Palladium-catalyzed asymmetric allylation and complex formation involving P,N-bidentate derivatives of (S)-2-(anilinomethyl)pyrrolidine

P,N-Bidentate (S)-2-(anilinomethyl)pyrrolidine derivatives and their complexes with rhodium(i) and palladium(ii) were synthesized. It was demonstrated that these compounds can be used in the Pd-catalyzed asymmetric allylation for the synthesis of chiral methyl 2-phenyl-2-(2-phenyl-o-carboranyl-1)pent-4-enoate.     

Proline-based P, N ligands in asymmetric allylation and the Heck reaction.

A series of phosphine-oxazoline ligands based on proline are reported. These ligands are synthesized from commercially available trans-4-hydroxy-L-proline in four steps. The ability of this type of ligand to catalyze allylic alkylation in an asymmetric fashion as well as the asymmetric Heck reaction is reported. The best of these ligands gave a palladium complex, which catalyzed the addition of dimethylmalonate to cyclopentenyl acetate in excellent yield and up to 96% ee. This same system catalyzed the Heck reaction between dihydrofuran and cyclohexene in up to 86% ee. These ligands appear to differ from the traditional phosphine-oxazoline ligands in that the stereochemistry of the stereogenic carbon next to the oxazoline is not necessarily the dominant chiral center in the induction of selectivity.     

Synthesis of novel C2-symmetric ligands based on (R,R)- and (S,S)-diphenyl-1,3-propanediol

A range of novel C₂-symmetric dioxygen and dinitrogen ligands can readily be obtained through the interconversion of the parent 1,3-diphenyl-1,3-propanediol enantiomers which are, in turn, accessed in good yields via a Sharpless asymmetric epoxidative resolution.     

Diastereomeric P*-mono- and P*,P*-bidentate diamidophosphite ligands based on 1,4:3,6-dianhydro-d-mannitol in asymmetric metallocomplex catalysis

Synthesis of diastereomeric mono- and bidentate diamidophosphites bearing P*-stereo-centers and phosphabicyclo[3.3.0]octane backbone and their coordination with rhodium(i) and palladium(ii) are considered. Their use in Rh-catalyzed asymmetric allylation allowed one to achieve 87% ee values and the use in Rh-catalyzed asymmetric hydrogenation gave up to 98% ee.     

Preparation of N-phenyl-(S)-prolinol-derived P,N-ligands and their application in Pd-catalyzed asymmetric allylic alkylation

Several NPN-type ligands bearing two chiral pyrrolidinyl groups derived from N-phenyl-(S)-prolinol were prepared by two synthetic methods. Their palladium-complex-catalyzed asymmetric allylic alkylation of malonates with 1,3-diphenyl 2-propenyl acetate delivered the products with good to high enantioselectivities (84–97% ee), including an optically active fluorine-containing compound.     

New ferrocenyl P,S and S,S ligands for asymmetric catalysis

Various new chiral ferrocenyl phosphine-thioethers and thiophosphine-thioethers with planar chirality only have been efficiently synthesized with good overall yields (39–43%) in enantiomerically pure form by a nine-step sequence involving the introduction of the planar chirality by Kagan’s acetal method. These new P,S and S,S ligands have been successfully used in the palladium-catalyzed asymmetric allylic substitution reaction (ee up to 93%).     

Measurement and Identification of (R)- and (S)-6-O-Desmethylnaproxen Enantiomers as Diastereomeric O-Ethoxycarbonyl/(R)-(+)-1-Phenylethylamides in Urine by GC and GC-MS

Enantioseparations of (R)- and (S)-6-O-desmethylnaproxens as O-ethoxycarbonyl/(R)-(+)-1-phenylethylamides and (R)- and (S)-naproxens as (R)-(+)-1-phenylethylamides were achieved by achiral gas chromatography in a single run within 11 min. The characteristic mass spectral patterns facilitated easier peak identification. The method for determinations of (R)-naproxen (1.0 to 50 ng) and (S)-naproxen (100 to 2000 ng) was linear with acceptable repeatability and accuracy. The enantiomeric composition ratios between (R)- and (S)-6-O-desmethylnaproxens and between (R)- and (S)-naproxens in urine sample collected six hours after oral administration of (S)-naproxen tablets were measured to be 2.2 (± 0.2):97.8 (± 0.2) and 2.1 (± 0.1):97.9 (± 0.1), respectively.     

Synthesis of (−)-(5R,6S)-6-acetoxyhexadecanolide based on l-proline-catalyzed asymmetric aldol reactions

A convenient method for proline-catalyzed asymmetric aldol reactions using synthons of straight-chain aliphatic aldehydes, and aldehydes bearing a 1,3-dithiane moiety at the β-position, has been developed. This method was successfully applied to the synthesis of (−)-(5R,6S)-6-acetoxyhexadecanolide, an oviposition attractant pheromone of the female Culex mosquito.     

Pd-Catalyzed asymmetric transformations involving P*-mono- and P*,N-bidentate diamidophosphites derived from (2S,3S)-N 2,3-dimethyl-N 1-phenylpentane-1,2-diamine

The synthesis of new P*-mono- and P*,N-bidentate diamidophosphites, containing 1,3,2-diazaphospholidine rings formed starting from (2S,3S)-N ²,3-dimethyl-N ¹-phenylpentane-1,2-diamine, is described. Comparison of their efficiency in the Pd-catalyzed enantioselective allylation with (E)-1,3-diphenylallyl acetate showed that up to 97% ee was reached in the reaction involving dimethyl malonate as a C-nucleophile. The Pd-catalyzed desymmetrization of N,N′-ditosyl-meso-cyclopent-4-ene-1,3-diol biscarbamate gave up to 61% ee.     

Palladium-catalyzed asymmetric allylic alkylation using (R)-2-(methoxymethyl)pyrrolidine-derived aminophosphine ligands

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 7a using a dimethyl malonate–BSA–LiOAc system has been successfully carried out in the presence of new chiral aminophosphine ligands such as 4 in good yields with good enantioselectivities (up to 96% e.e.).     

Efficient and selective synthesis of (S,R,R,S,R,S)-4,6,8,10,16,18-hexamethyl-docosane via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)

(S,R,R,S,R,S)-4,6,8,10,16,18-Hexamethyldocosane (1) was synthesized in 11% yield in 11 steps in the longest linear sequence from > or =98% pure (S)-beta-citronellal and 6 additional steps for the preparation of 11 in 23% yield from propene. Five of the six asymmetric carbon centers were generated catalytically and stereoselectively by the ZACA reaction (5 times), one lipase-catalyzed acetylation, and two chromatographic operations.     

Efficient asymmetric synthesis of (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine using camphorsultam as a chiral auxiliary

(1R)-(+)-2,10- and (1S)-(-)-2,10-camphorsultam were acylated with ethyl 2-phenylthiazoline 4-carboxylate to afford (+)- and (-)-2-phenylthiazolinylcamphorsultam, which were stereoselectively alkylated with MeI in the presence of n-BuLi. Alkylation of these phenylthiazolinylcamphorsultams occurred from the beta-face rather than alpha-face, resulting in the formation of (S)-alpha-methylcysteine from (1R)-(+)-2,10-camphorsultam and (R)-alpha-methylcysteine from (1S)-(-)-2,10-camphorsultam after acidic hydrolysis. Subsequent protection of the side chain thiol group with trityl alcohol and alpha-amine function with Fmoc-OSu furnished fully protected (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine in overall 20% yield.     

[(1S)-endo]-(−)-borneol-tethered oxazoline phosphite as a P,N-bidentate ligand in palladium-catalyzed enantioselective allylic amination

P,N-Bidentate oxazoline phosphite containing an acyclic phosphorus center with [(1S)-endo]-(−)-borneol fragments and its palladium chelate complex [Pd(η-C₃H₅)(η²-P,N)]BF₄ were synthesized for the first time. The use of this new ligand in Pd-catalyzed asymmetric amination of 1,3-diphenylpropenyl acetate with pyrrolidine afforded the product with 86% ee. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2106–2108, December, 2006.     

First enantioselective total synthesis of (+)-(R)-Pinnatolide using an asymmetric domino allylation reaction

An efficient total synthesis of (+)-(R)-Pinnatolide is described. As a key step an asymmetric multicomponent domino allylation reaction of methyl levulinate is used to form the quaternary stereogenic center in a highly selective way.     

Novel BIPHEN H2 based P,S-bidentate phosphoramidite ligand in palladium-catalyzed asymmetric allylation

The reaction of P,S-phosphoramidite bearing (R_a)-BIPHEN H2 core and exocyclic amino sulfide as the new ligand with [Pd(ppp-allyl)Cl]₂ in the presence of AgBF₄ yielded a cationic metallochelate [Pd(ppp-allyl)(L)]BF₄. This new chiral inducer provided up to 90% ee in the Pd-mediated allylic substitution reaction of (E)-1,3-diphenylallyl acetate with various C- and N-nucleophiles. In the Pd-catalyzed amination of 2-diethoxyphosphoryl-1-phenylallyl acetate with aniline, ee values up to 57% were achieved.     

Pd-Catalyzed asymmetric allylation involving bis(diamidophosphite) based on the salen-type chiral diamine

Russian Chemical Bulletin - New bis(diamidophosphite) ligand with stereogenic phosphorus atoms in the 1,3,2-diaza-phospholidine rings was synthesized based on (1R,2R)-[N,...     

Novel (R)-(+)-limonene-derived ligands: synthesis and application in asymmetric transfer hydrogenations

(R)-(+)-Limonene was transformed into mono-N-tosylated-1,2-diamine derivatives using an N-tosylaziridination procedure followed by sodium azide treatment and reduction on Pd/C. The ligands obtained proved effective in the asymmetric transfer hydrogenation protocol on aromatic ketones.