A Modular Access to 1,2‐ and 1,3‐Disubstituted Cyclobutylboronic Esters by Consecutive Radical Additions

Abstract

A modular approach to substituted cyclobutylboronic esters is described. It proceeds by successive intermolecular radical additions of xanthates to pinacolato 1‐cyclobutenylboronate and to pinacolato bicyclo[1.1.0]but‐1‐ylboronate. Success hinges on tuning the stability of the α‐boryl radical by exploiting the stabilizing influence of the trivalent boronic ester and the slightly destabilizing cyclobutane, which increases the σ‐character of the radical. Reductive removal of the xanthate group finally provides a range of 1,2‐ and 1,3‐disubstituted cyclobutylboronic esters. The contrast with cyclopropylboronic esters is striking, since the strong destabilization by the highly strained cyclopropane ring allows the first radical addition to take place but not the second. Furthermore, the first adducts are geminal xanthyl boronic esters that can be converted into cyclobutanones. This chemistry furnishes cyclobutylboronic esters that would be quite difficult to obtain otherwise and thus complements existing methods.

Synthesis and Applications of Bicyclo[1.1.0]butyl and Azabicyclo[1.1.0]butyl Organometallics

“…This species was subsequently shown to generate boronate complexes with a range of heteroatom‐centered nucleophiles which directly underwent strain‐release‐driven 1,2‐metallate rearrangements upon protonation of the bicyclo[1.1.0]butane fragment (Scheme 27bi). An alternative application of BCB‐Bpin ( 108 ) was reported by Zard and coworkers who demonstrated that this fragment could undergo radical addition reactions with alkyl xanthantes (Scheme 27bii) [124] . The relative stability of the resulting α‐boryl cyclobutane radical facilitates this initial addition allowing it to act as a Giese‐type acceptor.…”

“…[27] These side reactions were inhibited by reducing the π-acidity of the intermediate palladium complexes by employing the electron-rich trifurylphosphine (tfp) ligand and limiting the lifetime of Pd(II) intermediates by using organozinc complexes to enhance the rate of transmetalation. This methodology allowed access to a variety of novel disubstituted aryl-bicyclo[1.1.0]butanes, with the synthetic utility of these species demonstrated by their transformation to cyclobutanes (124), cyclobutenes (125), sulfone functionalized bicyclo[1.1.0]butanes (126) and difluorobicyclo[1.1.1]pentanes (127, Scheme 31b). [49]…”

Photochemical [2+2] Cycloaddition of Alkynyl Boronates

“…[18,21,22] Cyclobutane-derived boronates and their preparation are broadly described in the literature. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] On the contrary, the synthesis of cyclobutene-derived boronates and their applications are very scarce. Thus, lithiation of iodo-(1 a) [43] or bromocyclobutene (1 b) [44,45] and subsequent treatment with trialkoxy borates resulted in ionic boronate 2 a, [43] or in neopentyl-protected boronate 2 b after transesterification, [44,45] respectively (Scheme 1, A).…”

Generation and Application of Homoallylic α,α‐Diboryl Radicals via Diboron‐Promoted Ring‐Opening of Vinyl Cyclopropanes: cis‐Diastereoselective Borylative Cycloaddition**

“…The ability of boron atom to modulate the formation and reactivity of a radical at an adjacent carbon provides unique opportunities to expand the applications of organoborons in new directions. Previous approaches [1–2] (Scheme 1a–b) to access α‐boryl radicals have employed one of the following strategies: i) halogen atom abstraction of α‐halo borons, [6–8] ii) H‐atom abstraction of secondary alkyl boronates, [9] iii) C−S bond cleavage of boryl xanthates, [10] iv) radical addition/HAT to vinyl boronates [1,11–16] and v) C−B bond cleavage of unsymmetrical geminal diborons [17] . The ensuing α‐boryl stabilized carbon‐centered radicals were used in addition reaction with alkenes, [6–7,10,17] C−X bond formation [9] or SET/proton capture [12] .…”

“…Previous approaches [1–2] (Scheme 1a–b) to access α‐boryl radicals have employed one of the following strategies: i) halogen atom abstraction of α‐halo borons, [6–8] ii) H‐atom abstraction of secondary alkyl boronates, [9] iii) C−S bond cleavage of boryl xanthates, [10] iv) radical addition/HAT to vinyl boronates [1,11–16] and v) C−B bond cleavage of unsymmetrical geminal diborons [17] . The ensuing α‐boryl stabilized carbon‐centered radicals were used in addition reaction with alkenes, [6–7,10,17] C−X bond formation [9] or SET/proton capture [12] . While these protocols represent significant advances, they mainly provide access to radicals having a single boryl group at the α‐position ( A / A′ Scheme 1a).…”