Rearrangement of β‐amino alcohols and application to the synthesis of biologically active compounds

Abstract

Beta-amino alcohols derived from natural amino acids have been used extensively as a powerful source of chirality. Transformation of the hydroxy group of these beta-amino alcohols into a good leaving group, by using trifluoroacetic anhydride, led to rearranged beta-amino alcohols in good yields and with high enantiomeric excesses. This rearrangement has allowed the transformation of substituted prolinols to substituted 3-hydroxypiperidines and linear beta-amino alcohols, issued from natural amino acids, to rearranged beta-amino alcohols.

Synthesis of 2‐Fluoroalkyl 4‐Substituted Azepanes

“…Having pyrrolidines (±)‐ 6 and (±)‐ 7 in hand, these latter were treated under the previously tuned up conditions allowing the ring expansion of pyrrolidines to piperidines,[17c] e.g. with Tf 2 O (1.1 equiv.)…”

“…In the context of our ring‐expansion program, we would like to report the synthesis of optically active α‐trifluoromethyl‐, α‐difluoromethyl‐ and α‐perfluoroalkyl‐substituted azepanes A , which were envisaged by regioselective ring‐opening of an azetidinium intermediates of type B issued from pyrrolidines C . These latter would be synthesized from l ‐proline (Scheme ).…”

Catalytic Formation of Silicon–Heteroatom (N, P, O, S) Bonds

“…have expanded the application of B(C 6 F 5 ) 3 to the double hydrosilylation/reduction of conjugated nitriles . This is a very interesting route, because it allows β‐silylamines to be obtained, and they can subsequently be converted into β‐amino alcohols (Scheme ), which are very interesting molecules owing to their biological and chemical activity …”

Synthesis of Substituted α-Trifluoromethyl Piperidinic Derivatives

“…The ring expansion of pyrrolidines to piperidines via an aziridinium intermediate under kinetic and thermodynamic conditions is well-established [23,24,25,26,27,28]. This method was used to access piperidines 30 , 30′ from prolinols 29 , 29′ .…”