CATALYTIC ASYMMETRIC-SYNTHESIS OF QUATERNARY CARBON CENTERS - EXPLORATORY INVESTIGATIONS OF INTRAMOLECULAR HECK REACTIONS OF (E)-ALPHA,BETA-UNSATURATED 2-HALOANILIDES AND ANALOGS TO FORM ENANTIOENRICHED SPIROCYCLIC PRODUCTS

The effect of chiral diphosphine structure, method of catalyst generat ion, reaction solvent, and HI scavenger on the formation of enantioenr iched 3,3-disubstituted 2-oxindole 5 from asymmetric Heck cyclization of 4 was studied (eq 1). Depending upon whether the HI scavenger was a silver salt or a basic tertiary amine, either enantiomer of 5 could b e formed with good selectivity using the same enantiomer of BINAP. Usi ng Pd-BINAP as catalyst, a variety of enantioenriched 3,3-disubstitute d oxindoles, indolines, and dihydrobenzofurans was prepared from (E)-a lpha,beta-unsaturated 2-haloaniline substrates (Table 5). With but one exception, cyclizations conducted in the presence of Ag3PO4 or 1,2,2, 6,6-pentamethylpiperidine (PMP) afforded opposite enantiomers of the s pirocyclic product. Which HI acceptor results in highest enantioselect ion is substrate dependent. These studies demonstrate, for the first t ime, that asymmetric Heck reactions of halide substrates can proceed w ith useful levels of enantioselectivity in the absence of silver or th allium salts.