Borylated Cyclopentanes via Atom Transfer Radical [3+2] Annulation

Abstract

Abstract. An atom transfer radical [3+2] annulation (ATRAn) reaction involving alkenyl boronic esters and homoallylic iodides provides a rapid access to polysubstituted borylated cyclopentanes. A variety of α‐substituted vinylboronic esters are suitable substrates and offer unique opportunities for further modification of the formed 5‐membered ring. For instance, the oxidation of the boronic ester to an alcohol allows the preparation of products that corresponds to an annulation involving the enol form of acetone. Substitution of the iodide by a nucleophile such as lithium methoxide without modifying the boronic ester moiety is also feasible. Finally, by using a (3‐acetoxyprop‐1‐en‐2‐yl)boronic ester, a facile 1,2‐elimination reaction provided a methylenecyclopentane. In this case, the alkenylboronate radical trap acts as an equivalent to allene, a building block so far elusive for preparative radical reactions.

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

“…The radical annulation reaction was carried out with gemdiborylethene 1 using Et3B and di-tert-butylhyponitrite (DTBHN) to initiate the reaction, in analogy to the reaction conditions previously reported for simple mono-borylalkenes. [8,56] The scope of the annulation reaction was investigated with a series of electrophilic radical precursors (Scheme 3). The use of dimethyl 2-allyl-2-iodomalonate 2a and its benzyl ester analogue 2b delivered the desired cyclopentanes 3a and 3b in high yields.…”

“…[6,7] Recently, we have demonstrated that mono-borylated cyclopentanes can easily be prepared via an atom transfer radical annulation (ATRAn) process involving homoallylic iodides and alkenylboronic esters (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.…”

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

“…The radical annulation reaction was carried out with gem-diborylethene 1 using Et 3 B and di-tert-butylhyponitrite (DTBHN) to initiate the reaction, in analogy to the reaction conditions previously reported for simple mono-borylalkenes. [9,8] The scope of the annulation reaction was investigated with a series of electrophilic radical precursors (Scheme 3). The use of dimethyl 2allyl-2-iodomalonate 2 a and its benzyl ester analogue 2 b delivered the desired cyclopentanes 3 a and 3 b in high yields.…”

“…[65][66][67][68][69][70][71][72][73] Recently, we briefly explored the formation of bicyclo[3.1.0]hexanes from ATRAn product (Scheme 1, A). [8] The bicyclo[3.1.0]hexane skeleton monoalkylated at the bridgehead position is found in many natural products such as thujone, sabinene, and related terpenoids. The reaction was low yielding due to the stereoelectronic requirements for this S N i reaction, which was reported to proceed via inversion at both the borylated and halogenated carbon atoms.…”

“…[6,7] Recently, we have demonstrated that mono-borylated cyclopentanes can easily be prepared via an atom transfer radical annulation (ATRAn) process involving homoallylic iodides and alkenylboronic esters (Scheme 1, A). [8] This reaction was efficient with a Scheme 1. ATRAn reaction with vinylboronic esters and radical addition to gem-diborylalkenes.…”