Short Stereoselective Synthesis of the Phytophthora Universal Mating Hormone α1 Using Lithiation/Borylation Reactions

Abstract

The universal mating hormone a 1 of the virulent plant pathogen Phytophthora has been synthesized in 12 steps and 28 % overall yield. Key CÀC bond-forming steps involved the use of two lithiation/borylation reactions to couple together enantioenriched building blocks, one of which also set up the stereochemistry of the tertiary alcohol at C11. Detailed analysis showed that the diastereomeric purity of the target molecule was > 91 %, the highest obtained to date.

Enantioselective Copper(I)-Phosphoramidite Catalyzed Addition of Alkylzirconium Species to Acyclic Enones

“…There is a need to develop new reliable methods for the stereoselective construction of substituted linear alkanes, both for structure determination and for the synthesis of natural products and derivatives; the relative and absolute stereochemistry of 1 , for example, is not known. In the case of 2 , the combination of important biological activity and the difficulty of determining the relative and absolute configurations of stereogenic centers embedded in saturated alkyl chains have attracted considerable attention …”

Reagent-Controlled Lithiation–Borylation

“…Aggarwal used this methodology in the asymmetric synthesis of the Phytophthora universal mating hormone α-1 74 (Scheme 19) [47]. The synthesis started from the enantioenriched bis-carbamate 75 (prepared in five steps from citronellal).…”

Chelation-Assisted Substrate-Controlled Asymmetric Lithiation-Allylboration of Chiral Carbamate 1,2,4-Butanetriol Acetonide

“…Aggarwal and co-workers have investigated the chelation-assisted substrate-controlled (CASC), asymmetric lithiation, and allylboration through less-sterically demanding chiral carbamates and explored its application for selectively making C-C bonds [9,10,11,12,13,14,15,16,17,18]. Previously, we have described this methodology to obtain highly selective products through substituted boranes ( trans -alkenyl-9-BBN) and boronic esters and their reactions with sparteine-complexed lithiated carbamates [19].…”