Sylvain Jugé

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.

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.

Synthesis of α-amino acids. Schiff base of glycine methyl ester. A new and efficient prochiral nucleophile in palladium chiral catalytic allylation

Abstract Asymmetric carbon—carbon bond formation was obtained in optical yields up to 57 %. in allylic alkylations using benzophenone imine of glycine methyl ester 1 as a prochiral nucleophile. Catalytic : (1.5–3 %) palladium—Chiral complexes have been used (12 chiral ligands have been tested) ; (+) or (−) DIOP appeared to be the more efficient. Good chemical yields were also obtained. Catalysis can be performed at low temperature.

Asymmetric synthesis of P-stereogenic o-hydroxyaryl-phosphine (borane) and phosphine-phosphinite ligands

Abstract The first asymmetric synthesis of P-stereogenic 2-hydroxyarylphosphine ligands is described, using borane complexation methodology. This synthesis is based on the highly stereoselective preparation of bromoarylphosphinite boranes, leading to the 2-hydroxyarylphosphine derivatives, by an intramolecular ortho Fries-like rearrangement mediated in basic conditions. The o -anisyl-2-hydroxynaphthylphenylphosphine borane has been decomplexed in EtOH, affording the P(III)-stereogenic hydroxyarylphosphine ligand with 84% yield. The interest of the hydroxyarylphosphine borane is also demonstrated by the preparation of a new class of phosphine-phosphinite ligands, by trapping the rearrangement products first with chlorodiphenylphosphine, Ph 2 PCl, then with borane. The corresponding phosphine-phosphinites are obtained and purified as diborane complexes, with the decomplexation of these borane complexes being achieved by heating with dabco, to afford the free hybrid ligands with retention of the configuration at the P-atom (isolated yield up to 53%).

Applications and stereoselective syntheses of P-chirogenic phosphorus compounds

Phosphorus compounds bearing chirality on the P-center are usually qualified as P-chirogenic or P-stereogenic. This chemical class concerns natural products, agrochemistry, molecular materials, biology and pharmacy, although it is certainly in coordination chemistry and in asymmetric catalysis using chiral transition metal complexes that P-chirogenic phosphorus compounds are the most used. The chiral phosphine ligands and their uses in asymmetric metal-catalyzed reactions have been widely reviewed in literature. However, an overview covering the applications as well as the stereoselective syntheses of all classes of phosphorus compounds has not yet been provided. This review reports the best stereoselective or asymmetric syntheses, the most efficient P*-building blocks and functionalisation of P-chirogenic compounds, in the light of chiral phosphorus compound applications. It is an extensive and useful documentation from pioneering work to recent advances in phosphorus stereochemistry.

Efficient synthesis of quaternary and P-stereogenic phosphonium triflates.

An efficient and general method for the preparation of achiral and chiral phosphonium salts is reported. This synthesis is based on the quaternization of phosphines and their derivatives with arynes generated in situ from 2-(trimethylsilyl)aryl triflates. This methodology is successfully applied to the synthesis of new valuable P-stereogenic phosphonium triflates.

ASYMMETRIC SYNTHESIS OF (S,S)-(+)-1,1'-BIS-(METHYL-PHENYL-PHOSPHINO) FERROCENE

Abstract The asymmetric synthesis of 1,1′-bis-(methyl-phenyl-phosphino) ferrocene 1 is described using the oxazaphospholidine borane complex 5 as synthon. Two strategies were investigated, based either on P C bond formation by ring opening of complex 5 with the 1,1′-dilithio ferrocene 10 , or on homocoupling of the cyclopentadienyl-methyl-phenyl-phosphine borane 2 anion with FeCl 2 . The first leads to a diastereomeric mixture of the diphosphine 1 in a 55:45 ratio, and the low stereoselectivity is explained by the steric hindrance of the ferrocene dianion. In the second strategy, the ( R )-cyclopentadienyl phosphine borane 2 (85% ee ) was prepared by the reaction of CpNa with the optically active chlorophosphine borane 14 , derived from the aminophosphine borane 6a . The coupling of 2 leads to the 1,1′-diphosphino ferrocene borane 13 , which is obtained diastereomerically pure by recrystallization, then decomplexed to the corresponding ( S,S )-diphosphine 1 .

Stereoselective Synthesis of o-Bromo (or Iodo)aryl P-Chirogenic Phosphines Based on Aryne Chemistry

The efficient synthesis of chiral or achiral tertiary phosphines bearing an o-bromo (or iodo)aryl substituent is described. The key step of this synthesis is based on the reaction of a secondary phosphine borane with the 1,2-dibromo (or diiodo)arene, owing to the formation in situ of an aryne species in the presence of n-butyllithium. When P-chirogenic secondary phosphine boranes were used, the corresponding o-halogeno-arylphosphine boranes were obtained without racemization in moderate to good yields and with ee up to 99%. The stereochemistry of the reaction, with complete retention of the configuration at the P atom, has been established by X-ray structures of P-chirogenic o-halogenophenyl phosphine borane complexes. The decomplexation of the borane was easily achieved without racemization using DABCO to obtain the free o-halogeno-arylphosphines in high yields.

Versatile synthesis of P-chiral (ephedrine) AMPP ligands via their borane complexes. Structural consequences in Rh-catalyzed hydrogenation of methyl α-acetamidocinnamate

Abstract An efficient and versatile synthesis of aminophosphine phosphinite (AMPP) ligands derived from ephedrine, with possible stereogenic P(III)-center(s) is described, using the borane complex methodology. The reaction of oxazaphospholidine borane with an organolithium reagent, leads to the formation of the ring-opened product, which is trapped by a chlorophosphine (borane), to afford the corresponding aminophosphine phosphinite boranes in good yields. Treatment of the borane complexes with dabco, gives the corresponding aminophosphine phosphinite ligands in 70–90% yield. These ligands are used for the preparation of Rh catalysts applied to the asymmetric hydrogenation of methyl α-acetamidocinnamate yielding the phenylalanine derivative with ( R ) 22% to ( S ) 99% e.e. These results show the importance of the structural modification at the P-stereogenic center(s), which could either amplify or cancel out the asymmetric induction resulting from the ephedrine backbone, for enantioselective catalysis.

Chemo-, regio- and stereoselective conversion of P-chirogenic phosphorus borane complexes into their PO or PS derivatives

Abstract Chiral and achiral organophosphorus borane complexes are readily transformed into their corresponding phosphoryl or thiophosphoryl compounds in high yields using one-pot procedures with stereoselectivities reaching 100% in many cases. Both oxidation and sulfuration were performed under neutral or mild conditions and were applied to various organophosphorus borane complexes (phosphines, phosphinates, chlorophosphines, aminophosphines, etc.). In the case of the dissymmetric diphosphine or aminophosphine phosphinite ligands, the reaction of their diborane complexes proceeds regiospecifically to a single phosphorus group, affording the corresponding hybrid derivatives.