Chiral β-amino alkylboronates are of great interest as useful building blocks of β-amino alcohols and α-amino acids. Moreover, incorporation of β-amino alkylboronates into peptide chains provides a strategy for enzymatic inhibition. Yet, unlike the lower homologs α-amino alkylboronates, few methods to synthesize chiral β-amino alkylboronates have been reported. Our approach to access optically enriched β-amino alkylboronates employs the diastereoselective nucleophilic addition of lithiated 1,1-diborylalkanes to chiral N-tert-butanesulfinyl imines. Addition onto various N-tert-butanesulfinyl aldimines (aryl, alkynyl, alkenyl and alkyl) affords β-sulfinimido bis(boronates) in good to high yield (72–98%) with high diastereoselectivity (&gt;20:1–10:1 dr). A stereocontrolled protodeboronation subsequently affords the corresponding chiral β-amino alkylboronates in moderate to high yield (52–100%) with moderate to high diastereoselectivity (&gt;20:1–5:1 dr). Mechanistic studies were achieved to probe the origin of the diastereoselection in the protodeboronation. As demonstrated in a series of applications, the chiral β-amino alkylboronate products can be transformed into chiral β-amino alcohols via oxidation of the Bpin unit. Moreover, an optically enriched β-amino alkylboronate product was utilized to synthesize an α,β-disubstituted peptidyl β-amino alkylboronate reported to be a potent anti-tubercular agent.

Diastereocontrolled deboronation of β-sulfinimido bis(boronates): A general stereoselective method to access α,β-disubstituted β-amino alkylboronates

256th National Meeting (2018)

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