Facile Synthesis of α-Boryl-Substituted Allylboronate Esters Using Stable Bis[(pinacolato)boryl]methylzinc Reagents

Abstract

Reported herein is the utilization of bis-[(pinacolato)boryl]methylzinc halides, whose structures are characterized via single-crystal X-ray analysis, as solid storable reagents for copper-catalyzed coupling with vinyliodonum salts. The reaction proceeds under mild conditions and shows broad scope with respect to vinyliodonium salts, affording various αboryl-substituted allylboronate esters in good yields. Synthetic applications of the obtained products are also demonstrated.O rganoborons are undoubtedly one of the most important classes of intermediates that are widely utilized in agroscience, material science, and medicinal chemistry. 1 Among them, allylboron compounds have attracted significant attention over the past decades, because they serve as versatile synthons in several organic transformations such as 1,2addition, allylboration, and Suzuki−Miyaura cross-coupling. 2 Consequently, extensive efforts have been devoted to the preparation of allylboron reagents; however, most of the methods are primarily concentrated on synthesizing monoboron-containing allylic compounds. 2,3 Recently, α-boryl-substituted allylboronate esters have emerged as new types of allylboron reagents. Such reagents are especially appealing, because they can undergo highly chemo-and stereoselective allylboration with aldehydes and cyclic aldimines to give δ-boryl-substituted homoallylic alcohols or amines, which allow further manipulations of the alkenyl moiety. 4 Nonetheless, a few examples have been reported for the preparation of α-boryl-substituted allylboronate esters (Scheme 1a). Wang and co-workers described a transition-metal-free coupling of α,β-unsaturated N-tosylhydrazone with B 2 pin 2 to afford a cyclic α-boryl-substituted allylboronate ester, although they included only one example. 4a Transition-metal-catalyzed double-bond transposition of homoallylic gem-diboronate esters was also developed by Murakami and Miura, 4b−d Chen, 4e and our research group. 4f However, most reagents were generated in situ before use probably because of the equilibration between homoallylic gem-diboronate esters and α-boryl-substituted allylboronate esters. In these studies, only (E)-or (Z)-α-boryl-substituted crotylboronate ester could be selectively isolated. Chen and coworkers disclosed a nickel-catalyzed 1,4-diboration of dienylboronate ester to afford (Z)-α,δ-bisboryl crotylboronate esters. 5 More recently, Meek et al. reported Pd-catalyzed crosscoupling of bis[(pinacolato)boryl]methyl lithium and β,β-

Pd‐Catalyzed Negishi Cross‐Coupling of Vinyl Bromides with Diborylmethylzinc Chloride

“…In our continuing interest in the development of chemoselective transformations of gem ‐diborylalkanes, 7,8 we recently demonstrated that diborylmethylzinc halides served as useful multi‐organometallic reagents in Pd‐catalyzed, chemoselective cross‐coupling with aryl (pseudo)halides 5b,9 . Based on this achievement, we envisaged that Pd‐catalyzed coupling of diborylmethylzinc halides with vinyl halides would offer an attractive route for the preparation of α‐boryl‐substituted allylic boronate esters (Scheme 1(b)).…”

“…More recently, transition‐metal‐catalyzed cross‐coupling approaches have also been disclosed (Scheme 1(a)). For example, our group reported Cu‐catalyzed cross‐coupling of diborylmethylzinc halides with various vinyl iodonium salts 5a . Meek and co‐workers developed Pd‐catalyzed coupling of diborylmethyllithium with 2,2‐disubstituted vinyl halides 6 .…”

Synthesis of Quaternary Carbon Stereogenic Centers by Diastereoselective Conjugate Addition of Boron-Stabilized Allylic Nucleophiles to Enones

“…The proposed reaction proceeds via a boron-stabilized allyl carbanion ( 10 ), and C–C bond formation occurs with high γ-selectivity at the more congested carbon. Of note, in a recent report of alkoxide promoted deborylative alkylation of 1,1-allyldiborons (e.g., via 10 ), C–C bond formation was found to proceed with high α-selectivity …”

“…Of note, in a recent report of alkoxide promoted deborylative alkylation of 1,1-allyldiborons (e.g., via 10), C−C bond formation was found to proceed with high α-selectivity. 22 To investigate the reactivity of boron-stabilized allylic carbanions, we began by evaluating the reaction of cyclohexenone 1 with the 1,1-diborylallylic reagent 12 to afford 13a (Table 1). From the outset, a key objective of our studies was to develop a robust process that is not only efficient but also highly diastereoselective and site-selective.…”

Highly Stereoselective Syntheses of α,α-Disubstituted (E)- and (Z)-Crotylboronates

“…One drawback of reagents I , however, is that they are chiral (when Met ≠ FG); the enantioselective preparation of such reagents is often quite challenging . As a subset of α-functionalized crotylation reagents, 1,1-diboryl alkane-derived α-boryl crotylboronates II (Scheme ) have attracted significant attention from the organic synthesis community. − One significant advantage of reagents II is that they are achiral, which greatly simplifies the syntheses of such reagents. As a result, several methods have been developed to allow access to reagents II with a stereodefined alkene group. − One logical extension of reagents II is α,α-disubstituted crotylboronate III (Scheme ).…”