Synthetic Applications and Methodological Developments of Donor−Acceptor Cyclopropanes and Related Compounds

Abstract

Donor–acceptor cyclopropanes are convenient precursors to reactive and versatile 1,3-dipoles, and have found application in the synthesis of a variety of carbo- and heterocyclic scaffolds. This perspective review details our laboratory’s use of donor–acceptor cyclopropanes as intermediates toward the total synthesis of various natural products. We also discuss our work in the development of novel cycloadditions and rearrangements of donor–acceptor cyclopropanes and aziridines, as well as an example of an aryne insertion proceeding via fragmentation of a transient donor–acceptor cyclobutane.

Catalytic Enantioselective Ring-Opening Reactions of Cyclopropanes

“…Due to the presence of a highly polarized bond, the catalytic activation of D–A cyclopropanes is easy and has been extensively investigated. − Ring opening is usually triggered by a LUMO-lowering Lewis acid catalyst through coordination of the electron-withdrawing substituent, very often via chelation to a diester, facilitating the attack by a nucleophile. In contrast, the HOMO-raising approach (activation of the electron-donating group) is less frequent and has been mostly achieved via enamine/enolate formation or Umpolung of carbonyls with a carbene catalyst.…”

“…Upon activation, a formal 1,3-zwitterion is formed and can react with a nucleophile, an electrophile, or a multiple bond system, leading to acyclic or cyclic products. This exceptional reactivity has been widely used in synthetic chemistry and has been covered by numerous reviews, − with only one dedicated to enantioselective transformations . The most frequently used acceptor is by far a diester group, although ketones, nitriles, and nitro groups have been used in some instances.…”

Donor‐Acceptor Cyclopropanes in the Synthesis of Carbocycles

“…These substrates have been also found to react as synthetic equivalents of alkylidene malonates . Based on these advances, total syntheses of diverse natural products from D‐A cyclopropanes have been developed . With all these achievements in mind, Werz and co‐authors have characterized this period as “A new golden age for donor‐acceptor cyclopropanes” .…”

Formal Insertion of Thioketenes into Donor–Acceptor Cyclopropanes by Lewis Acid Catalysis

“…In the recent past, donor–acceptor (D–A) cyclopropanes have become a center of attention in organic synthesis as valuable three-membered building blocks. Even though the pioneering work by Wenkert and Reissig took place in the 1970s and 1980s, only in the past decade have they been extensively utilized by many groups to access complex carbo- and heterocyclic scaffolds and have even been employed in natural product synthesis . The vicinal arrangement of donor and acceptor substituents in combination with a high ring strain of ∼115 kJ/mol explains why they commonly react with 1,3-zwitterionic character, and this special behavior paves the way for numerous transformations.…”