Synthesis of Cyclopentenones with Reverse Pauson–Khand Regiocontrol via Ni-Catalyzed C–C Activation of Cyclopropanone

Abstract

A formal [3+2] cycloaddition between cyclopropanone and alkynes via Ni-catalyzed C-C bond activation has been developed, where 1-sulfonylcyclopropanols are employed as key precursors of cyclopropanone in the presence of trimethylaluminum. The transformation provides access to 2,3-disubstituted cyclopentenones with complete regiocontrol, favoring reverse Pauson-Khand products where the large substituent is located at the 3-position of the ring. In the process, the trimethylaluminum additive is thought to play multiple roles, including as a Brønsted base triggering the equilibration to cyclopropanone and liberation of methane, as well as a source of Lewis acid to activate the carbonyl group toward Ni-catalyzed C-C activation.

Gold Self‐Relay Catalysis Enabling [3,3]‐Sigmatropic Rearrangement/Nazarov Cyclization and Allylic Alkylation Cascade for Constructing All‐Carbon Quaternary Stereocenters

“…Moreover, this skeleton could serve as a powerful intermediate to synthesize some natural products and pharmaceuticals [ 6‐8 ] due to the wide diversity of potential functionalizations at the enone unit. As such, great efforts have been made over the last decades to establish state‐ of‐art and reliable methods for the fabrication of such scaffolds, which mainly include Pauson−Khand reactions, [ 9‐13 ] Nazarov cyclizations, [ 14‐18 ] Rautenstrauch Rearrangements, [ 19‐21 ] organocatalyzed reactions, [ 22‐25 ] functionalizations of the existing cyclopentenone unit [ 26‐27 ] as well as cyclization of acyclic substrates. [ 28‐34 ] Despite these remarkable achievements, the continuous development of new synthetic approaches for assembling functionalized cyclopentenones would be particularly useful, given their potential application and pharmaceuticals.…”

Synthesis and Applications of Cyclopropanones and Their Equivalents as Three-Carbon Building Blocks in Organic Synthesis

“…In 2020, Lindsay and co-workers disclosed a novel Nicatalyzed formal (3+2) cycloaddition of cyclopropanone and internal alkynes via C-C bond activation, employing 1sulfonylcyclopropanol 101 as cyclopropanone equivalent and providing access to 2,3-disubstituted cyclopentenones 231 (Scheme 59). 88 Notably, the corresponding products are formed with complete regiocontrol, favoring cyclopen-…”

Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs

“…For the generation of a diverse scaffold, other NIMCRs implemented are, namely, Pavarov-3CR, Dobener-3CR, Betti-3CR, and Petasis-3CR ( Figure 4 ). For further information on NIMCRs chemistry, the reader is directed toward comprehensive review articles and other very interesting recent publications [ 89 , 90 , 92 , 93 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 ].…”