Jean Pierre Genêt

RECENT DEVELOPMENTS OF PALLADIUM(0) CATALYZED REACTIONS IN AQUEOUS MEDIUM

Abstract Palladium cross-coupling reactions: Heck, Sonogashira, Tsuji-Trost, Suzuki, Stille as well as protecting group chemistry in aqueous media are presented. The excellent compatibility of water-soluble palladium catalysts offer new opportunities (mild conditions, new selectivity). In most of the reaction catalyzed by palladium in water described in this review, careful selection of reaction conditions, co-solvents and catalysts, is very important for long life catalyst and new selectivities. The palladium catalyzed reactions with water-soluble phosphines (e.g. sulfonated phosphines) provide advantages of the two phase aqueous system: easy separation of the products and recycling the expensive palladium. This technique has increased the potential of modern palladium catalysis.

Efficient asymmetric synthesis of optically pure tertiary mono and diphosphine ligands

The oxazaphopholidine borano complex 3, prepared in one step from ephedrine, reacts with alkyl and aryl lithium compounds to afford regio and stereoselectively the corresponding aminophosphine complexes 4. Acid methanolysis of 4 leads to the phosphinite borane complexes 5 which are used for the preparation of the mono and diphosphine boranes 6, 8, and subsequently the corresponding phosphines 7, 9 alter decomplexation with Et2NH. The preparation of (+) and (−)-PAMP 7a, DIPAMP 9a or β-BNPE 9b from the same complex 3 is described.

Enantioselective hydrogenation reactions with a full set of preformed and prepared in situ chiral diphosphine-ruthenium (II) catalysts.

Abstract The new class of 2-methylallyl ruthenium chiral diphosphines 1 are efficient in asymmetric hydrogenation of α,β unsaturated acids and allylic alcohols. The related chiral halogen-containing ruthenium catalysts 2 are prepared from 1 or in situ from (COD)Ru(η) 3 -(CH 2 ) 2 CHCH 3 ) 2 by ligand exchange with the chelating diphosphine followed by protonation (HX) in acetone. This procedure allows rapid screening of chiral phosphines, such as Diop, Chiraphos, Cbd, Bppm, Binap, β-glucophos, Biphemp, MeO-Biphep, Me-Duphos, in ruthenium mediated hydrogenations of prochiral substrates. A high efficiency is displayed by Ru-catalysts having atropisomeric ligands (e.e. up to 99%), and a C 2 symmetric bis(phospholane) has also emerged as a valuable ligand (Me-Duphos, e.e. up to 87% not optimized). Asymmetric hydrogenation of β-keto esters can be conducted under quite mild conditions (4 atm. of H 2 , 50°C, e.e. up to 99%), β-keto esters having a disubstituted double bond are also hydrogenated chemoselectively to unsaturated chiral alcohols under controlled conditions with excellent optical purities.

Asymmetric synthesis. Practical production of D and L threonine. Dynamic kinetic resolution in rhodium and ruthenium catalyzed hydrogenation of 2-acylamino-3-oxobutyrates.

Abstract Enantioselective syntheses of D and L threonine are described. Racemic methyl and ethyl 2-acylamino-3-oxobutyrate 1 were synthesized from the corresponding acetoacetates 6 and then hydrogenated stereoselectivety via dynamic kinetic resolution with various chiral P * P Rh (I) 8 and Ru (II) 10 catalysts to give syn optically active alcohols which could be converted by hydrolysis and treatment with propylene oxide into threonine. The best results were obtained using (−) CHIRAPHOS Ru and (+) BINAP Ru as catalysts, in the hydrogenation step leading respectively to D threonine (ee: 99 %) and L threonine (ee: 94 %) in 26–34 % overall yields.

Novel, general synthesis of the chiral catalysts diphosphine-ruthenium (II) diallyl complexes and a new practical in situ preparation of chiral ruthenium (II) catalysts

Abstract A general and new synthesis of hexacoordinate chiral 1-[2-methylallyl]Ru II 2 complexes is presented. This synthesis uses the very accessible CODRu(2-methylallyl) 2 complex as starting material. These complexes (P*P)Ru(η 3 -(CH 2 ) 2 CCH 3 ) 2 (e.g. P*P=DIOP, CBD, DEGUPHOS, BINAP, BIPHEMP, CHIRAPHOS, PROPHOS, DIMPC, BPPM, BDPP, DIPAMP, DIPAMPSi, β-PO-OP) have been characterized spectroscopically. X-Ray structures were obtained for (S,S)-DIOP and (S,S)-CHIRAPHOS. They are suitable for the preparation of chiral dihalide ruthenium (II) catalysts. In addition, we have found that it was possible to prepare these same catalysts directly in situ from (COD)Ru(η 3 -(CH 2 ) 2 CCH 3 ) 2 by adding 1-1.3 equiv. of the appropriate chiral ligand in the presence of HX in acetone at room temperature.

Asymmetric synthesis of phosphinates, phosphine oxides and phosphines by Michaelis Arbuzov rearrangement of chiral oxazaphospholidine

Abstract A general approach to asymmetric synthesis of high optically active tertiary organophosphorus compounds is described. Oxazaphospholidine 3 reacts with alkyl halide to give regio and stereoselectively the corresponding phosphinamide 4 . Methyl phenyl phosphinamide 4a is used for the preparation of methyl phenyl phosphinate 5a with ee > 96%. The preparation of (+) and (−) - PAMP or DIPAMP from 3 is described.

SELECTIVE DEPROTECTION OF ALLYL AMINES USING PALLADIUM

Mono and diallylamines can be cleaved using Pd(0) catalyst and 2-mercaptobenzoic acid as nucleophile. This methodology has been successfully used for the sequential deprotection of diallylamines. The yields of desallylation are good to quantitative.

General synthesis of novel chiral ruthenium catalysts and their use in asymmetric hydrogenation

Abstract The first general synthesis of mononuclear hexacoordinate chiral ruthenium-complexes is presented. Four chiral ruthenium(II)(2-methylallyl) 2 complexes containing Diop, Chiraphos, Norphos, and Binap were prepared in 50–71% yield under mild conditions, and were found to be effective for asymmetric hydrogenation of unsaturated carboxylic acids to give the corresponding saturated derivatives attaining 90% optical purity.

Enantioselective hydrogenation of β-keto sulfones with chiral Ru(II)-catalysts: synthesis of enantiomerically pure butenolides and γ-butyrolactones

Abstract A series of β-hydroxy sulfones were synthesized with high enantioselectivities via a new enantioselective ruthenium-catalyzed hydrogenation using MeO-BIPHEP as a ligand. Some β-hydroxy sulfones were used in the synthesis of optically active butenolides and γ-butyrolactones with high yields and enantioselectivities over 95%.

Regio-and stereoselective palladium catalyzed amination of allylic substrates. Synthesis of E-4-amino-2-alken-1-ol derivatives

Abstract Under mild conditions 4 , 5 and 6 react with primary and secondary amines in the presence of palladium phosphine complexes as catalysts to give 4-amino-2-alken-1-ols with (E) stereochemistry.