Enamine chemistry. Part 29. Synthesis of adamantane derivatives from α,β-unsaturated acid chlorides and 4,4-disubstituted cyclohexanone enamines. Multiple [3,3] sigmatropic rearrangement transition state stereochemistry. X-Ray analysis

Abstract

Chemical, spectroscopic and X-ray crystallographic evidence has confirmed that the three isomers of 6-hydroxy-7,9-dimethyl-6-phenyladamantane-2,4-dione, obtained by the reaction of crotonoyl chloride with the pyrrolidine enamine of 4-benzoyl-4-methylcyclohexanone, have the 9α-methyl-6α-phenyl (4), 9β-methyl-6α-phenyl (2), and 9β-methyl-6β-phenyl (3) configurations. The mechanism of their formation has been investigated and the evidence available indicates that the stereochemistry of the C-6 and C-9 chiral centres is determined largely by the stereochemistry of the [3,3] sigmatropic rearrangement leading to them. A chair-like transition state for the rearrangement, occurring from the same side of the cyclohexene ring as the benzoyl group (chair-syn) in the intermediate N-acylated enamine (9a) must lead to the 9α-Me,6α-Ph configuration as in (4), whereas the same process from the opposite side (chair-anti) followed by inversion of the substituted ring carbon could lead to the 9β-Me,6β-Ph configuration as in (2) and the 9β-Me,6α-Ph configuration as in (3). However, the main isomer (3), having the more crowded 9β-Me,6β-Ph configuration, is more likely to be derived by a [3,3] sigmatropic rearrangement having a boat-like transition state, but again occurring from the same side of the cyclohexene ring as the benzoyl group (boat-syn). An X-ray crystallographic analysis of 6β- hydroxy-7,9α-dimethyl-6α-phenyladamantane-2,4-dione (4) and of 3-(5-benzoyl-5-methyl-2-oxocyclohexyl)-butanoic acid (34), isolated at an intermediate stage in the above reaction, has been carried out. The corresponding reaction of αβ-unsaturated acid chlorides with enamines of 4-benzoyl-4-phenyl-cyclohexanone (9c) and ethyl 1 -benzoyl-4-oxocyclohexane-1 -carboxylate (9b) has been carried out and shown to lead to 6-hydroxy-6,7-diphenyladamantane-2,4-diones and ethyl 2-hydroxy-4,6-dioxo-2-phenyladamantane-1 -carboxylates respectively, as a mixture of stereoisomers. A similar multiplicity in the stereochemistry of the transition state of the [3,3] sigmatropic rearrangement is evident from the structures of the adamantane derivatives produced.