82

OH

OO

HOO

OHO

OH

ketalization

Michael addition

OHO

OO OH

OH

OHO


Tota

l Syn

.

■ M. Toyota Org. Lett. 1999, 1, 1627–1629.

(±)-Methyl Gummiferolate — Toyota (I)

16

76%

OO

O

H

H

1. MeOH, ∆2. MeMgI, Et2O,2. then H2SO4

OO

H

H84%

1. LDA, THF, HMPA, –78 °C,1. then propargyl bromide2. LAH, Et2O3. Ac2O, pyr.

OAcHO

H

HSnBu3 , AIBN, PhH, ∆,then SiO2, DCM

OAcHO

H

homoallyl-homoallylradical rearrangement

OAcHO

HSnBu3

H

OAcHO

H

Bu3Sn

OAc

Bu3SnH

OH

H

OAcHO

HSnBu3

OAcHO

H

SnBu3

OAcHO

H

SnBu3 A

B

1. POCl3 , pyr.2. K2CO3 , MeOH99%

OHH

84 85 86 87

888990

91

91: 32%93: 50%

76%

OO

O

H

H


OO

H

H84%


OAcHO

H


OAcHO

H


OAcHO

HSnBu3

H

OAcHO

H

Bu3Sn

OAc

Bu3SnH

OH

H

OAcHO

HSnBu3

OAcHO

H

SnBu3

OAcHO

H

SnBu3 A

B


OHH

76%

OO

O

H

H


OO

H

H84%


OAcHO

H


OAcHO

H


OAcHO

HSnBu3

H

OAcHO

H

Bu3Sn

OAc

Bu3SnH

OH

H

OAcHO

HSnBu3

OAcHO

H

SnBu3

OAcHO

H

SnBu3 A

B


OHH

76%

OO

O

H

H


OO

H

H84%


OAcHO

H


OAcHO

H


OAcHO

HSnBu3

H

OAcHO

H

Bu3Sn

OAc

Bu3SnH

OH

H

OAcHO

HSnBu3

OAcHO

H

SnBu3

OAcHO

H

SnBu3 A

B


OHH

76%

OO

O

H

H


OO

H

H84%


OAcHO

H


OAcHO

H


OAcHO

HSnBu3

H

OAcHO

H

Bu3Sn

OAc

Bu3SnH

OH

H

OAcHO

HSnBu3

OAcHO

H

SnBu3

OAcHO

H

SnBu3 A

B


OHH

93 92

76%

OO

O

H

H


OO

H

H84%


OAcHO

H


OAcHO

H


OAcHO

HSnBu3

H

OAcHO

H

Bu3Sn

OAc

Bu3SnH

OH

H

OAcHO

HSnBu3

OAcHO

H

SnBu3

OAcHO

H

SnBu3 A

B


OHH

76%

OO

O

H

H


OO

H

H84%


OAcHO

H


OAcHO

H


OAcHO

HSnBu3

H

OAcHO

H

Bu3Sn

OAc

Bu3SnH

OH

H

OAcHO

HSnBu3

OAcHO

H

SnBu3

OAcHO

H

SnBu3 A

B


OHH

94

76%

OO

O

H

H


OO

H

H84%


OAcHO

H


OAcHO

H


OAcHO

HSnBu3

H

OAcHO

H

Bu3Sn

OAc

Bu3SnH

OH

H

OAcHO

HSnBu3

OAcHO

H

SnBu3

OAcHO

H

SnBu3 A

B


OHH


Tota

l Syn

.

■ M. Toyota Org. Lett. 1999, 1, 1627–1629.

(±)-Methyl Gummiferolate — Toyota (II)

17

OHH

1. DMSO, SO3 ⋅ pyr., 1. Et3N, DCM2. ,2. sBuLi, THF, –78 °C3. Ac2O, DMAP, DCM

OTES

OAcH

OTES

61% OAcH

O

1. PhMe, 200 °C2. TBAF, THF

87%H

OAcH

H

1. Me3S+(O)I–, NaH,1. DMSO, 50 °C (73%)2. BF3 ⋅ OEt2 , PhMe, –20 °C

Corey-Chaykovsky reaction+ Meinwald rearrangement

IMDA

O1. NaClO2 , KH2PO4 , 1. 2-methyl-2-butene, 1. tBuOH–H2O2. DBU, MeI, MeCN3. K2CO3 , MeOH, 50 °C

65%(4 steps)

OHH

MeO2CH

Pinnick [O]

OTMSH

MeO2C

H

1. TMSOTf, 2,6-lutidine, DCM2. LDA, THF, –78 °C, then HMPA, MeI

78%

MeO

H

MeO2C

H

Me

1. TBAF, THF2. angelic acid, Et3N, PhMe,2. 2,4,6-trichlorobenzoyl chloride

50%

O

Greene's esterification

94 95 96 97

■ Key features:■ 22 steps, 2% overall yield■ take-home message: homoallyl-homoallyl radical rearrangement, diene synthesis,

C1 elongation via Corey-Chaykovsky / Meinwald rearrangement sequence

9899(±)-methyl gummiferolate (100)

OHH

1. DMSO, SO3 ⋅ pyr., 1. Et3N, DCM2. ,2. sBuLi, THF, –78 °C3. Ac2O, DMAP, DCM

OTES

OAcH

OTES

61% OAcH

O

1. PhMe, 200 °C2. TBAF, THF

87%H

OAcH

H

1. Me3S+(O)I–, NaH,1. DMSO, 50 °C (73%)2. BF3 ⋅ OEt2 , PhMe, –20 °C

Corey-Chaykovsky reaction+ Meinwald rearrangement

IMDA

O1. NaClO2 , KH2PO4 , 1. 2-methyl-2-butene, 1. tBuOH–H2O2. DBU, MeI, MeCN3. K2CO3 , MeOH, 50 °C

65%(4 steps)

OHH

MeO2CH

Pinnick [O]

OTMSH

MeO2C

H

1. TMSOTf, 2,6-lutidine, DCM2. LDA, THF, –78 °C, then HMPA, MeI

78%

MeO

H

MeO2C

H

Me

1. TBAF, THF2. angelic acid, Et3N, PhMe,2. 2,4,6-trichlorobenzoyl chloride

50%

O

Greene's esterification


Tota

l Syn

.

■ M. T. Crimmins Org. Lett. 1999, 1, 2029–2032.

(+)-Laurencin — Crimmins

18

■ Features:■ straightforward synthesis, fast access to oxocene core■ 14 steps, 8% overall yield

88%OBn

OH NaH, THF,BrCH2CO2H

OBn

OHO2C

76%

PivCl, NEt3 , Et2O

LiN O

O

Bn, THF BnO

OO

N O

O

Bn

O

N O

O

Bn

OBnOH

H71%

Grubbs I,DCM, 40 °C94%

O

N O

O

Bn

OBnOH

H

1. DDQ, DCM, pH 7 buffer2. TIPSOTf, 2,6-lutidine, DCM3. LiBH4 , MeOH, Et2O4. Swern [O]

72%CHOOTIPSOH

HOTIPSO

HH

N

O

S

S

iBuTiCl4 , DIPEA,DCM, –78 °C

,

OH O

N S

S

iBuDiBAL,THF, –78 °C

OTIPSOH

H OH O

BrPh3PTIPS

nBuLi, THF, –50 °C,

OTIPSOH

H OH TIPS74%

(2 steps,5.5:1 E/Z)

OBrH

H OAc

1. Ac2O, pyr., 1. DMAP, DCM2. TBAF, THF3. CBr4 , P(octyl)3 ,3. PhMe, 70 °C

54%

NaHMDS, THF,allyl iodide, PhMe,–78 °C to –45 °C

83%(3.3:1)

101 102 103

104

105

88%OBn


OBn

OHO2C

76%

PivCl, NEt3 , Et2O

LiN O

O

Bn, THF BnO

OO

N O

O

Bn

O

N O

O

Bn

OBnOH

H71%


O

N O

O

Bn

OBnOH

H


72%CHOOTIPSOH

HOTIPSO

HH

N

O

S

S


,

OH O

N S

S


OTIPSOH

H OH O

BrPh3PTIPS


OTIPSOH

H OH TIPS74%

(2 steps,5.5:1 E/Z)

OBrH

H OAc


54%


83%(3.3:1)

106107

108

88%OBn


OBn

OHO2C

76%

PivCl, NEt3 , Et2O

LiN O

O

Bn, THF BnO

OO

N O

O

Bn

O

N O

O

Bn

OBnOH

H71%


O

N O

O

Bn

OBnOH

H


72%CHOOTIPSOH

HOTIPSO

HH

N

O

S

S


,

OH O

N S

S


OTIPSOH

H OH O

BrPh3PTIPS


OTIPSOH

H OH TIPS74%

(2 steps,5.5:1 E/Z)

OBrH

H OAc


54%


83%(3.3:1)

88%OBn


OBn

OHO2C

76%

PivCl, NEt3 , Et2O

LiN O

O

Bn, THF BnO

OO

N O

O

Bn

O

N O

O

Bn

OBnOH

H71%


O

N O

O

Bn

OBnOH

H


72%CHOOTIPSOH

HOTIPSO

HH

N

O

S

S


,

OH O

N S

S


OTIPSOH

H OH O

BrPh3PTIPS


OTIPSOH

H OH TIPS74%

(2 steps,5.5:1 E/Z)

OBrH

H OAc


54%


83%(3.3:1)

88%OBn


OBn

OHO2C

76%

PivCl, NEt3 , Et2O

LiN O

O

Bn, THF BnO

OO

N O

O

Bn

O

N O

O

Bn

OBnOH

H71%


O

N O

O

Bn

OBnOH

H


72%CHOOTIPSOH

HOTIPSO

HH

N

O

S

S


,

OH O

N S

S


OTIPSOH

H OH O

BrPh3PTIPS


OTIPSOH

H OH TIPS74%

(2 steps,5.5:1 E/Z)

OBrH

H OAc


54%


83%(3.3:1)

109

110 (+)-laurencin (111)

88%OBn


OBn

OHO2C

76%

PivCl, NEt3 , Et2O

LiN O

O

Bn, THF BnO

OO

N O

O

Bn

O

N O

O

Bn

OBnOH

H71%


O

N O

O

Bn

OBnOH

H


72%CHOOTIPSOH

HOTIPSO

HH

N

O

S

S


,

OH O

N S

S


OTIPSOH

H OH O

BrPh3PTIPS


OTIPSOH

H OH TIPS74%

(2 steps,5.5:1 E/Z)

OBrH

H OAc


54%


83%(3.3:1)


Tota

l Syn

.

■ D. J. Faulkner Nat. Prod. Rep. 1999, 16, 155–198.

Excursus: Some N. P. From Laurencia Species

19

■ red algae■ marine organisms that feed on Laurencia species have produced a diverse collection

of natural products containing medium ring ethers

OBrH

H OAc

(+)-Laurencin (115)

OBr HH

BrO

Bromifucin (114)

OBr

Cl

HH

Obtusenyne (113)

OH

Br

O• Br

HH

Laurallene (112)

O

O

Cl

•

HBr

HHBr

Obtusallene IV (116)

OBr

H HCl

(+)-Isolaurepinnacin (117)

O

Cl

BrH

(3Z)-13-Epipinnatifidenyne (118)

O

Br OHO

Scanlonenyne (119)


Tota

l Syn

.

■ L. E. Overman Org. Lett. 1999, 1, 2169–2172.

(–)-Batzelladine D — Overman (I)

20

R1

OH O

R2

SmI2 ,R3CHO

HOR1

R2

O

R3O

SmII

HOR1

R2

O

R3OH

H+

R1

OH

R2

O

R3

O

O

NH

R1

NH

H2NN+

NHH2N

R1

OH O

OR2MeONH

R1

NH

H2N

OMe

N

NHH2N

R1R2O

O

O

N

NH

R1R2O

O

N

N

NH

R1R2O

O

NH

99%MeO

OMe

O OH

C9H19SmI2 , EtCHO

Evans–Tishchenko reaction

MeO

OMe

OH O

C9H19

O

96%

1. HN3, Ph3P, DEAD2. K2CO3 , MeOH

MeO

OMe

N3 OH

C9H19

MeO

OMe

NH2 OH

C9H19

1. 4-NO2C6H4CO2H, 1. Ph3P, DEAD (89%)2. NaOH3. H2 , Pd/C

NN

H2N NH ⋅ HClDIPEA, MeOH

,

MeO

OMe

NH OH

C9H19

NH ⋅ HCl

H2N

AcOH–H2O, rt., thenO O

O(CH2)4NHCbzmorholinium acetate,Na2SO4 , CF3CH2OH, 70 °C

,

NH

N

OH

C9H19

NH ⋅ HOAc

O

HN(CH2)4OH HCbz

55% (4 steps)

Biginelli reaction

120 121 122

124

123125

99%MeO

OMe

O OH

C9H19SmI2 , EtCHO


MeO

OMe

OH O

C9H19

O

96%


MeO

OMe

N3 OH

C9H19

MeO

OMe

NH2 OH

C9H19


NN


,

MeO

OMe

NH OH

C9H19

NH ⋅ HCl

H2N



,

NH

N

OH

C9H19

NH ⋅ HOAc

O

HN(CH2)4OH HCbz

55% (4 steps)

Biginelli reaction

99%MeO

OMe

O OH

C9H19SmI2 , EtCHO


MeO

OMe

OH O

C9H19

O

96%


MeO

OMe

N3 OH

C9H19

MeO

OMe

NH2 OH

C9H19


NN


,

MeO

OMe

NH OH

C9H19

NH ⋅ HCl

H2N



,

NH

N

OH

C9H19

NH ⋅ HOAc

O

HN(CH2)4OH HCbz

55% (4 steps)

Biginelli reactionBernatowicz’ guanidine synthesis

126


O(CH2)4NHCbzmorpholinium acetate,Na2SO4 , CF3CH2OH, 70 °C

,

NH

N

OH

C9H19

NH ⋅ HOAc

O

HN(CH2)4OH HCbz

55% (4 steps)

Biginelli reaction


Tota

l Syn

.

■ L. E. Overman Org. Lett. 1999, 1, 2169–2172.

(–)-Batzelladine D — Overman (II)

21

(–)-batzelladine D bistrifluoroacetate (132)

NH

N

OH

C9H19

NH ⋅ HOAc

O

CbzHN(CH2)4OH H 1. MsCl, Et3N

2. Et3N , CHCl3 , ∆

NH

N

NH

O

CbzHN(CH2)4OH H

60%

Cl–C9H19 N

H

N

NH

O

ROH H

Cl–C9H19

NaCNBH3 ,AcOH–MeOH

92%

NH

N

NH

O

ROH H

Cl–C9H19

badyields

H2 , Rh/Al2O3 ,HCO2H, MeOH–H2O

NH

N

NH

O

CF3CO2H ⋅ H2N(CH2)4OH H

C9H19NH

N

NH

O


CF3CO2–

C9H19

NH

N

NH

O

OH H

C9H19

HN

NH2

H2N

CF3CO2–

NN

H2N NH ⋅ HClDIPEA, DMF

,

CF3CO2–

CF3CO2–

NH

N

OH

C9H19

NH ⋅ HOAc

O


2. Et3N , CHCl3 , ∆

NH

N

NH

O

CbzHN(CH2)4OH H

60%

Cl–C9H19 N

H

N

NH

O

ROH H

Cl–C9H19


92%

NH

N

NH

O

ROH H

Cl–C9H19

badyields


NH

N

NH

O


C9H19NH

N

NH

O


CF3CO2–

C9H19

NH

N

NH

O

OH H

C9H19

HN

NH2

H2N

CF3CO2–

NN


,

CF3CO2–

CF3CO2–

■ Key Features:■ 13 steps, 6% overall yield■ Evans-Tishchenko reaction■ tethered Biginelli condensation■ guanidine synthesis

130131

NH

N

OH

C9H19

NH ⋅ HOAc

O


2. Et3N , CHCl3 , ∆

NH

N

NH

O

CbzHN(CH2)4OH H

60%

Cl–C9H19 N

H

N

NH

O

ROH H

Cl–C9H19


92%

NH

N

NH

O

ROH H

Cl–C9H19

badyields


NH

N

NH

O


C9H19NH

N

NH

O


CF3CO2–

C9H19

NH

N

NH

O

OH H

C9H19

HN

NH2

H2N

CF3CO2–

NN


,

CF3CO2–

CF3CO2–

130: 27%131: 42%

75%

126 127 128

129

NH

N

OH

C9H19

NH ⋅ HOAc

O


2. Et3N , CHCl3 , ∆

NH

N

NH

O

CbzHN(CH2)4OH H

60%

Cl–C9H19 N

H

N

NH

O

ROH H

Cl–C9H19

Na(CN)BH3 ,AcOH–MeOH

92%

NH

N

NH

O

ROH H

Cl–C9H19

badyields

Gaich-Group Seminar Erik Stempel M

etho

d.

Selected Methodologies

22


etho

d.

■ K. C. Nicolaou Org. Lett. 1999, 1, 883–886.■ A. Mori Org. Lett. 1999, 1, 299–301.

Miscellaneous (I)■ Synthesis of Hindered α-Diaozoketones

■ mild one-pot protocol for the conversion of sterically demanding carboxylic acids into α-diazoketones via acyl mesylates

!■

!■ Palladium-Catalyzed Cross-Coupling of Silanols with Organic Halides

■ Pd-catalyzed cross-coupling of silanols is achieved by the addition of Ag₂O as an activator

■

■ scope: R and R’ are almost exclusively electron-rich aryl rests

23

RO

OHEt3N (10.0 eq.),MsCl (5.0 eq.), MeCN, –10 °C, 10 min R

O

O S MeO

O

then CH2N2in Et2O, 0 °C R

ON2

OSCH2

Ovia

one pot

133 134 135

R SiMe2OH R' I

cat. Pd(PPh3)4 , Ag2O,THF, 60 °C, 36 h

R R'

136 137 138


etho

d.

■ L. Buchwald Org. Lett. 1999, 1, 35–37.■ V. H. Rawal Org. Lett. 1999, 1, 673–676.

Miscellaneous (II)■ Pd-Catalyzed Cyclization Reactions of Secondary Amides and Carbamates

■ five-, six-, and seven-membered rings are formed efficiently from secondary amide or secondary carbamate precursors

■ ligands which are capable of chelation (e.g. bisphosphines) are essential!

■ !!!!

■ Regiocontrolled Synthesis of Carbocycle-Fused Indoles ■ two-step procedure:1) regiospecific arylation of silyl enol ether with o-NO₂Ph(IPh)⁺F⁻

2) reduction of the aromatic nitro group with TiCl₃ followed by 2) spontaneous aromatization/indolization !

■

24

Pd(OAc)2 (3.3 mol-% Pd),Cs2CO3 (1.4 eq.),Phosphine-Ligand (5.0 mol%),PhMe, 100 °C, 20–36 h

BrO

NHBn

Br

NHRR = Ac, Cbz, Boc, n = 1–3,

Ligand: MOP, DPEphos, Xanthphos

n

n

n

NBn

O

n

NR

yields: 79–95%139

140

141

142

OTMS

n

R

NO2

IPhF–

1.

2. TiCl3 , H2O, NH4OAc, acetone

n

RNH

R = H, Me, OMe; n = 0–1

yields: 60–89%

143

144

145


etho

d.

■ G. Keck Org. Lett. 1999, 1, 411–413.■ B. Singaram Org. Lett. 1999, 1, 799–801.

Miscellaneous (III)■ A Versatile Preparation of α,β-Unsaturated Lactones from Homoallylic Alcohols

■ new method for the one-pot synthesis of α,β-unsaturated lactones from β-acetoxy aldehydes by reaction with the lithium enolate of methyl acetate!

■

!!

■ N,N-Dialkylaminoborohydrides — Facile Reduction of N-Alkyl Lactams ■ five- and six-membered lactams are reduced to the corresponding cyclic amines using

lithium dimethylaminoborohydride (LiH₃BNMe₂)!

■

!■ selective reductions:

25

yields: ~50–90%R

AcO OLi

OMe1. O32.

R

O

O

146 147

yields: 80–96%NR

O

n

1.5 eq. LiH3BNMe2 ,THF, 65 °C, 2 h

R = alkyl, aryl; n=0–1NR

n

148149

N

OCO2Me

Bn

2.5 eq. LiH3BNMe2 , THF, 65 °C, 2 h

1.1 eq. LiH3BNMe2 , THF, –10 °C, 2 h

2.2 eq. 9-BBN, THF, 65 °C, 1 h

N

O

Bn OH

NBn OH

NCO2Me

Bn150

151

152

153


etho

d.

■ A. Fernàndez-Mateos Org. Lett. 1999, 1, 607–609.

Miscellaneous (IV)■ Radicals from Epoxides. Intramolecular Addition to Aldehyde and Ketone Carbonyls

■ Titanocene dichloride reacts with epoxides by C—O homolysis■ resultant radicals undergo intramolecular addition to aldehydes and ketones to afford

cycloalkanols in good yield

■

!!

■ mechanism:

!!!!!!

■ comment: small scope, but looks promising with additional optimization work

26

OHR

OH

R

OO

Cp2TiCl2 R

OOH

common minor by-product154 155

OHR

OH

R

OO

Cp2TiCl2 R

OOH

common minor by-product

156

R

OO

R

OO[Ti] [Ti]OR

O [Ti]OR

O[Ti] OHR

OHw/u

R

OO[Ti][Ti]

R

OO[Ti]

– H[Ti]

w/uR

OOH

157 158a 158b 158c 159

158d 158e 160


etho

d.

■ J. Wood Org. Lett. 1999, 1, 371–374.■ M. E. Jung Org. Lett. 1999, 1, 367–369.

Miscellaneous (IV)■ Rhodium Carbenoid-Initiated Claisen Rearrangement

■ reaction of α-diazoketones with allylic alcohols in the presence of Rh(II) catalysts■ intermediate undergoes Claisen rearrangement to furnish α-hydroxyketones

■

!!!

■ Facile Preparation of Allenic Hydroxyketones ■ treatment of propargylic alcohols with α-diazoketones in the presence of Rh(II) catalysts

yields allenic hydroxyketones■ mechanistic proposal: intermediate undergoes [2,3]-sigmatropic rearrangement

27

R1

OR2

N2

Rh2(OAc)4 , PhH, ∆R3 R4

HO

R5

,

O

R4

R3

O

R1

R2R5

M O

R1•R3

R4R2 OH

R5

[2,3]

162

R1

OR2

N2

R5R4

OH

R3

Rh2(OAc)4 , PhH, ∆

,

OR3

R4

R5

OH

R1

R2

[3,3]R3

R4

R5

HO R1R2

O

161 163 164

165

166

167 168


etho

d.

■ G. Sabitha Org. Lett. 1999, 1, 1701–1703.

A Mild, Efficient, Inexpensive, and Selective Cleavage of Primary TBMDS Ethers by Oxone® in aq. Methanol■ Oxone® in a 50% aqueous methanolic solution cleaves primary alkyl and aryl TBDMS

ethers■ high selectivity

■ deprotection of primary TBDMS ethers within few hours■ secondary, tertiary and phenolic TBDMS ethers are unaffected■ deprotection of TBDMS ethers possible in the presence of TPDPS ethers and certain

acid-labile protecting groups (THP, N-Boc, …)■ mild conditions, inexpensive■ mechanism unknown

28

■ own experience:■ full conversion■ easy handling, no precautions required■ clean product, no purification necessary■ proceeds even faster with ultrasonic!

> 88%R OTBDMS

Oxone®,MeOH–H2O (1:1)

R OH

169 170


Den

kspo

rt

■ K. Cha Org. Lett. 1999, 1, 523–525.■ T. Fujimoto Org. Lett. 1999, 1, 427–430.

Easy “Denksports”

29

H

H

OH

OTMSPh

OTBSO CO2Me

Cl

Cl

OCl

Et3N, CF3CH2OH,then Zn, MeOH

,

SO Ph

PF6

2.0 eq. LiHMDS,THF, rt.,

O

OAc

thenO

Me

H

SPhO

171 173

174

172

175 176 177

Thanks for your attention.

Questions?


Solu

tions

■ K. Cha Org. Lett. 1999, 1, 523–525.■ T. Fujimoto Org. Lett. 1999, 1, 427–430.

Solutions

31

OTBSO CO2Me

Cl

Cl

OCl

Et3N, CF3CH2OH,then Zn, MeOH

,

OTBSO CO2Me

Cl ClO

[4+3] oxyallyl cycloadditionO

Y

Y

O

CO2Me

OTBS

Y = ClY = HZn, MeOH

O

SO Ph

PF6

2.0 eq. LiHMDS,THF, rt.,

O

OAc

then SO Ph

O

OAcSN2'

SO Ph O

LiHMDSS

O Ph O

S(O)PhOCorey-Chaykovsky likeS(O)PhO

Me

H

SPhO

Journal Years in Review: Organic Letters 1999 · 2017. 3. 24. · (vi) T. Nikaoido Org. Lett. 1999,...

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Transcript of Journal Years in Review: Organic Letters 1999 · 2017. 3. 24. · (vi) T. Nikaoido Org. Lett. 1999,...