Synthesis of enantiopure cis- and trans-2,3-disubstituted piperidines.

The synthesis of enantiopure cis- and trans-2,3-disubstituted piperidines 4 is described. The key step of the synthesis involves the stereoselective reduction of chiral nonracemic lactams 2 by using BH3.Me2S.

The intriguing reactivity of functionalized beta-amino alcohols with glyoxal: application to a new expedient enantioselective synthesis of trans-6-alkylpipecolic acids.

New beta-amino alcohols possessing a vinylsilane moiety were reacted with glyoxal to produce lactones that were transformed in three steps in enantiopure pipecolic acid derivatives. The key step was a totally diastereoselective ene-iminium cyclization, whose mechanism can be viewed as a direct cyclization of the vinylsilane moiety onto the iminium ion. The reactivity of two beta-amino alcohols having an allylsilane terminator was also examined.

Asymmetric syntheses of new functionalized beta-amino alcohols via diastereoselective addition of organometallic reagents onto oxazolidines.

Diastereoselective reactions between (S)-phenylglycinol-derived oxazolidines and two unsaturated organolithium reagents afforded chiral beta-amino alcohols having vinyl and alkynylsilane moieties. When the same reactions were performed in the presence of titanium isopropoxide, a dramatic change of regioselectivity was observed, from the alpha- to the gamma-position, thus producing beta-amino alcohols with allyl or allenylsilane functions. A rationalization of the observed diastereoselectivity was suggested for each case.

Regio- and Stereocontrolled Formation of Chiral Epoxy Oxazolidines via Bromocarbamation of N-Boc Alkenyl Oxazolidines. Application to Asymmetric Synthesis.

Treatment of alpha-alkenyl N-Boc oxazolidines with N-bromosuccinimide leads to epoxy oxazolidines via a bromocyclocarbamation reaction which is completely stereoselective. Action of sodium azide on these epoxides, followed by a few functional group manipulations, eventually affords chiral beta-amino alcohols which are intermediates for the enantioselective synthesis of bioactive products: the anti side chain of taxol and a hydroxyethylamine isostere. Both the bromocarbamation cyclization and the nucleophilic cleavage of epoxides are totally regioselective.