A catalytic amount of KF.18-crown-6 complex is effective as a soluble fluoride source to activate an asymmetric Sakurai-Hosomi allylation with BINAP and silver(I) triflate catalyst. The allylation of a variety of aromatic, alpha,beta-unsaturated and aliphatic aldehydes with allylic trimethoxysilane resulted in high yields and remarkable enantioselectivities. In addition, the asymmetric Mukaiyama-type aldol reaction is achieved by using trimethoxysilyl enol ethers in the presence of the same catalysts. High anti selectivity is obtained from E-silyl enol ether, while Z-silyl enol ether gives syn selectivity.

BINAP/AgOTf/KF/18-crown-6 as new bifunctional catalysts for asymmetric Sakurai-Hosomi allylation and Mukaiyama aldol reaction.

Recent developments in asymmetric aldol methodology

Catalytic asymmetric Mukaiyama-type aldol reaction using trimethoxysilyl enol ethers was achieved using 2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl (p-Tol-BINAP)·AgF complex as a catalyst. The chiral silver(I) catalyst was easily generated by mixing p-Tol-BINAP and silver(I) fluoride in MeOH at room temperature. High syn- and enantioselectivities were obtained from both the E- and Z-silyl enol ethers. Use of a 1 : 1 mixture of MeOH and acetone as a solvent in the reaction of cyclohexanone-derived trimethoxysilyl enol ethers resulted in higher enantioselectivity.

Catalytic Asymmetric Aldol Reaction of Trimethoxysilyl Enol Ethers Using 2,2′-Bis(di-p-tolylphosphino)-1,1′-binaphthyl·AgF Complex

Facile inversion of configuration of N-Boc-β-aminoalcohols via SN2 cyclization to oxazolidinones

In the presence of equimolar amounts of lithium alkoxides derived from N -substituted 2-amino-1,2-diphenyl-ethanols, alkyllithium reagents add to benzaldehyde to furnish optically active secondary alcohols with enantiomeric excesses of up to 86%. The best results were obtained using the N -isopropyl- N -methyl substituted amino-alcohol.

New 1-amino-1,2-diphenylethanols as ligands for the enantioselective addition of alkyllithiums to benzaldehyde

Reaction conditions for the enantioselective aldol reaction of 2, 2-dimethyl-3-pentanone (3) and benzaldehyde using the chiral lithium amide 1b as a chiral auxiliary were thoroughly investigated. All three procedures, that is, (1) the combined use of lithium diisopropylamide and the chiral lithium amide 1b, (2) the use of an excess of the chiral lithium amide 1b, and (3) the regeneration of the chiral lithium amide 1b, afforded the aldol 4 in about 90% yield and 70% enantiomeric excess (ee). Investigation of the effects of solvent by utilizing 1-naphthaldehyde revealed that in tetrahydrofuran, (S, S)-aldol 5 of 77% ee was obtained as the major product, while in ether (R, R)-5 became the major isomer (38% ee). Furthermore, addition of hexamethylphosphoric triamide caused a dramatic change of stereoselectivity, and (S, S)-5 of 70% ee was obtained in ether with 20 eq of hexamethylphosphoric triamid. The aldol 4 of 74% ee was obtained when the new chiral lithium amide 6b was used.

Toshiaki Tatematsu

Papers

Studies on Reaction Conditions and New Entry to Chiral Ligands in the Chiral Lithium Amide-Mediated Enantioselective Aldol Reaction