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

摘要

Stereoselective rearrangements of e.g. meso-epoxides by chiral lithium amides yield chiral allylic alcohols in highnenantiomeric excess. Such products are useful synthetic intermediates. Lithium (S)-2-(pyrrolidin-1-ylmethyl)-npyrrolidide Li-2 has been found to deprotonate cyclohexene oxide 1 in tetrahydrofuran (THF) to yield thenallylic lithium alkoxide of (S)-cyclohex-2-en-1-ol (S)-Li-3 in 80% ee. Upon changing solvent from THF ton2,5-dimethyltetrahydrofuran (2,5-DMTHF) a 1,3-proton transfer of (S)-Li-3 is induced yielding the lithiumnalkoxide of (S)-cyclohex-3-en-1-ol (S)-Li-4. Thus the reaction gives access to the homoallylic alcohol 4. Thisnrearrangement has previously been shown to take place with retention of the stereocenter and intramolecularly.nWe here report further results on the stereochemistry of this isomerisation. For this purpose a synthesis ofnthe deuterium labelled compound, (S)-2-deuterio-3-methylcyclohex-2-en-1-ol (S)-n2nH-5, has been developed.nSolvent induced isomerisation of the lithium alkoxide of (S)-n2nH-5 in 2,5-DMTHF gave after isolation only thenrearrangement product (1S,2R)-2-deuterio-3-methylcyclohex-3-en-1-ol (1S,2R)-n2nH-6 as shown by NMR andncomputational modelling. No trace of the isotopomer and diastereoisomer (1S,2S)-n2nH-6 could be detected.nThus it is concluded that the rearrangement stereoselectively protonates the C-2 carbon anti to the alkoxidenoxygen to yield the product. Further details of the reaction mechanism are currently under investigation.