Further Uses of Pyrrole-Based Dienoxysilane Synthons: A Full Aldol Approach to Azabicyclo[x.2.1]alkane Systems.

Two racemic 2-azabicyclo[2.2.1]heptane structures, 15 and
21, and two chiral non-racemic 6-azabicyclo[3.2.1]octane
representatives, 28 and 36, have been synthesized starting
from 1-(tert-butoxycarbonyl)-2-(tert-butyldimethylsilyloxy)-
pyrrole (TBSOP, 5) and suitable ketones, 9, 16, 22 and 29. 2-
Azabicycle 15 was then elaborated to racemic cyclopentane
amino acid 38, while 6-azabicycle 36 served to access the
enantiomerically pure normorphan-type structure 40. For all
substrates, a uniform synthetic scheme was implemented
based on the combination of two diastereoselective aldoltype
carbon-carbon bond-forming reactions, the efficiencies of which were secured by appropriate aldol-stabilizing steps.
A mechanistic rationale accounting for the markedly diastereoselective
character of the key Mukaiyama aldol reactions
between TBSOP and the ketone acceptors has been
postulated that involves hetero-Diels-Alder transition-state
structures in which the preference for endo versus exo addition
is governed by the electronic nature of the substituents
in the ketone substrates.