Regio‐ and Stereoselective Homologation of 1,2‐Bis(Boronic Esters): Stereocontrolled Synthesis of 1,3‐Diols and Sch 725674

Abstract

1,2-Bis(boronic esters), derived from the enantioselective diboration of terminal alkenes,c an be selectively homologated at the primary boronic ester by using enantioenriched primary/secondary lithiated carbamates or benzoates to give 1,3-bis(boronic esters), which can be subsequently oxidized to the corresponding secondary-secondary and secondary-tertiary 1,3-diols with full stereocontrol. The transformation was applied to ac oncise total synthesis of the 14membered macrolactone,S ch 725674. The nine-step synthetic route also features an ovel desymmetrizing enantioselective diboration of ad ivinyl carbinol derivative and high-yielding late-stage cross-metathesis and Yamaguchi macrolactonization reactions.Scheme 1. Homologation of organoboron compounds.

Mild Cu-Catalyzed Oxidation of Benzylic Boronic Esters to Ketones

“…This gave both ketone 28 and diol 29, formed from the remaining diboronic ester 26. This shows that unlike homologation chemistry, 21 the regioselectivity of our method appears to be dictated by the electronics of the C−B bond undergoing functionalization rather than the steric environment at boron.…”

Vinylidene Homologation of Boronic Esters and its Application to the Synthesis of the Proposed Structure of Machillene

“…A polyketide‐type substrate was also subjected to the reaction conditions, giving the desired product 3 k in 47 % yield. This substrate is notable considering the potential for β‐elimination via intermediate 8 , which was not observed under our reaction conditions . As lithiated epoxysilanes are configurationally stable at low temperature, we expected that a trans ‐substituted epoxysilane would furnish the trisubstituted ( E )‐olefin with high selectivity via intermediate 5 iii (Table B).…”

Strain-Release-Driven Homologation of Boronic Esters: Application to the Modular Synthesis of Azetidines

“…5,22 The tertiary boronic esters included tert-butyl (27), adamantyl (28), substituted cyclobutyl (29), 13 bicyclo[2.2.2]octyl (30), 23 dimethyl phenyl silyl (31), and a doubly benzylic (32) 24 boronic ester, giving the azetidine products in good to excellent yields. It was also possible to regioselectively homologate the primary boronic ester of a 1,2-bis(boronic ester), 25 giving 1,3-bis(boronic ester) 33, and perform a monohomologation of a 1,1-bis(boronic ester), 26 giving 1,2-bis(boronic ester) 34, in moderate yields.…”