Asymmetric synthesis of a carbon(9)-carbon(25) fragment of (+)-calyculin A. Iodine monobromide (IBr) at low temperature: A superior protocol for diastereoselective cyclizations of homoallylic carbonates

• Main Author: Duan, Jingwu
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-1992
• Subjects: Organic chemistry
• ISBN: 9798460484737

Chapter one describes an asymmetric synthesis of a C(9)-C(25) fragment of (+)-calyculin A. The highly functionalized C(16)-C(25) spiroketal ((+)-103) was constructed by a convergent and expeditious approach. Key features included: (A) development of the IBr/toluene protocol for diastereoselective iodo carbonate cyclizations during the synthesis of epoxide (+)-116; (B) efficient coupling of dithiane 144 and epoxide (+)-116; (C) a highly stereoselective introduction of the C(14)-C(15) vinyl group; and (D) a one-pot multi-deprotection spirocyclization protocol to complete the synthesis of spiroketal (+)-103. Following the epoxidation of (+)-103, the crucial coupling of epoxide (+)-106 with a higher order mixed cuprate derived from vinyl iodide ($-$)-105 proved to be highly efficient (95%). Further elaboration of (+)-213 provided 216, a stereochemically fully endowed C(9)-C(25) segment of (+)-calyculin A. Chapter II discusses the discovery, solvent and temperature effects, and scope and limitations of iodine monobromide-induced diastereoselective cyclizations of homoallylic carbonates. In contrast to the reported iodine/$-$20$\sp\circ$C conditions which work well only in acetonitrile, IBr-induced cyclizations proceed smoothly in a wide variety of solvents. The most selective conditions are IBr in toluene at $-$80 to $-$85$\sp\circ$C. In general, the newly developed IBr/toluene/$-$80 to $-$85$\sp\circ$C protocol furnished significantly improved diastereoselectivity over the reported iodine/acetonitrile/$-$20$\sp\circ$C conditions. (Abstract shortened by UMI.)