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. 2020 Jan 23;362(2):348-352.
doi: 10.1002/adsc.201901293. Epub 2019 Nov 6.

Cobalt Catalyzed Reductive Spirocyclopropanation Reactions

Jacob Werth  1 , Kristen Berger  1 , Christopher Uyeda  1
Affiliations

Cobalt Catalyzed Reductive Spirocyclopropanation Reactions

Jacob Werth et al. Adv Synth Catal. .

Abstract

Cobalt pyridine-diimine (PDI) complexes catalyze the reductive spirocyclopropanation of terminal 1,3-dienes. gem-Dichlorocycloalkanes serve as carbene precursors and Zn is used as a terminal electron source. The reaction is effective for a range of gem-dichloro partners including those containing sulfur and nitrogen heterocycles. An example of an intramolecular Rh-catalyzed [5 + 2]-cycloaddition of a vinyl spirocyclopropane is demonstrated, providing rapid access to a complex tricyclic framework. Overall, this catalyst system is capable of suppressing the kinetically facile 1,2-hydride shift, which has hampered the development of Simmons-Smith reactions using Zn carbenoids possessing β-hydrogen atoms.

Keywords: carbenes; carbenoids; cobalt; cyclopropanes; spiro compounds.

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Figures

Figure 1.
Figure 1.
Spirocyclopropanes in natural products and pharmaceutical compounds. Spirocyclopropanations of α,β unsaturated esters using diazocycloalkanes,[7] and catalytic reductive spirocyclopropanations using 1,1-dichlorocycloalkanes.
Figure 2.
Figure 2.
Substrate Scope Studies. Reaction conditions: 0.14 mmol of the 1,3-diene substrate, 1,1-dichlorocycloalkane (1.25 equiv), Zn (2.0 equiv), ZnBr2 (0.5 equiv), catalyst 9 (10 mol%), room temperature, 24 h. Isolated yields were determined following purification by column chromatography.
Figure 3.
Figure 3.
(a) Spirocyclopropanation reactions of activated alkenes, including (vinyl)Bpin. (b) Selective monocyclopropanation of a triene and Rh-catalyzed [5 + 2]-cycloaddition.
Figure 4.
Figure 4.
(a) Mechanistic possibilities for the cobalt-catalyzed spirocyclopropanation reaction. (b) Optimized geometries for isomeric Co(C5H8)Cl2 and Co(C5H8Cl)Cl complexes (S = 1/2, BP86/6–311G(d,p)/SMD(THF)//BP86-D3BJ/6–311G(d,p) level of DFT). Calculated relative energies are shown in kcal/mol.
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