Stereoselective solvent induced 1,3-proton transfer of an allylic alkoxide to a homoallylic alkoxide catalysed by a chiral lithium amide

Abstract

Stereoselective rearrangements of e.g.meso-epoxides by chiral lithium amides yield chiral allylic alcohols in high enantiomeric excess. Such products are useful synthetic intermediates. Lithium (S)-2-(pyrrolidin-1-ylmethyl)pyrrolidide Li-2 has been found to deprotonate cyclohexene oxide 1 in tetrahydrofuran (THF) to yield the allylic lithium alkoxide of (S)-cyclohex-2-en-1-ol (S)-Li-3 in 80% ee. Upon changing solvent from THF to 2,5-dimethyltetrahydrofuran (2,5-DMTHF) a 1,3-proton transfer of (S)-Li-3 is induced yielding the lithium alkoxide of (S)-cyclohex-3-en-1-ol (S)-Li-4. Thus the reaction gives access to the homoallylic alcohol 4. This rearrangement has previously been shown to take place with retention of the stereocenter and intramolecularly. We here report further results on the stereochemistry of this isomerisation. For this purpose a synthesis of the deuterium labelled compound, (S)-2-deuterio-3-methylcyclohex-2-en-1-ol (S)-²H-5, has been developed. Solvent induced isomerisation of the lithium alkoxide of (S)-²H-5 in 2,5-DMTHF gave after isolation only the rearrangement product (1S,2R)-2-deuterio-3-methylcyclohex-3-en-1-ol (1S,2R)-²H-6 as shown by NMR and computational modelling. No trace of the isotopomer and diastereoisomer (1S,2S)-²H-6 could be detected. Thus it is concluded that the rearrangement stereoselectively protonates the C-2 carbon anti to the alkoxide oxygen to yield the product. Further details of the reaction mechanism are currently under investigation.