Synthesis of alpha-hydroxy acids by silylene transfer to alpha-keto esters: Application toward the synthesis of (+)-latifoline and ferupennin F

Treatment of allylic alpha-keto esters with silylene results in the diastereoselective formation of alpha-hydroxy acids. This transformation is postulated to occur through a silacarbonyl ylide intermediate that undergoes a 6pi-electrocyc1ization and tandem Ireland--Claisen rearrangement. A wide variety of substitution patterns on the alpha-keto esters are tolerated by the transformation, including several examples of sterically demanding substrates. Chiral alpha-keto esters afford chiral alpha-hydroxy acid products with complete stereochemical transfer. The silylene transfer methodology was utilized in an attempt to synthesize the natural product (+)-latifoline, previously reported by Wood in 2001. Unfortunately, exocyclic stereocenters in the Ireland--Claisen rearrangement reduced the diastereoselectivity of the transformation, rendering it completely unselective. An additional target, ferupennin F, was selected that avoided complications involved with the prior application. During the investigation, several gamma-lactones were synthesized diastereoselectively. Efforts towards the total synthesis of ferupennin F are ongoing.