Ruthenium-Catalyzed Alder Ene Type Reactions. A Formal Synthesis of Alternaric Acid

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• 作者：Barry M. Trost ; Gary D. Probst ; and Andreas Schoop
• 刊名：Journal of the American Chemical Society
• 出版年：1998
• 出版时间：September 16, 1998
• 年：1998
• 卷：120
• 期：36
• 页码：9228 - 9236
• 全文大小：344K
• 年卷期：v.120,no.36(September 16, 1998)
• ISSN：1520-5126

文摘

Alternaric acid, a nanomolar fungal germination inhibitor, is typified by a 1,4-diene, consisting ofa terminal methylene and an (E)-1,2-disubstituted alkene. A new strategy for the synthesis of natural productscontaining such functionality stems from the development of a ruthenium-catalyzed addition of terminal alkeneswith terminal alkynes. The alkyne substrate, 4-pentynoic acid, is commercially available or can be preparedin two steps by alkylation of tert-butyl acetate. The alkene substrate is prepared from commercially available(S)-2-methyl-1-butanol. This synthesis involves formation of a geometically defined trisubstituted alkene byinvolving Pd-catalyzed cross-coupling and asymmetric dihydroxylation. The ruthenium-catalyzed couplingproceeds best in the absence of alcohol protecting groups to maximize regioselectivity. The examples of thisaddition illustrated herein help elucidate some of the important factors controlling regioselectivity. They alsoillustrate the excellent chemoselectivity. The acyclic unit of alternaric acid, which is simply coupled to adihydropyrone fragment to complete the synthesis, is available in only 11 steps and 27% overall yield comparedto the one extant synthesis also starting from (S)-2-methyl-1-butanol which proceeds in 26 steps and 0.003%overall yield. This new reaction provides a powerful tool in streamlining this synthesis and should provemore generally useful.