Ping Yu Wu

Asymmetric Addition of Dimethylzinc to α-Ketoesters Catalyzed by (−)-MITH

This investigation describes the catalytic asymmetric addition of dimethylzinc to alpha-ketoesters in the presence of (-)-MITH ( 5) and triethyl borate as an additive to give the corresponding chiral alpha-hydroxy esters with good yields and high enantioselectivities.

Highly enantioselective Rh-catalyzed alkenylation of imines: synthesis of chiral allylic amines via asymmetric addition of potassium alkenyltrifluoroborates to N-tosyl imines.

For the first time, simple N-tosyl aryl aldimines, prepared from the condensation of tosyl amide and aromatic aldehydes, can be used as substrates in the rhodium catalyzed 1,2-addition reaction using alkenylboron nucleophiles. In the presence of 1.5 mol % of [RhCl(1e)]2, enantioselective addition of various potassium alkenyltrifluoroborates to aryl aldimines furnished the corresponding chiral allylic amines in 73-96% yield and 72->99.5% ee. Notably, this method efficiently provides the di-, tri-, and tetrasubstituted allylic N-tosyl amines with high asymmetric induction.

Rhodium-Catalyzed Asymmetric Addition of Arylboronic Acids to β-Nitroolefins: Formal Synthesis of (S)-SKF 38393

An efficient enantioselective addition of an array of arylboronic acids to various β-nitrostyrenes catalyzed by a novel and reactive rhodium-diene catalyst (S/C up to 1000) was developed, providing β,β-diarylnitroethanes in good to high yields (62-99%) with excellent enantioselectivities (85-97% ee). The method was extended to 2-heteroarylnitroolefins and 2-alkylnitroolefins similarly providing the desired products with high enantioselectivities and yields. The usefulness of this method was demonstrated in the formal synthesis of the enantiomer of the dopamine receptor agonist and antagonist, SKF 38393.

Enantioselective and Rapid Rh-Catalyzed Arylation of N-Tosyl- and N-Nosylaldimines in Methanol

Enantiomerically enriched tosyl-protected diarylmethylamines were rapidly prepared by the asymmetric addition of arylboronic acids to N-tosylaldimines under mild conditions in the presence of a catalyst prepared in situ from Rh(I) and a chiral diene ligand. This methodology offers access to diarylmethylamines in good yields with excellent chiral purity at room temperature using MeOH as a solvent and NEt3 as a base. Its synthetic utility was demonstrated by the preparation of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (14), an antagonist of the N-methyl-d-aspartate (NMDA) receptor.

Enantioselective addition of dialkylzincs to aldehydes catalyzed by (-)-MITH.

An effective catalytic system that imparts high enantioselectivity has been disclosed for the synthesis of optically active alcohols, which may undergo further chemical transformations. The enantioselective alkylation of aldehydes with dialkylzincs to afford the corresponding optically active alcohols with excellent enantioselectvities has been achieved in the presence of 0.1-0.5u2005molu2009% of the camphor-derived chiral ligand (-)-2-exo-morpholinoisobornane-10-thiol (MITH) (1) at room temperature or at 0u2009°C.

Rhodium/Chiral Diene Complexes in the Catalytic Asymmetric Arylation of β-Pyrazol-1-yl Acrylates

The asymmetric conjugate addition of arylboronic acids to substituted and unsubstituted β-pyrazol-1-yl (E)-tert-butyl acrylates 4 catalyzed by 5 mol % of the Rh(I)/diene 2a catalyst provided the corresponding addition products in 44-98% yield and 91->99.5% ee. The method was applied to the formal synthesis of (3S)-3-aryl-3-(pyrazol-1-yl)propanoic acid 1b with agonistic activity toward the human GPR40 G-protein coupled receptor.

Direct synthesis of chiral 3-arylsuccinimides by rhodium-catalyzed enantioselective conjugate addition of arylboronic acids to maleimides.

Chiral rhodium catalysts comprising 2,5-diaryl- substituted bicyclo[2.2.1]diene ligands L1-L10 were utilized in the enantioselective 1,4-addition reaction of arylboronic acids to N-substituted maleimides. In the presence of 2.5u2005molu2009% of Rh(I) /L2, enantioenriched conjugate addition adducts were isolated in 72-99u2009% yields with 86-98u2009%u2005ee. This protocol offers a convenient method to access a variety of 3-arylsuccinimides in a highly enantioselective manner. Maleimides with readily cleavable N-protecting groups were tolerated enabling the synthesis of useful synthetic intermediates. Pyrrolidine 4, a biologically active compound, and pyrrolidine 5, an ent-precursor to an HSD-1 inhibitor, were synthesized to demonstrate the utility of this method.

Design and Synthesis of Chiral Diene Ligands for RhI-Catalyzed Enantioselective Arylation of N-DPP-protected Aldimines: Synthesis of the Antifungal Agent Bifonazole

Herein we describe the design and synthesis of a novel family of bifunctional, chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups, and demonstrate their usefulness in the RhI -catalyzed enantioselective addition reaction of arylboronic acids to N-diphenylphosphinyl (N-DPP)-protected aldimines. Unlike the analogous RhI -catalysts comprising diene ligands substituted with aryl and carboxylic ester groups, or only with aryl groups, the addition reaction proceeded with high stereoselectivity. The protocol tolerated a range of N-DPP-aldimines and arylboronic acids, producing the desired optically active N-DPP-protected amines with yields between 31-99u2009% and with ee values up to 91-99u2009%. The synthetic utility of the method was demonstrated by the conversion of N-DPP-protected amine 3u2009ae into the antifungal agent, bifonazole (13).

Rh-Catalyzed Enantioselective Allylation of N-Tosyl- and N-Nosylaldimines: Total Synthesis of (−)-Crispine A

The unprecedented development of asymmetric Rh-catalyzed 1,2-allylation of N-Ts- and N-Ns-aldimines is achieved. This protocol utilizes potassium allyltrifluoroborates and various aldimines to generate enantioenriched homoallylic amines in the presence of 3.0 mol % of Rh(I)/L1b catalyst with up to 90% yield, 98% ee (R = H), and 10:1 diastereoselectivity (R = Me or Ph), yielding the same major diastereomer when using potassium (E)- and (Z)-crotyltrifluoroborate. Its synthetic utility is also illustrated in the total synthesis of (-)-crispine A.