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Concise Synthesis of Norrisolide
Author(s) -
Granger Krista,
Snapper Marc L.
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200134
Subject(s) - chemistry , cyclopropanation , total synthesis , enantioselective synthesis , cyclopentenone , electrophile , metathesis , side chain , furan , natural product , epoxide , silyl ether , stereoselectivity , silyl enol ether , combinatorial chemistry , stereochemistry , ring closing metathesis , claisen rearrangement , organic chemistry , enol , silylation , catalysis , polymer , polymerization
Abstract The marine natural product norrisolide has been synthesized in a convergent manner with a longest linear sequence of 14 steps. The hydrindane portion of the molecules is prepared through conjugate addition of a functionalized allyl group into cyclopentenone, followed by stereoselective trapping of the enolate generated from the resulting enol silyl ether with an allyl electrophile. Ring‐closing metathesis then establishes the 6–5 ring system. Likewise, selective preparation of the side chain features an enantioselective cyclopropanation of furan‐2‐one, followed by rearrangement and hydrogenation. Coupling of the two major fragments through a Shapiro reaction, followed by reduction and olefination then completes the carbon framework of the natural product. The final steps of the synthesis involve adjustments to the oxidation state of the side chain. New strategies to generate both the hydrindane core and the oxidized side chain has allowed for the more concise and efficient preparation of the natural product.