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 alpha-alkoxycarbenium ion and an axially positioned oxygen substituent are believed to play a significant role in organizing the transition structure of the Prins cyclization.