Domino‐Ring Opening‐Cyclization (DROC) of Donor‐Acceptor (DA) Cyclopropanes

Abstract

A new concept called “domino‐ring opening‐cyclization (DROC)” has been introduced by us where both the reactive centres of the DA cyclopropane participate in the bond formation, with a suitable reagent bearing both nucleophilic and electrophilic terminals in a domino fashion. The present review is intended to concisely describe the evolution of this new concept.

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.…”

Reactions of Styrylmalonates with Aromatic Aldehydes: Detailed Synthetic and Mechanistic Studies

“…In recent decades, donor–acceptor cyclopropanes (DACs) have become quite popular in organic synthesis as versatile building blocks for constructing various structures, from aliphatic ones to polycyclic ones. − This is confirmed by the ever increasing number of publications on their chemistry in highly ranked journals. − 2-Arylcyclopropane-1,1-dicarboxylates (ACDCs) are the most frequently used and versatile representatives of DACs. Although a wide variety of chemical processes involving DACs have been developed, the majority of their reactions can be attributed to two main types of reactivities.…”

“…Although a wide variety of chemical processes involving DACs have been developed, the majority of their reactions can be attributed to two main types of reactivities. The most widespread one is the classic 1,3-zwitterionic type of reactivity that can be implemented under almost any reaction conditions (Scheme A). − Recently, our team expanded the capabilities of ACDC chemistry by implementing the second principal type of reactivity through the generation of 1,2-zwitterionic intermediates in reactions with various substrates (Scheme A). As a rule, reactions of this type are performed using gallium halides as the Lewis acids. − Other types of reactivities are usually reduced to the first two with further branching based on the characteristics of the process, substrates, and substituents in the DAC itself.…”

Green and Facile Synthesis of Spirocyclopentanes Through NaOH-Promoted Chemo- and Diastereo-Selective (3 + 2) Cycloaddition Reactions of Activated Cyclopropanes and Enamides

“…Cyclopropanes are important building blocks in organic synthesis (Sohn and Bode, 2006 ; Bode and Sohn, 2007 ; Li et al, 2009 ; Lv et al, 2011 ; Sparr and Gilmour, 2011 ; Halskov et al, 2015 ; Sanchez-Diez et al, 2016 ; Blom et al, 2017 ; Apel et al, 2019 ). Especially, the cyclopropanes bearing both an electron-donating and an electron-withdrawing group on their cyclic structures, which are commonly named as Donor-Acceptor (D-A) cyclopropanes (Danishefsky, 1979 ; Wenkert, 1980 ; Reissig and Zimmer, 2003 ; Carson and Kerr, 2009 ; Cavitt et al, 2014 ; Nanteuil et al, 2014 ; Schneider et al, 2014 ; Grover et al, 2015 ; Talukdar et al, 2016 ; Wang and Tang, 2016 ; Werz and Biju, 2019 ), have been extensively studied in the construction of various functional molecules. D-A Cyclopropanes are conventionally activated by transition metal catalysts (Nanteuil et al, 2014 ), Lewis acids (Reissig and Zimmer, 2003 ; Carson and Kerr, 2009 ; Cavitt et al, 2014 ; Schneider et al, 2014 ; Grover et al, 2015 ; Talukdar et al, 2016 ; Wang and Tang, 2016 ; Werz and Biju, 2019 ) or amine-based organic catalysts (Halskov et al, 2015 ; Sanchez-Diez et al, 2016 ; Blom et al, 2017 ) ( Figure 2a ).…”