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

Abstract

The synthesis of dialkyl-substituted cyclopropanes is an important challenge in synthesis with applications in drug discovery and agrochemistry. Herein, we report on the synthesis of gem-dialkyl cyclopropanes with in situ-generated dialkyl diazo compounds under Bamford−Stevens conditions. A simple cobalt catalyst was identified to be optimal to achieve high yields. Experimental and computational studies suggest the participation of a metalloradical reaction mechanism that facilitates the carbene transfer reactions and provides access to dialkyl-substituted cyclopropanes in a single step.

A visible-light-induced photosensitizer-free decarbonylative Minisci-type reaction

“…2, which implies that O 2 would not be activated. 12 The EPR signal that the alkyl radical trapped by TEMP verified that aldehydes could undergo decarbonylation easily under irradiation, which again confirmed that aldehydes act as excellent alkyl radical precursors in the photosystems. Then UV-Vis experiments were conducted.…”

Cyclopropanation with Non-Stabilized Carbenes via Ketyl Radicals

“…A steric focused investigation revealed disubstituted alkenes are also well-tolerated. For example, 1,1-disubstituted styrenes (11), simple alkenes (12), or allyl silanes (13), were all viable. Additionally, exocyclic methylenes provide rapid access to medicinally privileged spirocycles that fuse cyclopropanes with carbocycles (14), heterocycles (15), or small rings (16).…”

“… − Yet, since carbene precursors often require stabilizing groups to prevent spontaneous decomposition, lengthy synthetic sequences are frequently needed to remove these vestiges. Recent advances by the laboratories of Uyeda ( gem- dihalides), − Wilkerson-Hill (sulfones), and Koenigs/Xuan (hydrazones) now allow gem- dimethyl incorporation into cyclopropanes. However, a general solution to harness other diverse classes of nonstabilized alkyl carbenes–and avoid typical β-elimination byproducts , – remains desirable.…”

Redox Approaches to Carbene Generation in Catalytic Cyclopropanation Reactions

“…In one recent example, Zhang demonstrated asymmetric cyclopropanation reactions with trifluoromethylcarbenes using a cobalt metalloradical catalyst. [11,12] Related strategies include the oxidation of parent hydrazones [13] or conversions of primary amines to diazo compounds using NaNO 2 . [14] N-Sulfonyl triazoles or 1,2,3triazine 1-oxides may also be viewed as masked diazoalkanes via ring-opening processes.…”