Scope and Facial Selectivity of the Prins-Pinacol Synthesis of Attached Rings

Using a B-alkyl Suzuki cross-coupling as a key step, a concise and stereocontrolled synthesis of five- to
eight-membered triisopropylsiloxy ethers having (2Z)-(6,6-dimethoxyhexylidene) or (2Z)-(5,5-dimethoxypentylidene) side chains was developed. Prins-pinacol reactions of these precursors promoted by SnCl4
provide bicyclic products in which 5-, 6-, or 7-membered rings are joined by a C−C single bond.
Synthetically challenging attached ring systems in which both rings are chiral can be prepared in this
fashion with high stereo- and enantioselectivity. Stabilizing through-space electrostatic interactions between
the α-alkoxycarbenium ion and an axially positioned oxygen substituent are believed to play a significant
role in organizing the transition structure of the Prins cyclization.