Oligomeric procyanidins containing 4.alpha.-linked epicatechin units are rare in nature and have hitherto not been accessible through stereoselective synthesis. Provided herein is the preparation of the prototypical dimer, epicatechin-4.alpha.,8-epicatechin, by reaction of the protected 4-ketones with aryllithium reagents derived by halogen/metal exchange from the aryl bromides. Removal of the 4-hydroxyl group from the resulting tertiary benzylic alcohols is effected by tri-n-butyltin hydride and trifluoroacetic acid in a completely stereoselective manner, resulting in hydride delivery exclusively from the .beta. face.
This application is a divisional application of prior application Ser. No. 10/214,830 filed Aug. 8, 2002, now U.S. Pat. No. 6,720,432 issued Apr. 13, 2004, which is a divisional application of prior application Ser. No. 09/655,360 filed Sep. 5, 2001, now U.S. Pat. No. 6,476,241 issued Nov. 5, 2002.
Processes are disclosed for the production of linear and branched procyanidin oligomers having "n" procyanidin monomeric units where n is 2 to 18. The processes include coupling protected, activated monomers with an unprotected monomer to produce a partially protected (4.fwdarw.8) dimer. The dimer is optionally blocked, coupled with an activated protected monomer to produce a partially protected, optionally blocked trimer, and deprotected. The steps can be repeated to produce higher oligomers. Processes are also provided for producing (8.fwdarw.8), (8.fwdarw.6), and (6.fwdarw.6) dimers and doubly branched oligomers. Crystalline 8-bromo tetra-O-benzyl (-)-epicatechin is produced under certain conditions.
