The diastereoselectivity of electrophilic attack on trigonal carbon adjacent to a stereogenic centre: diastereoselective alkylation and protonation of open-chain enolates having a stereogenic centre at the β position

Abstract

Methylation of the enolates7, 24, 28 and 33 and protonation of the enolates 10, 27, 31 and 36 are diastereoselective in conformity to a general rule, summarised in the drawing 1, governing the stereochemistry of electrophilic attack on a double bond adjacent to a stereogenic centre. The sense of the selectivity is, with one exception, opposite to that of the corresponding nucleophilic attack on a carbonyl group adjacent to a stereogenic centre, which, with the same exception, follows Cram's and the Felkin-Anh rule, summarised in the drawing 2. The exception is probably the reduction 40→38+39, with 39 as the major product. This result is inconsistent with Cram's and the Felkin-Anh rule if the isopropyl group is counted as ‘larger’ than the phenyl group, whereas the Grignard reaction 37→38+39, where 39 is again the major product, and the corresponding electrophilic reactions 33→34+35, with 34 as the major product, and 36→34+35, with 35 as the major product, are all consistent with isopropyl being effectively larger than phenyl.