Stereoselective Synthesis of Polysubstituted Spiropentanes

Abstract

A new approach to polysubstituted spiropentanes is developed through a regio-and diastereoselective carbometalation of sp 2 -disubstituted cyclopropenes. The control of selectivity originates from a combined syn-facial diastereoselective carbometalation with a regio-directed addition. The regio-controlling element subsequently serves as a leaving group in an intramolecular nucleophilic substitution. This method allows the preparation of various polysubstituted spiropentanes with up to five contiguous stereocenters.

Synthesis of Stereodefined Polysubstituted Bicyclo[1.1.0]butanes

“…Our group has recently reported an efficient and straightforward synthesis of stereodefined polysubstitued spiropentanes 3. 65 The method involves a diastereoselective carbocupration reaction of cyclopropenes cyclopropyl copper species 2, which subsequently cyclize to produce the expected spiropentanes 3 (Scheme 2a) with excellent diastereoselectivity. Motivated by the success of this approach, we set out to utilize the cyclization of cyclopropyl metal species to stereoselectively produce BCBs (Scheme 2b).…”

“…Our group has recently reported an efficient and straightforward synthesis of stereodefined polysubstitued spiropentanes 3 . The method involves a diastereoselective carbocupration reaction of cyclopropenes 1 to generate cyclopropyl copper species 2 , which subsequently cyclize to produce the expected spiropentanes 3 (Scheme a) with excellent diastereoselectivity.…”

Diastereoselective Hydroacylation of Cyclopropenes by Visible-Light Photocatalysis

“…Considering the efficiency and atom economy, ring-retentive functionalization of cyclopropene is the most attractive alternative for forming polysubstituted cyclopropanes . The Marek and Fox groups have made tremendous efforts in this field after Nakamura’s pioneering work for Fe-catalyzed carbometalation of cyclopropene . Different methods have been published on transition metal (Pd, Rh, Cu, Co, etc.)…”

Directed Diastereoselective Cyclopropanation and Epoxidation of Alkenyl Cyclopropyl Carbinol Derivatives

“…During our studies on the diastereoselective synthesis of polysubstituted cyclopropanes − as a new source of stereodefined acyclic products, we have recently shown that alkenyl cyclopropyl carbinol derivatives 1 exhibit an excellent directing effect for the palladium-catalyzed tandem Heck addition and ring opening reaction − as well as for diboration reactions (Scheme a). Even more distant alkenyl biscyclopropyl carbinol 2 led to a completely diastereoselective Heck addition reaction before the subsequent selective double ring-opening.…”