The stereocontrolled synthesis of trisubstituted and tetrasubstituted tetrahydrofurans:

In the early 1980's, our laboratories investigated new methods for the stereoselective preparation of highly substituted tetrahydrofurans. One study utilized stereoselective condensations of α-lithiosulfinyl carbanions with aldehydes. As illustrated by the example below, cyclization of the chiral sulfoxide (1) takes place via in situ reduction to the sulfide (2). Sulfides(2) were independently prepared by borane reducation and subsequent treatment of (2) with dimethylsulfate led to neighboring group participation by sulfur for internal backside displacement. The episulfonium intermediate (3) is captured by the proximate oxygen for 5-membered ring closure and O-dealkylation to give (4). Overall ring formation features dehydration with retention of stereochemistry as a highly innovative approach to THF formation.

Primary references: J. Am. Chem. Soc. 1981, 103, 7398, Tetrahedron 1986, 42, 3003, Tetrahedron 1986, 42, 3013.