Synthetic Potential of Regio- and Stereoselective Ring Expansion Reactions of Six-Membered Carbo- and Heterocyclic Ring Systems: A Review

Abstract

Ring expansion reactions fascinate synthetic chemists owing to their importance in synthesizing biologically active compounds and their efficacy in medicinal chemistry. The present review summarizes a number of synthetic methodologies, including stereoselective and regioselective pathways adopted by scientists, for framing medium- to large-size carbo- and heterocycles involving lactams, lactone, azepine and azulene derivatives via ring expansion of six-membered carbo- and heterocycles that have been reported from 2007–2022. Numerous rearrangement and cycloaddition reactions involving Tiffeneau–Demjanov rearrangement, Aza–Claisen rearrangement, Schmidt rearrangement, Beckmann rearrangement, etc., have been described in this regard.

Advances in the synthesis of rearranged homoisoflavonoids

“…96 The researchers obtained this natural product via palladium-catalyzed intramolecular ortho arylation by a Csp 2 –H activation/C–C coupling reaction of biaryls, 97,98 followed by ring-expansion through Tiffeneau–Demjanov rearrangement. 99,100…”

Medium-Sized Ring Expansion Strategies: Enhancing Small-Molecule Library Development

“…Despite significant progress in constructing libraries of small molecules resembling natural products, the synthesis of medium-sized rings, such as those with 8 to 11 members, is notably challenging due to the unique strain and structural constraints they exhibit. One of the primary obstacles in synthesizing these structures is transannular strain, a consequence of the proximity of atoms or functional groups within a ring, which are not directly bonded to each other but are close enough to cause repulsive interactions [35][36][37][38][39][40][41]. This strain crucially influences the conformational stability and preferences of medium-sized rings, affecting their energy and, consequently, their reactivity and chemical behaviors [42].…”