title: Enantio- and diastereoselective additions to aldehydes using the bifunctional reagent 2-(chloromethyl)-3-(tributylstannyl)propene: application to a synthesis of the C16-C27 segment of bryostatin 1.
abstract: [reaction: see text] Reactions of the bifunctional allylstannane 2-(chloromethyl)-3-(tributylstannyl)propene with aldehydes have been examined. These generally occur in high yields using Lewis acid promoters and the products can be isolated and purified without incident. Good yields and high enantioselectivities are also realized in catalytic asymmetric allylations (CAA reactions) using the previously described BITIP catalyst system. Protection of the free hydroxyl can be accomplished without cyclization to the derived tetrahydrofuran, although this transformation is also facile. The utility of the incorporated allyl chloride functionality allows for the obvious use of such products in reactions with nucleophiles. Use of these products in a less obvious connective strategy is demonstrated in the synthesis of the C12-C27 segment of bryostatin 1 where a connective, or "lynchpin", double-allylation process was employed. The beta-hydroxy allyl chloride obtained from an initial chelation-controlled allylation of aldehyde 16 was converted to allylstannane 19 and applied in a second allylation reaction, thus allowing for a highly convergent synthesis of the bryostatin C ring backbone in a stereoselective fashion.
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, USA. keck@chemistry.utah.edu
authors.forename: Gary E
authors.initials: GE
authors.lastname: Keck
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Mark D
authors.initials: MD
authors.lastname: McLaws
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D054713:Bryostatins; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D017971:Tin Compounds / Q000737:chemistry*
chemical_list: C500472:2-(chloromethyl)-3-(tributylstannyl)propene; D000447:Aldehydes; D054713:Bryostatins; D018942:Macrolides; D017971:Tin Compounds; C046785:bryostatin 1; D011407:Propane