Development of aliphatic alcohols as nucleophiles for palladium-catalyzed DYKAT reactions: total synthesis of (+)-hippospongic acid A.
The ability to use aliphatic alcohols as competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric transformation of Baylis-Hillman adducts is explored. High yield and enantioselectivity is obtained for both the kinetic transformation and dynamic kinetic transformation. The absolute stereochemistry of the products is used to explore the reactive conformation of 2-substituted pi-allyl complexes with DPPBA-based chiral ligands. The utility of this method is further demonstrated in the context of a concise total synthesis of the gastrulation inhibitor (+)-hippospongic acid A. The synthesis features three palladium-catalyzed allylic alkylation reactions to introduce three different bond types: C-S, C-H, and C-O.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, CA 94305, USA. bmtrost@stanford.edu
Machacek
Michelle R
MR
Tsui
Hong C
HC
D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry*; D000478:Alkylation; D000498:Allyl Compounds / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis*; D002384:Catalysis; D007700:Kinetics; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism; D014315:Triterpenes / Q000138:chemical synthesis*
D000438:Alcohols; D000498:Allyl Compounds; D002264:Carboxylic Acids; D014315:Triterpenes; C459583:hippospongic acid A; D010165:Palladium