Stereochemical investigation on the construction of poly-functionalized bicyclo[3.3.1]nonenones by successive Michael reactions of 2-cyclohexenones?

Organic & Biomolecular Chemistry Pub Date: 2006-12-08 DOI: 10.1039/B615702E

Abstract

A method for the practical construction of poly-functionalized bicyclo[3.3.1]nonenones by successive Michael reactions of cyclohexenones 1 with acrylates 2 using K2CO3 and TBAB (n-Bu4N+Br?) was developed. The construction could be carried out in both stepwise and one-pot reactions with similar tendencies in regioselectivity. The α-regioselectivity in the intramolecular Michael reaction agreed with that stereoelectronically expected in intermolecular reactions based upon consideration of the HOMO orbital profile of the enolate I, the precursor to ring-closure, although the reaction site was trisubstituted and prone to steric hindrance in most of the examples presented. For the acetoxymethylacrylates substituted at either the α or γ position, steric hindrance of the substituents (R2 and R3) served as a controlling factor to induce high regiocontrol. Facial selection in the protonation of enolate II, formed upon ring-closure, was also affected by these substituents. In both the intramolecular Michael reaction and the protonation of enolate II, the ammonium counter cation played an important role.

Graphical abstract: Stereochemical investigation on the construction of poly-functionalized bicyclo[3.3.1]nonenones by successive Michael reactions of 2-cyclohexenones
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