Synthesis of chiral chromans by the Pd-catalyzed asymmetric allylic alkylation (AAA): scope, mechanism, and applications.
The Pd-catalyzed asymmetric allylic alkylation (AAA) of phenol allyl carbonates serves as an efficient strategy to construct the allylic C-O bond allowing access to chiral chromans in up to 98% ee. The effect of pH and the influence of olefin geometry, as well as substitution pattern on the ee and the absolute configuration of the chiral chromans were explored in detail. These observations suggest a mechanism involving the cyclization of the more reactive pi-allyl palladium diastereomeric intermediate as the enantiodiscriminating step (Curtin-Hammett conditions). This methodology led to the enantioselective synthesis of the vitamin E core, the first enantioselective total synthesis of (+)-clusifoliol and (-)-siccanin, and the synthesis of an advanced intermediate toward (+)-rhododaurichromanic acid A.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Shen
Hong C
HC
Dong
Li
L
Surivet
Jean-Philippe
JP
Sylvain
Catherine
C
D000478:Alkylation; D000498:Allyl Compounds / Q000737:chemistry*; D002254:Carbonates / Q000737:chemistry*; D002384:Catalysis; D002839:Chromans / Q000138:chemical synthesis*; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry; D010636:Phenols / Q000737:chemistry; D013237:Stereoisomerism; D014966:Xanthenes / Q000138:chemical synthesis
D000498:Allyl Compounds; D002254:Carbonates; D002839:Chromans; D010636:Phenols; D014966:Xanthenes; C484981:rhododaurichromanic acid A; D010165:Palladium; C001795:siccanin