Annulations leading to bicyclic dienes : Diels-Alder reactions of (some of) the dienes and dolastane diterpenoid syntheses

• Main Author: Friesen, Richard William
• Language: English
• Published: University of British Columbia 2010
• Subjects: Diolefins > Synthesis; Diels-Alder reaction
• Online Access: http://hdl.handle.net/2429/28781

The preparation of bicyclic dienes of the general structures (72), (82), (83) and (162) is described. These materials have been prepared via a novel annulation sequence involving (a) the alkylation of various carbonyl containing substances with the donor acceptor reagents (43), (44), (108)-(114) and (154), (b) the conversion of the alkylation products into the enol triflates, and (c) the palladium(O) catalyzed intramolecular coupling of the enol triflate-vinylstannane moieties via either a "one" or "two pot" process. The Diels-Alder reactions of the "parent" bicyclic diene (75), the cisoid cis diene (145) and the cisoid trans diene (146) are described. Four basic questions regarding the face selectivity, regioselectivity, stereoselectivity and comparative reactivity of the dienes in the formation of the Diels-Alder adducts of general structure (174) are addressed. The annulation sequences described above have been applied to the first total syntheses of the dolastane diterpenoids (±)-(14S)-dolasta-1(15),7,9-trien-14-ol (239) and (±)-amijitrienol (242). Thus, the substituted cycloheptanone (262), prepared in seven steps from the commercially available material (261), was converted via a series of transformations, including the newly developed annulation process, into the bicyclic diene (264). Introduction of the two appendages to (264) proceeded stereoselectively to provide the keto vinylstannane (265). Ring closure was effected with the desired stereochemistry to yield (±)-(239). A reduction, deprotection sequence afforded the ketone (249) from the diene ketal (263). A series of three steps involving an aldol condensation, Swern oxidation and stereoselective methylation provided the diketone (290). Chemo- and stereoselective reduction of (290) followed by protection of the alcohol moiety yielded the silyl ether (303). Cyclization, according to the methodology described herein, and deprotection of the silyl ether moiety produced (±)-(242). [Formula Omitted] === Science, Faculty of === Chemistry, Department of === Graduate