Intramolecular Asymmetric Cyclopropanation Using Air-Stable Alkylboronic Esters

Abstract

The preparation of polysubstituted bicyclo[3.1.0]hexanes starting from air-stable substituted pent-4-en-1-ylboronic acid esters has been investigated. The method involves a Matteson homologation with LiCHCl2, leading to 1-chlorohex-5-en-1-ylboronic acid ester intermediates. The subsequent intramolecular cyclopropanation step was performed in a one-pot process. With pinacol boronic esters, the cyclopropanation step was either performed thermally at 140 °C or at 70 °C after in situ transesterification to form a catechol boronic ester. This last approach is suitable for the preparation of enantioenriched bicyclo[3.1.0]hexanes using either chiral-auxiliary control or by taking advantage of the sparteine-controlled enantioselective boroalkylation of alcohols.

Access to γ‐Iodo‐gem‐Diborylated Cyclopentanes and to Bicyclic Cyclopropanes

“…This reaction was efficient with a variety of 1‐substituted vinylboronic esters and it delivered cyclopentylboronic esters possessing a vicinal iodomethyl substituent. Such γ‐iodoboronic esters are attractive precursors for a variety of transformations, including the formation of bicyclo[3.1.0]hexane fused cyclopropanes, [9–11] a framework present in a variety of natural products and biologically active molecules [12–15] . However, the efficacy of this approach was strongly hampered by the fact that only the minor trans ‐diastereomer resulting from the annulation process was undergoing the γ‐elimination leading to the desired fused cyclopropane.…”

“…The cyclopropanation reaction enabled by the 1,3‐relationship between the iodomethyl and boronic ester functionalities [9,59] should provide an access to fused bicyclic cyclopropylboronic acid derivatives [11,60–63] . Cyclopropylboronates are valuable building blocks allowing for a wide range of transformations such as conversion to cyclopropanols [64,65] and cyclopropylamines, [64,66] C−C bond formation using Matteson [67–69] and Zweifel [64] as well as Suzuki‐Miyaura [70,71] cross‐coupling reactions [65–73] .…”

Easy Access to γ-Iodo-gem-Diborylated-Cyclopentanes and Bicyclic Cyclopropanes

“…The cyclopropanation reaction enabled by the 1,3-relationship between the iodomethyl and boronic ester functionalities [9,61] should provide an access to fused bicyclic cyclopropylboronic acid derivatives. [11,[62][63][64][65] Cyclopropylboronates are valuable building blocks allowing for a wide range of transformations. [66][67][68][69][70][71][72][73][74] Recently, we briefly explored the formation of bicyclo[3.1.0]hexanes from ATRAn product (Scheme 1, A).…”

“…[8] This reaction was efficient with a variety of 1-substituted vinylboronic esters and it delivered cyclopentylboronic esters possessing a vicinal iodomethyl substituent. Such γ-iodoboronic esters are attractive precursors for a variety of transformations, including the formation of bicyclo[3.1.0]hexane fused cyclopropanes, [9][10][11] a framework present in a variety of natural products and biologically active molecules. [12][13][14][15] However, the efficacy of this approach was strongly hampered by the fact that only the minor trans-diastereomer resulting from the annulation process was undergoing the γ-elimination leading to the desired fused cyclopropane.…”