Asymmetric synthesis of the C(6-18) bis(tetrahydropyran)spiroacetal fragment of the lituarines

Journal article

We describe efforts to achieve a multigram synthesis of the tricyclic spiroacetal core of the lituarines based on the addition of acyl anion equivalent to 4-(2-furyl)butan-2-one (18). We report the first cases of chemoselective Achmatowicz reaction in the presence of a second furan ring that lacks an α-hydroxyl group. The use of lithiated methoxyallene provides an efficient one-step conversion of ketone 18 into a tricyclic Diels-Alder adduct (27). In the final route, asymmetric cyanosilylation of ketone 29 achieved the construction of the stereogenic C(12) 3°-alcohol centre. Subsequent butenylation, diastereoselective reduction of keto-alcohol (+)-33 and alkene cross metathesis set up an oxy-Michael reaction to close the C(8-12) tetrahydropyran ring. The second ring-closure, which completed the route, was achieved by oxidative spirocyclisation following our earlier work. © 2011 Elsevier Ltd. All rights reserved.

Authors: Robertson, J; North, C; Sadig, J

• Publication status: Published
• Journal: TETRAHEDRON
• Volume: 67
• Issue: 27-28
• Pages: 5011-5023
• Publication date: 2011-07-08
• DOI: 10.1016/j.tet.2011.03.116
• EISSN: 1464-5416
• ISSN: 0040-4020
• Language: English
• Keywords: Cyanohydrin; Oxy-Michael; Achmatowicz; Asymmetric; Diastereoselective