Unusual effects in the pd-catalyzed asymmetric allylic alkylations: synthesis of chiral chromans.
An examination of earlier reports of poor-to-modest results using Pd-catalyzed asymmetric allylic alkylations (AAA) to effect cyclization to form tetrasubstituted carbons reveals several novel factors that can influence this class of reactions. Thus, carboxylate has a major effect on such cyclizations wherein the ee increases from 14% ee favoring the S with no carboxylate to 84% ee favoring the R enantiomer in the presence of 1 equiv of carboxylate. Changing the double bond geometry from E to Z further increases the ee to 97%. Furthermore, the chiral catalyst that forms the R enantiomer with the E-alkene forms the S enantiomer with the Z alkene. In contrast to trisubstituted alkene substrates, disubstituted ones show a decrease in ee in going from the E to Z alkenes. The role of carboxylate appears to be a ligand to Pd during the catalytic cycle, a previously unsuspected phenomenon since such reactions are generally believed to involve pi-allylpalladium cationic complexes. The dependence upon alkene geometry helps define the nature of the chiral pocket which better accommodates a Z alkene compared to an E alkene. The results are compatible with the enantiodiscriminating step being ionization which occurs by coordination of the palladium to one of the two prochiral faces of the double bond. A synthesis of (+)-clusifoliol, a constituent of a folk medicine for treatment of malignant tumors, which also assigns the absolute configuration, illustrates the utility of the method.
Trost
Barry M
BM
Department of Chemistry, Stanford Univeristy, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Shen
Hong C
HC
Dong
Li
L
Surivet
Jean-Philippe
JP
D000478:Alkylation; D000498:Allyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D002839:Chromans / Q000138:chemical synthesis*; D010636:Phenols / Q000737:chemistry*
D000498:Allyl Compounds; D002839:Chromans; D010636:Phenols