Reactions of lithium enolate 2, generated from (5S)-5-(l-menthyloxy)-4-(pyrrolidin-l-yl)furan-2(5H)-one (la) or from the mixture of epimers at C-5 (la, lb), with different sort of electrophiles, such as alkylating agents, aldehydes, acyl chlorides, dimethyl carbonate and a Michael acceptor, occur regioselectively and stereoselectively from the Re face of the enolate to give the corresponding 5-substituted derivatives in synthetically useful yields. The stereoselectivity of the reactions is influenced by the nature and steric bulk of the substituents on the reactive center of the electrophile.
Considerable effort has been made in the development of generally applicable synthetic routes for the construction of functionalized furan-2(5H)-ones, due to their versatility as intermediates in organic synthesis. A convenient approach to the title compounds could be the reaction with electrophiles of the enolate anions generated from simple furanone derivatives, since in the literature it has been reported that the presence of an electron-releasing group, as alkoxy ~3 or alkylamino, 49 at the 4-position favours the formation of the C-5 substituted derivatives. Thus, we have previously reported that 5-methoxy-4-(pyrrolidin-l-yl)furan-2(5H)-one is readily deprotoned by lithium diisopropylamide (LDA) to its anion and this species, although it could act as tridentate anion (scheme 1), reacts with different types of
° r l
~N~H t 0 LDA 0 > 0 0
Scheme 1 electrophiles exclusively at the C-5 position. 7 However, there are few reports dealing with the stereoselective introduction of the substituents at C-5 of vinylogous urethane furanones by the above methodology. ~' 6' 8"9 All reported cases refer to reactions of enolates, in which the chiral auxiliary group is