Literature review

• Angewandte Chemie Int. Ed. 2007, Issues 42-48

2008, Issues 1-5

• Synlett

2007, Issues 17-20

2008, Issues 1-2

Nicolas Demoulin 24/01/08

2

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

Metal-Catalytic HydrogenationP. A. Chase, G. C. Welch, T. Jurca, and D. W. Stephan*

• Hydrogenation is one of the most important catalytic

method in synthetic organic chemistry (lab & industry)

• H2 cleanest reducing agent

• Addition of hydrogen to unsaturated organic

compounds usually mediated by homogeneous or

heterogeneous transition-metal catalysts (Ni, Pd,

Ru, Rh….)

3

Only few hydrogenations involve non-transition-metal catalysts

O OHKOtBuT > 200°CP(H2) > 100 bar

Albrecht Berkessel, Thomas J. S. Schubert, and Thomas N. Müller J. Am. Chem. Soc. 2002, 124, 8693-8698.

P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2004, 116, 5248-5286; Angew. Chem. Int. Ed. 2004, 43, 5138.D. Menche, J. Hassfeld, J. Li, G. Menche, A. Ritter, S. Rudolph, Org. Lett., 2006, 8, 741-744.D. Menche, F. Arikan, Synlett, 2006, 841-844.

R2

R1

O

R3

O

R4H2N Ar

R2

R1

O

NH

EtO2C CO2Et

R3

HN

R4

Ar

Organocatalyst Hydrogen source

Thiourea cat.

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

4

“Frustrated Lewis pairs”

• Bulky Lewis acid and base no Lewis adduct

G. C. Welch, R. R. S. Juan, J. D. Masuda, D. W. Stephan Science 2006, 314, 1124 .Gregory C. Welch and Douglas W. Stephan J. Am. Chem. Soc. 2007, 129, 1880 -1881.

• F F

F F

R2P B(C6H5)2

H H Air & moisture stable Metal-free hydrogenation catalysts of imines,

nitriles and aziridines

B(C6F5)3 PR3

H2, rtHB(C6F5)3R3PH

R= tBu or 2,4,6-Me3C6H2

F F

F F

R2P B(C6H5)2

H2, rt

F F

F F

R2P B(C6H5)2

H H

T>100°C

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

5

Reduction of Imines

Entry Substrate Cat T(°C)P(H2)

atmt(h)

Yield(%)

Product

1 1 80 1 1 79

2 2 80 1 1 98

3 1 120 5 10.5 97

4 2 120 5 16 87

5 1 140 5 1 88

6 1 120 5 48 5

7 1 120 5 46 57

PhN

PhPh

NHtBu

Ph

NHSO2Ph

Ph

NHPh

Ph

Ph

PhN

Ph

B(C6F5)3NH

Ph

PhB(C6F5)3

Ph H

NR

HNR

Ph

Cat 5-10%molin tolueneH2 1-5 atm

PhN

PhNH

Ph

Ph

PhN

tBu

PhN

SO2Ph

R= tBu (1) R= 2,4,6-Me3C6H2 (2)

F F

F F

R2P B(C6H5)2

H H

• Bulky imines reduction (1-5)

• Electron poor imines less reactive • Less bulky imines react with the catalyst forming a strong adduct and inhibit it

• Problem solved in presence of B(C6F5)3

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

Basicity of N center at stake

6

Reaction with nitriles and aziridines

Entry Substrate t(h)Yield(%)

Product

1 MeCN 48 0

2 24 75

3 24 84

4 48 99

5 1.5 98

6B(C6F5)3-isonitrile

- 0 -

Cat (1) 5-10 %molin toluene

120°C, H2 5 atmR CN R

NH2

R= tBu (1)

F F

F F

R2P B(C6H5)2

H H

MeCNB(C6F5)3

NH2

NH2B(C6F5)3

NH2B(C6F5)3PhCNB(C6F5)3Ph

B(C6F5)3CN

CNB(C6F5)3NH2

B(C6F5)3

B(C6F5)3

NH2

N

Ph Ph

Ph

Ph

HN

Ph

Ph

• Nitrile fonction clearly interacts with catalyst

• Problem solved in presence of activating B(C6F5)3

• Ring opening of unactivated

aziridines

• Activated isonitriles don’t react

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

7

Mechanism for Bulky Imines and Aziridines

Ph H

NtBu

F F

F F

Cy3P B(C6H5)2

Hno

adduct

1 eq. 1 eq.

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

F F

F F

R2P B(C6H5)2

F F

F F

R2P B(C6H5)2

H H

H

Ph H

NR'

Ph H

NR'H

F F

F F

R2P B(C6H5)2

H21) Proton transfer

2) Hydride attack

Ph

HNR'

N

Ph

Ph Ph

or

N

Ph

Ph Ph

Hor

Ph

Ph

HN

Ph or

F F

F F

R2P B(C6H5)2

H

Ph

H2NR'

Ph

Ph

H2N

Ph or

WEAK ADDUCT

• The bulkier the imine is, the quicker the reaction is

• 31P, 11B, 19F NMR

8

Mechanism for activated Imines and Nitriles

• Nitriles or less bulky imines• Protection with B(C6F5)3

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

F F

F F

R2P B(C6H5)2

F F

F F

R2P B(C6H5)2

H H

Ph H

NR'

F F

F F

R2P B(C6H5)2

H2

2) Proton transfer

1) Hydride attack

Ph

NR'

(C6F5)3B

Ph

NR'(C6F5)3B

R'' CNor

R''N B(C6F5)

3or

R''N B(C6F5)3

(C6F5)3BH

H

or

B(C6F5)3

H

9

Angew. Chem. Int. Ed. 2007, 46, 8869-8871Asymmetric Sommelet-Hauser Rearrangement of

N-Benzylic Ammonium Salts Eiji Tayama*, and Hiroshi Kimura

• C-N into new C-C

• Competion usually observed between Stevens & Sommelet-Hauser (SH) rearrangements

• So far, limited asymmetric SH rearrangement

Eiji Tayama*, Shintaro Nanbara and Takeshi Nakai, Chem. Lett . 2006, 35, 478-479.

N

CO2tBu

CO2tBu

N

CO2tBu

CO2tBu

N

CO2tBu

CO2tBu

CsOH1,2-dichloroethane

-10°C, 24h

tBuOKTHF

-40°C, 6h

1,2 Stevens

2,3 Sommelet-Hauser

42%, ee > 99%

96%, ee > 99%α-aryl proline tert-butyl ester

α-benzylated proline tert-butyl ester

10

Asymmetric SH rearrangementPara

Ortho

Meta

R1 T(°C) t(h) yield dr S/R

COOtBu -40 4 95 >98:2

COOMe -60 8 85 >98:2

COPh -60 8 82 >98:2

CN -60 8 82 97:3

CF3 -60 15 93 >98:2

H -40 15 46 >98:2

OMe -40 15 0 -

• Good yields , good d.r • EW groups accelerate the reaction

N COOR* N COOR*tBuOKTHF

N COOR*

R1 = CN, -60°CR1 = CF3, -40°C

67%, S/R > 98/290%, S/R > 98/2

6%, S/R > 98/20%

R1

R1

R1Br

N COOR* N COOR*tBuOKTHFR1

R1

N COOR*

R1

R1 = CN, -60°C, 8hR1 = CF3, -60°C, 15h

86%, S/R = 98/289%, S/R > 98/2 0%

Br

COOR* =

COO

Ph

Angew. Chem. Int. Ed. 2007, 46, 8869-8871

α-aryl N,N-dimethylglycine ester

N COOR*

R1

N COOR*

R1

tBuOKTHFBr

11

Mechanism

Concerted stereoselective [2,3] S-H Rearrangement

NO-

O

Ph

O

ON

Ph

O

ON

Ph

2,3 S-H

(S) (S)

R1

NO-

O

PhR1

O

ON

Ph

(S)

Ortho

MetaR1

NO-

O

Ph

R1

O

ON

Ph

(S)

R1

O

ON

Ph

(S)

>>

Angew. Chem. Int. Ed. 2007, 46, 8869-8871

12

• Wide variety of bioactive natural products with indoles framework

• Numerous methods to synthetize indoles

Angew. Chem. Int. Ed. 2008, 47, 350-352One-Pot Multicomponent Synthesis of Indoles

from 2-Iodobenzoic Acid Olivier Leogane and Hélène Lebel

I

COOH

I

NC

O

NucR1

O

R2

R1

R2 NR1

R2

ONuc

Curtius rearrangement / palladium-catalysed indolization

13

Study of the reaction

• Palladium-catalysed indolization(1)

Without LiCl no reaction

With excess of LiCl, low yield

I

NHCbz

Pr

PrNH

Pr

Pr

NCbz

Pr

Pr

Pd(OAc)2 (5%mol)LiCl (1 eq)DMF, 120°C

Na2CO3 (1.1 eq.), 3hNa2CO3 (3 eq.), 16h

traces85%

48%0%

I

COOH NH

Pr

Pr1. CbzCl, NaN3/DMF,75°C tBuONa (15 mol%)2. Pd(OAc)2 (5 mol%), base, LiCl DMF, 120°C, Pr Pr

• One-Pot Curtius rearrangement(2) / Palladium-catalysed indolization

Entry LiCl Base (eq.) Alkyne (eq.) Yield (%)

1 yes K2CO3 (5) 5.0 29

2 no Na2CO3 (1.5) 1.5 71

3 no K2CO3 (1.5) 1.5 73

4 no Cs2CO3 (1.5) 1.5 40

5 no Na2CO3 (3) 3.0 84

6 no K2CO3 (3) 3.0 73

NaCl formed during the Curtius rearrangement

Synergic effect

Angew. Chem. Int. Ed. 2008, 47, 350-352

(1) Chris H. Senanayake Org. Lett. 2006, 8, 3271-3274

(2) Hélène Lebel and Olivier Leogane, Org. Lett. 2006, 8, 5717-5720

14

Scope of the reaction

I

COOH NH

R1

R2

1. CbzCl, NaN3/DMF,75°C tBuONa (15 mol%), 5h2. Pd(OAc)2, base, Coupling agent DMF, 120°C, 16h

EntryCoupling agent

Product Yields (%)

1 77

2 56

3 82

4 50

5 53

6 56

Ph PhNa2CO3

NH

Ph

Ph

NH

Me

tBu

tBu MeNa2CO3

Ph TMSNa2CO3 N

H

TMS

Ph

PhCHO

DABCO

CHO

DABCO

BnO

DABCO

O

NH

Bn

NH

OBn

NH

• Unsymmetrical alkynes

Good yields and regiocontrol

• Moderate yields with aldehydes and ketones

Angew. Chem. Int. Ed. 2008, 47, 350-352

15

I

COOH NR1

R11. PhOCOCl, NaN3 tBuONa (15 mol%) NMP,75°C, 5h2. R2R3NH, 75°C, NMP, 3h3. Pd(OAc)2,120°C, 16h

R1 R1O

NR2

R3

Scope of the reactionSynthesis of indole N-carboxamide derivatives

NPh

Ph

ON O

NPh

Ph

ON

NPr

Pr

ON

NPh

Ph

ON

NPr

Pr

ONH

PhMe

NPr

Pr

ONH Ph

64% 54%

59%

68%

62% 39%

I

COOH

I

NC

O

R1 R1

NH

I

ON

Curtius Rearrangement

NR3H

R2

R2

R3

N

ON

R2

R3

R1

R1

Angew. Chem. Int. Ed. 2008, 47, 350-352

16

• Diaryl ether widely present in bioactive compounds

• Synthesized using transition-metal-catalyzed cross-coupling reactions (Co, Pd…)

• Fe Chemistry: challenging, less expensive, less poluting, attractive industrial prospects

Angew. Chem. Int. Ed. 2008, 47, 586-588Iron-Catalysed C-O Cross-Coupling of Phenols

with Aryl Iodide Olivia Bistri, Arkaitz Correa and Carsten Bolm*

NNH

NN Ar

FeCl3 (10 mol%)dmeda (20 mol%)K3PO4, toluene135°C, 24h

ArX

FeCl3 (10 mol%)dmeda (20 mol%)K3PO4, toluene135°C, 24h

IR NuH

NuR

Arkaitz Correa and Carsten Bolm*, Angew. Chem. Int. Ed. 2007, 46, 8862-8865.

17

Study of the reaction

• [Fe]: FeCl3, FeCl3.6H2O, Fe(acac)3

• Base: K3PO4, Cs2CO3, NaOtBu, NaHCO3, Na2CO3, KOAc

• Solvent: toluene, MeCN, dioxane, DMF

• Ligand:

OOH I [Fe] (0.1 eq)ligand (0.2 eq)base, solvent135°C,20h

Interplay between ligand, base, solvent strongly depend on the substrate

OOH IFeCl3 (10 mol%)dmeda (20 mol%)K3PO4, toluene135°C, 24h

0%

Optimized conditions:

FeCl3 (10 mol%)

L3 (20 mol%)

CsCO3 (2 eq)

DMF, 135°C

MeHN NHMeN COOH.HCl tBu

O

tBu

O

NH2H2N N NNH

COOH

L3L2L1

L4 L5 L6

Angew. Chem. Int. Ed. 2008, 47, 586-588

18

Scope of the reaction

O

Ph

O

O

O

O

Me Me

MeO

O

tBu

O

O

O

F

O

Cl

O

O2N

85% 95% 74%

95% 95% 84%

87%99%92%

0%

• Excellent yields with electron-rich or electron-poor phenols

• Reaction fails to work when the phenol incorporates strongly electron-withdrawing groups

OOH IFeCl3 (10 mol%)L3 (20 mol%)Cs2CO3, DMF135°C, 20h

R R

tBu

O

tBu

OL3

Angew. Chem. Int. Ed. 2008, 47, 586-588

19

Scope of the reaction

tBu

O

tBu

OL3

OOH XFeCl3 (10 mol%)L3 (20 mol%)Cs2CO3, DMF135°C, 20h

R

X=ClX=BrX=I

0%69%85%

OOH IFeCl3 (10 mol%)L3 (20 mol%)Cs2CO3, DMF135°C, 20hR

R

O

O

O

O

O

O

O

50% 0%

78%

80%78%90%

87%

Cl OMe

Cl COOEt NO2

O O

90% 87%

Me Cl

O

78%

FOMe Me

Angew. Chem. Int. Ed. 2008, 47, 586-588

20

Some good reading

• Protection-Group-Free Formal Synthesis of Platensimycin.

J. Mulzer, Angew. Chem. Int. Ed. 2007, 46, 8074-8075.

• Catalytic Enantioselective Passerini Three-Component reaction.

MX. Wang and J. Zhu, Angew. Chem. Int. Ed. 2008, 47, 388-391.

• Cyclic triolborates: Air and Water stable Ate complexes of Organoboronic Acids.

Y. Yamamoto and N. Miyaura, Angew. Chem. Int. Ed. 2008, 47, 928-931.

• Synthesis of α-Ketoamides by a Molecular-Sieves-Promoted Formal Oxidative

Coupling of Aliphatic Aldehydes with Isocyanides.

JM. Grassot, G. Masson and J. Zhu, Angew. Chem. Int. Ed. 2008, 47, 947-950.

• A Stable, Convertible Isonitrile as a Formic Acid Carbanion Equivalent and Its Application in

Multicomponent Reactions.

L.A. Wessjohann, Synlett. 2007, 20, 3188-3192.

• Novel Ir-SYNPHOS® and Ir-DIFLUORPHOS® Catalysts for Asymmetric Hydrogenation of Quinolines.

JP. Genêt, K. Mashima, V. Ratovelomanana-Vidal, Synlett 2007, 17,2743-2747.