Stereocontrolled Synthesis of 1,3,5‐Triols by an Iteration of Asymmetric Dihydroxylation and Deoxygenation

Abstract

Asymmetric dihydroxylation of the Cγ=Cδ bonds in trans‐configured α,β,γ,δ‐unsaturated esters, carbonate formation, and Pd0‐catalyzed deoxygenation of Cγ provided α,β‐unsaturated δ‐hydroxy esters. Protection and chain‐extension provided the corresponding α,β‐unsaturated ketones. Their asymmetric dihydroxylation in the presence of phenylboronic acid delivered dioxaborolanes. SmBr2‐mediated deoxygenation of Cα, followed by Narasaka–Prasad and Claisen–Tishchenko reductions, respectively, selectively provided monoprotected 1,3syn,3,5syn‐, 1,3syn,3,5anti‐, 1,3anti,3,5syn‐, and 1,3anti,3,5anti‐configured 1,3,5‐triols. Enones with a bulky OSiR3 group at Cδ were dihydroxylated with significantly poorer syn (vs. anti) selectivities. Dominating reagent control modulated by opposing (“mismatched case”) or enhancing (“matched case”) substrate control, respectively, might be responsible.

Aldol Additions of Titanium and Boron Enolates of Achiral and Chiral δ‐Lactones to Achiral Model Aldehydes: Simple and Induced Diastereoselectivities

“…Figure 1) we investigated how their CpCl 2 Ti and Bu 2 B enolates aldol‐add to the aldehydes 22 – 24 . As a rule, these CpCl 2 Ti enolate additions proceeded well under the conditions of the corresponding prototypical aldol addition 5 → syn ‐ 7 9b (Scheme ). An exception was found in the CpCl 2 Ti enolate aldol additions of α‐methyl‐δ‐lactone ( 18 ), as detailed below.…”

“…), 24 h; addition of hexanal (2.2 equiv. ), 24 h; 82 %, anti / syn 100:0;9b d ) i Pr 2 NEt (1.6 equiv. ), n Bu 2 BOTf (1.5 equiv.…”

“…This propensity extends to anti ‐selective aldol additions from δ‐lactone analogues with an extra heteroatom in the six‐membered ring 10,13,14. Scheme illustrates these selectivities in lines 3 and 4, starting from the chiral δ‐lactones 5 9b and 6 4d. The syn and anti selectivities of these aldol additions were perfect – as perfect as the respective induced diastereoselecitivities, which arose additionally.…”

“…Bearing in mind the facts delineated so far we wondered what the scope of our syn ‐ versus anti ‐favoring aldol additions 5 → syn‐ 7 9b and 6 → anti‐ 8 4d from Scheme would be (Figure 1). Would the simple diastereoselectivity vary if our enolates originated from unsubstituted δ‐lactone ( 17 ) or α‐methyl‐δ‐lactone ( 18 ): that is, from δ‐lactones, which would aldol‐add without the interference of induced diastereoselectivity?…”

De novo synthesis of natural products via the asymmetric hydration of polyenes

“…9 More recently, Bruckner has developed a related oxidation/reduction approach to 1,3-polyols from 1,3-dienoates. 10 …”