A chirality transfer/transmission approach towards the total synthesis of the red fire ant queen rocognition pheromone (-)-invictolide.

Abstract

Radicals generated from the (bromomethyl)dimethylsilyl ether derivatives of 2-(alkylidene)cyclohexanols have been shown to undergo regio- and stereoselective cyclizations. The bromomethylsilyl ethers affixed equatorially on their respective cyclohexane rings undergo sluggish, yet regiospecific cyclizations exclusively through the 6-endo pathway. These diastereomeric cyclic silyl ether mixtures were oxidized in good yields to their corresponding diols. In contrast, the bromomethylsilyl ethers disposed axially on the rings underwent smooth, high-yielding cyclizations via the 6-endo and/or the 5-exo pathway depending on the steric environment surrounding the olefin. This steric environment could be manipulated in such a fashion as to generate cleanly the products of either exclusive 5-exo or 6-endo cyclization. In addition, total stereocontrol was observed for all the products isolated from these cyclizations regardless of the cyclization mode. The versatility of this $\alpha$-silyl radical cyclization process was demonstrated by its application in a stereocontrolled total synthesis of the red fire ant (Solenopsis invicta) queen recognition pheromone (-)-invictolide. In this high-yielding, $\alpha$-silyl radical cyclization, we observed complete stereocontrol at the two newly formed chiral centers. This total synthesis represents one of only four preparations of stereochemically pure, optically and biologically active (-)-Invictolide. The use of the (2,3) -Wittig rearrangement to stereoselectively install the methyl group found at C-7 on the side-chain of (-)-invictolide was also explored. The employment of a stannyl methyl allyl ether as the rearrangement substrate resulted in the stereospecific transfer of a hydroxymethyl group. A cuprate coupling was utilized to effect the two carbon homologation necessary to furnish the completed side chain. Alternatively, by employing a stannyl propyl allyl ether we were able to stereoselectively transfer, as a hydroxypropyl group, all three carbons needed for the side chain. This process, which resulted in the stereoselective formation of two chiral centers, may prove to be synthetically useful for the preparation of steroid side-chains.