Nickel‐Hydride‐Catalyzed Diastereo‐ and Enantioselective Hydroalkylation of Cyclopropenes

Abstract

Cyclopropanes are structural motifs that are widely present in natural products and bioactive molecules, and they are also tremendously useful building blocks in synthetic organic chemistry. Asymmetric synthesis of cyclopropane derivatives has been an intensively researched area over the years, but efficient asymmetric preparation of alkylcyclopropane scaffolds remains a challenging topic. Herein, we report a nickelhydride-catalyzed enantioselective and diastereoselective hydroalkylation of cyclopropenes for facile synthesis of chiral alkylcyclopropane motifs. The reported method is efficient and versatile, taking place under mild reaction conditions, and having broad applicability and excellent functional group tolerance.

Cobalt‐Catalyzed Diastereo‐ and Enantioselective Hydroarylation of Cyclopropenes with Arylboronic Acids

“…In the context of catalytic enantioselective functionalization of cyclopropenes, Rh-catalyzed hydrostannation, [8] hydroboration, [9] hydrothiolation, [10] hydroformylation, [11] hydroacylation [12] and hydroarylation, [13] Cu-catalyzed hydroboration, [14] hydronitronylation, [15] carbocupration, [16] carbozincation, [17] carbomagnesiantion [18] and hyroallylation, [19] Fe- [20] and Pd-catalyzed carbozincation, [21] hydroalkynylation, [22] hydrophosphination [23] and lanthanide-catalyzed hydroamination, [24] hydroalkynylation, [25] and addition of 2methyl azaarenes, [26] Co-catalyzed hydroalkenylation [27] and hydrosilylation, [28] Ni-catalyzed hydroalkylation, [29] hydroaryloxyand hydroalkoxycarbonylation [30] and NHC-catalyzed hydroacylation [31] have been reported for enantioselective synthesis of a variety of functionalized cyclopropanes. Although enantioselective hydroboration of cyclopropenes followed by Pd-catalyzed cross-coupling with aryl halides represents an indirect approach to incorporate an aryl unit on the threemembered rings, [8,14,26] a more general and step-economic solution to this problem is the utility of more robust aryl boronic acids with higher functional group tolerance and diversity as nucleophiles for catalytic enantioselective hydroarylation of cyclopropenes.…”

Cobalt‐Catalyzed Facial‐Selective Hydroalkylation of Cyclopropenes

“…For example, Marek and Lu independently achieved the CuH and NiH-catalyzed cyclopropene hydroalkylation with alkyl electrophiles in excellent diastereo-and enantioselectivity. [11,12] However, due to their inherent properties, CuH and NiH catalysis have room for improvement in the substrate scope. CuH catalysis was applicable for activated hyperactive allyl electrophiles.…”

“…Among them, metal‐hydride‐catalyzed cyclopropene hydroalkylation is versatile and highly efficient in accessing multi‐substituted cyclopropanes (Figure 1C). For example, Marek and Lu independently achieved the CuH and NiH‐catalyzed cyclopropene hydroalkylation with alkyl electrophiles in excellent diastereo‐ and enantioselectivity [11, 12] . However, due to their inherent properties, CuH and NiH catalysis have room for improvement in the substrate scope.…”

Copper-Catalyzed Hydroamination: Enantioselective Addition of Pyrazoles to Cyclopropenes

“…The hydrofunctionalization of cyclopropenes represents a versatile strategy for accessing chiral cyclopropanes. − Most relevant to our current study, Hou and co-workers disclosed the asymmetric coupling of cyclopropenes with secondary amines (e.g., morpholine, pyrrolidine, and dibenzylamines) by using a rare-earth metal catalyst (Sm) . Buchwald and co-workers developed an enantioselective hydroamination of 1-silyl- or 1-aryl-substituted cyclopropenes using Cu–H catalysis, with O -benzoylhydroxylamines as oxidants and silanes as the stoichiometric reductant .…”