P-Stereogenic Bicyclo[4.3.1]phosphite Boranes: Synthesis and Utility of Tunable P-Tether Systems for the Desymmetrization of C₂-Symmetric 1,3-anti-Diols

Abstract

The development of P-stereogenicbicyclo[4.3.1]phosphite borane tether systems for the desymmetrization of C2-symmetric dienediols is reported. This report highlights preliminary studies including tether installation and removal, as well as chemoselective functionalization of the exocyclic olefin via diimide reduction or cross metathesis. Most notably, a divergent oxidation strategy allows for the transformation of the bicyclic phosphite borane complexes to the corresponding phosphate or thiophosphate systems, highlighting the electronic attenuation of this P-tether system.

P-Tether-Mediated, Iterative SN2′-Cuprate Alkylation Strategy to Skipped Polyol Stereotetrads: Utility of an Oxidative “Function Switch” with Phosphite–Borane Tethers

“…In the preceding report, we introduced the use of P -stereogenic, bicyclic P(III)-phosphite borane complexes as new tripodal, temporary tether systems for the desymmetriyation of 1,3- anti -diol-containing dienes, 7 and we highlighted the ability of this new P -tether system to facilitate chemoselective cross-metathesis reactions with Type I and Type II olefins 8 and undergo divergent oxidation protocols that transform the P–B bond to P=O or P=S bonds. We proposed that this oxidative “function switch” of the P -tether expands its utility, as a single synthetic strategy could employ the unique chemistries of both phosphite-borane and phosphate tethers to access fragments en route to the total synthesis of natural products.…”

“…As previously described, 7 C 2 -symmetric, 1,3- anti -diol 2 11 is coupled to commercially available allyl tetrai-sopropylphosphorodiamidite, in the presence of 1 H -tetrazole, to form the intermediate phosphite, which is complexed with BH 3 to generate pseudo- C 2 -symmetric phosphite-borane triene 3 (Scheme 1). Diastereoselective ring-closing metathesis (RCM) of triene 3 with Grubbs second generation catalyst [G-II, (ImesH 2 )(PCy 3 )(Cl) 2 Ru=CHPh] 12 smoothly provides bicyclo[4.3.1]phosphite borane 1 in excellent yield.…”

“…To probe the viability of a phosphite–borane tether-mediated competitive S N 2′-cuprate allylation, we first aimed to generate a model substrate by installing an allylic, exocyclic leaving group to simple bicyclic phosphite–borane 1 (Scheme ). As previously described, C 2 -symmetric, 1,3- anti- diol 2 is coupled to commercially available allyl tetraisopropylphosphorodiamidite, in the presence of 1 H -tetrazole, to form the intermediate phosphite, which is complexed with BH 3 to generate pseudo- C 2 -symmetric phosphite–borane triene 3 (Scheme ). Diastereoselective ring-closing metathesis (RCM) of triene 3 with Grubbs’ second-generation catalyst [G-II, (ImesH 2 )­(PCy 3 )­(Cl) 2 RuCHPh] smoothly provides bicyclo[4.3.1]­phosphite borane 1 in excellent yield.…”