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. 2022 Apr 21;2(4):667-678.
doi: 10.1016/j.checat.2022.01.002. Epub 2022 Feb 4.

Catalytic Reductive Carbene Transfer Reactions

Christopher Uyeda  1 , Annah E Kalb  1
Affiliations

Catalytic Reductive Carbene Transfer Reactions

Christopher Uyeda et al. Chem Catal. .

Abstract

Efforts to develop catalytic carbene transfer reactions have largely relied on the use of diazo precursors. However, diazoalkanes are susceptible to undergoing violent exothermic decomposition unless they contain stabilizing substituents. Consequently, most synthetic methods are restricted to diazoacetates or related derivatives. In this Perspective, we describe an alternative approach to carbene transfer catalysis based on the generation of metal carbenoids from gem-dihaloalkanes and gem-dihaloalkenes. These precursors are readily available and stable in unsubstituted form or with a variety of donor and acceptor substituents. Using this approach, it is possible to design cyclopropanation reactions with non-stabilized carbenes, such as methylene, isopropylidene, and vinylidene. Furthermore, due to the distinct mechanistic pathways of these reactions, novel modes of cycloaddition can be carried out, including [4 + 1]-cycloadditions.

Keywords: carbenes; cycloadditions; transition metal catalysis.

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Conflict of interest statement

DECLARATION OF INTERESTS The authors declare no competing interests.

Figures

Figure 1.
Figure 1.. Redox neutral and reductive strategies for carbene transfer.
(A) Redox neutral carbene transfer reactions using diazoalkanes and other reagents. Recent examples of enantioselective cycloaddition and bond-insertion reactions. (B) Reductive carbene transfer reactions using stoichiometric metal carbenoids. Applications in the synthesis of biologically active cyclopropanes.–
Figure 2.
Figure 2.. Generation and Reactivity of Metal Carbenes and Carbenoids from gem-Dihaloalkanes.
(A) Metal carbenoids, terminal metal carbenes, and bridging metal carbenes generated from the oxidative addition of CH2Cl2. (B) Stoichiometric reductive carbene transfer reactions.
Figure 3.
Figure 3.. Nickel-Catalyzed Reductive Cyclopropanation Reactions.
(A) Nickel-catalyzed reductive cyclopropanation reactions of electron-deficient alkenes. (B) Evidence supporting the intermediacy of a nucleophilic nickel carbene that reacts by a [2 + 2]-cycloaddition then C–C reductive elimination pathway.
Figure 4.
Figure 4.. Cobalt-Catalyzed Reductive Cyclopropanation Reactions.
(A) Cobalt-catalyzed reductive cyclopropanation, dimethylcyclopropanation, and spirocyclopropanation reactions. (B) Proposed activation of gem-dihaloalkanes by a Co(I) complex to form a Co(carbenoid) or Co(carbene) intermediate.
Figure 5.
Figure 5.. Dinickel-Catalyzed Reductive Vinylidene Transfer Reactions.
(A) Isomerization of vinylidenes to alkynes via the Fritsch–Buttenberg–Wiechell (FBW) rearrangement. (B) Dinickel-catalyzed vinylidene [2 + 1]- and [4 + 1]-cycloaddition reactions. (C) Asymmetric vinylidene cycloadditions using chiral dinickel catalysts. (D) Proposed stepwise mechanism for cyclopropanation. Migratory insertion of an alkene into a Ni2(vinylidene) followed by C–C reductive elimination.
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