Asymmetric Synthesis of Tertiary and Secondary Cyclopropyl Boronates via Cyclopropanation of Enantioenriched Alkenyl Boronic Esters

Abstract

The cyclopropanation of alkenyl boronates and subsequent derivatization of the boronate handle are a convenient strategy to quickly build molecular complexity and access diverse compounds with a high sp 3 fraction. Herein, we describe the asymmetric cyclopropanation of enantioenriched hydrobenzoinderived alkenyl boronic esters toward the synthesis of tertiary and secondary cyclopropyl boronates.

Enantioselective α-Boryl Carbene Transformations

“…Despite variations in substituent nature on the phenyl ring, comparable high yields and ee values were observed (30−33). However, the bulky triethylsilane resulted in a lower yield (55%), maintaining a high enantioselectivity (34). Similarly, symmetrical 1-boryl-3,3-dialkyl cyclopropenes and 3-aryl-3-alkyl cyclopropenes exhibited substantial yields and ee, with the latter exclusively producing E-type allylic gemborylsilanes (35−45).…”

“…Cyclopropyl boronates, promising building blocks for numerous cyclopropane-containing bioactive compounds, 32,33 are typically scarce in enantioselective synthetic protocols. 34 Addressing this gap, we explored asymmetric cyclopropanation reactions involving alkenes and carbene derivatives from 1borylcyclopropenes (Scheme 3a). Utilizing the Cu(MeCN) 4 PF 6 /L1 system, previously successful in B−H and Si−H insertion reactions, we achieved high yields and selectivities in creating tertiary cyclopropyl boronates 46−78, even tolerating diverse functional groups (49−57).…”

“…Cyclopropyl boronates, promising building blocks for numerous cyclopropane-containing bioactive compounds, , are typically scarce in enantioselective synthetic protocols . Addressing this gap, we explored asymmetric cyclopropanation reactions involving alkenes and carbene derivatives from 1-borylcyclopropenes (Scheme a).…”

Expedient Synthesis of 6‐Functionalized Azabicyclo[4.1.0]heptane Derivatives

“…The historically first method relied on the DBU‐mediated intramolecular alkylation of ethyl γ‐iodo carboxylate (Scheme 1, A ) [26,27] . Subsequently, Simmons–Smith cyclopropanations of N ‐protected 4‐piperidinone silyl enol ether [28] and unsaturated boronates [29,30] with diiodomethane and ZnEt 2 were reported (Scheme 1, B ). Later, an increased outcome of the target boronate was achieved through palladium‐catalyzed cyclopropanation of an unsaturated pinacol boronate with diazomethane (Scheme 1, C ) [31] .…”

Anion-Mediated, Stereospecific Synthesis of Secondary and Tertiary Cyclopropylboronates from Chiral Epoxides and gem-Diborylalkanes

“…As a result, considerable effort has been directed toward the development of methods for synthesizing enantioenriched cyclopropylboronates. Despite these advances, most methods have focused on the preparation of enantioenriched secondary cyclopropylboronates, while the methods for synthesizing enantioenriched tertiary cyclopropylboronates have been rarely studied . Herein, we describe the stereospecific synthesis of secondary and tertiary cyclopropylboronates using optically pure epoxides and ( gem -diborylalkyl)­lithiums under transition-metal-free conditions .…”