Cobalt Catalyzed Reductive Spirocyclopropanation Reactions

Abstract

Cobalt pyridineÀ 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 1,2hydride shift, which has hampered the development of SimmonsÀ Smith reactions using Zn carbenoids possessing β-hydrogen atoms.

Access to Optically Active 7-Membered Rings by a 2-Step Synthetic Sequence: Cu-Catalyzed Stereoselective Cyclopropanation of Branched 1,3-Dienes/Rh-Catalyzed Stereoconvergent [5 + 2] Cycloaddition

“…To the best of our knowledge, there is to date no example of an enantioselective cyclopropanation of branched dienes based on this approach . Of important note, the Uyeda group has recently disclosed highly regioselective cobalt-catalyzed Simmons–Smith dimethyl- and spiro-cyclopropanation of 1,3-dienes …”

“…14 Of important note, the Uyeda group has recently disclosed highly regioselective cobalt-catalyzed Simmons−Smith dimethyl-and spiro-cyclopropanation of 1,3-dienes. 15 We envisioned that a 2-step synthetic sequence consisting of a regio-, diastereo-, and enantioselective cyclopropanation of 2substituted 1,3-dienes followed by a stereoconvergent and enantiospecific [5 + 2] cycloadditionproceeding by regioselective opening of the chiral VCP generatedcould provide expedient access to synthetically useful optically active 7-membered rings. Our initial strategy was built on combining and adapting the stereochemical rationale proposed by Pfaltz for the Cu-catalyzed intermolecular cyclopropanation of olefins using chiral C 2 -symmetric (N,N) ligands 8a and the model elaborated by Wender and Houk for the intermolecular Rhcatalyzed [5 + 2] cycloaddition of VCPs with additional substituents on the cyclopropane ring.…”

Catalytic Olefin Cyclopropanation with In Situ-Generated Dialkyl Diazomethanes via Co(II)-Based Metalloradical Catalysis

“…In a related context, the Zhang and Bruin groups have reported a series of studies on cobalt-catalyzed carbene transfer reactions of diazoacetates where a metalloradical species is involved to achieve cyclopropanation reactions without participation of a conventional singlet carbene intermediate (Scheme b) . Moreover, the Uyeda group has recently uncovered that gem -dihalogenated alkanes can be employed as precursors of unstabilized carbenes in cyclopropanation reactions using stoichiometric amounts of reducing agents …”

Catalytic Asymmetric Cyclopropanations with Nonstabilized Carbenes

“…17 Recognizing the potential value of sp 3 -rich polycyclic frameworks in drug discovery, 18 we sought to apply this reaction to the synthesis of chiral spirocyclopropanes (Figure 3A). 19 The requisite gem-dichlorocycloalkanes can be readily synthesized in one step from their corresponding cyclic ketones using WCl 6 . 20 With little modification to the reaction conditions, spirocyclopropanes 30−37 were prepared with high levels of enantioselectivity.…”