Regioselective and stereoselective cleavage of cis‐4‐methyl‐2‐vinyl‐l,3‐dioxane by alkyllithiums

Abstract

The reaction of alkyllithiums with cis-4-methyl-2-vinyl-1,3-dioxane proceeds in virtually quantitative yield via a formal S(N)2' ring opening that proceeds in a regioselective manner to give preferential cleavage of the C(2)-O(l) bond remote from the 4-methyl substituent, affording the E-enol ether as the major stereoisomer. A two-step mechanism, involving addition of the alkyllithium followed by syn-elimination of lithium alkoxide, is suggested to account for the stereochemical outcome.

Stereoselectivity of Intramolecular SN‘ Cyclizations of Alkyllithium Reagents on Methoxy Alkenes

“…Organolithium reagents derived from cyano acetals 38 and 39 cyclize onto secondary methoxy alkenes in an S N ‘ fashion and generate novel spiro compounds with two new stereogenic centers. The methyl ether is a robust functional group that can be installed at an early stage of a synthetic sequence 9a. Primary allyl methyl ethers are more reactive than simple alkenes in the reductive cyclization reactions.…”

“…The dominant effect in these α-alkoxy alkyllithium cyclizations is the spiroether preference for an alkene cis to the ring oxygen (e.g., structure 7 , Scheme ). The preference for the syn-S N ‘ cyclization (e.g., structure 2 , Scheme ) is secondary, followed by the preference for E -alkene formation previously identified by Stille …”

“…Intermolecular S N 2‘ reactions have been investigated and in some cases found to prefer syn-S N 2‘ substitution, but the substrates are sterically biased and the conclusions may not be general . Conversely, Stille showed that S N ‘ cyclization preferentially generates E -alkenes with 10:1 to 20:1 selectivity, but he assumed in his work that anti-S N ‘ cyclization of an organolithium species was favored by analogy to cuprate additions .…”