Evaluation of possible intramolecular [4+2] cycloaddition routes for assembling the central tetracyclic core of the potent marine antfinflammatory agent mangicol A

• Published in: Tetrahedron Vol. 62; no. 22; pp. 5178 - 5194
• Main Authors: Pichlmair, Stefan, de Lera Ruiz, Manuel, Basu, Kallol, Paquette, Leo A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier 29.05.2006
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; CONVENIENT SYNTHESIS; ORGANIC-SYNTHESIS; ASYMMETRIC-SYNTHESIS; ACID; DIELS-ALDER REACTIONS; ENANTIOSELECTIVE SYNTHESIS; intramolecular aldol cyclizations; EFFICIENT SYNTHESIS; PD-CATALYZED CYCLOISOMERIZATION; mangicols; enantioselective diene synthesis; chiral nonracemic substituted cyclopentadienones; ALLYLIC ALCOHOLS; Pd-catalyzed enyne cyclization; KINETIC RESOLUTION
• ISSN: 0040-4020
• DOI: 10.1016/j.tet.2005.11.096

A plan for enantioselective construction of the mangicol A framework by means of intramolecular Diels-Alder cycloaddition is outlined. First to be assembled is the enantiopure cyclopentenecarboxylic acid 16. Of the several approaches targeting the 1,3-diene component 56, only that involving palladium-catalyzed enyne cyclization proved successful. Following the coupling of 16 to 56, we were unable to bring about any detectable level of (4 pi+2 pi) cycloaddition. Activation of the diene by incorporation of an OSiEt3 substituent on a terminal sp(2)-hybridized center likewise proved unsuccessful. Further facilitation was sought in the form of cyclopentenonecarboxylate 66. However, thermal activation, Lewis acid catalysis, and high-pressure conditions proved ineffective and did not lead to C-C bond formation. These studies serve to underscore the extent to which steric complications can complicate matters and the extent to which they must be skirted to arrive at the title compound. (c) 2006 Elsevier Ltd. All rights reserved.