Nucleophilic Transformations of Lewis Acid-Activated Disubstituted Epoxides with Catalyst-Controlled Regioselectivity

Abstract

Due to their inherent ring strain and electrophilicity, epoxides are highly attractive building blocks for fundamental organic reactions. However, controlling the regioselectivity of disubstituted epoxide transformations is often particularly challenging. Most Lewis acid-mediated processes take advantage of intrinsic steric or electronic substrate bias to influence the site of nucleophilic attack. Therefore, the scope of many of these systems is frequently quite limited. Recent efforts to generate catalysts that can overcome substrate bias have expanded the synthetic utility of these well-known reactions. In this Perspective, we highlight various regioselective transformations of disubstituted epoxides, emphasizing those that have inspired the production of challenging, catalyst-controlled processes.

Catalyst-Free Synthesis of Benzofuran Derivatives from Cascade Reactions between Nitroepoxides and Salicylaldehydes

“…α-Nitroepoxides could be rearranged to α-nitroketones and α-hydroxy ketones or reduced to β-nitrobenzylamine derivatives as the precursors for pseudoephedrines . Moreover, several useful syntheses could be started from β-nitrostyrenes to produce structures of interest. − …”

Self-Assembled Bimetallic Aluminum-Salen Catalyst for the Cyclic Carbonates Synthesis

“…Those catalysts can self-assemble in solution through weak hydrogen bonding interactions [ 31 , 35 ]. Herein, we report that the self-assembling bimetallic strategy can also be applied to the salen-aluminum catalysts for the cyclic carbonate synthesis from CO 2 and epoxides [ 36 , 37 , 38 , 39 , 40 , 41 ].…”

Catalyst-Controlled Regioselective Carbonylation of Isobutylene Oxide to Pivalolactone

“…Ring-expansion carbonylation of 2,2-disubstituted epoxides is well-known, and several generations of catalysts have been identified . Drent and co-workers developed the first carbonylation of isobutylene oxide in 1994 using a Co 2 (CO) 8 /3-hydroxypyridine catalyst .…”

“…Ring-expansion carbonylation of 2,2-disubstituted epoxides is well-known, 12 and several generations of catalysts have been identified. 13 Drent and co-workers developed the first carbonylation of isobutylene oxide in 1994 using a Co 2 (CO) 8 /3-hydroxypyridine catalyst. 14 However, this system selectively inserted CO at the less-substituted position to form the β,β-disubstituted steric lactone (3) and produced various side products.…”