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

作者：Robertson Jeremy^*; North Christopher; Sadig Jessie E R

来源：Tetrahedron, 2011, 67(27-28): 5011-5023.

DOI：10.1016/j.tet.2011.03.116

• Achmatowicz
• Asymmetric
• Cyanohydrin
• Diastereoselective
• Oxy-Michael

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 alpha-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 degrees-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.

• 出版日期2011-7-8