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Regioselectivity of the Claisen Rearrangement in meta ‐Allyloxy Aryl Ketones: An Experimental and Computational Study, and Application in the Synthesis of ( R )‐(−)‐Pestalotheol D
Author(s) -
Lucas Catherine L.,
Lygo Barry,
Blake Alexander J.,
Lewis William,
Moody Christopher J.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201002757
Subject(s) - regioselectivity , claisen rearrangement , carroll rearrangement , chemistry , ketone , steric effects , aryl , sigmatropic reaction , silyl enol ether , ether , stereochemistry , enol , electronic effect , medicinal chemistry , organic chemistry , catalysis , alkyl
A study of the regioselectivity of the Claisen rearrangement of meta ‐allyloxy aryl ketones showed that the electron‐withdrawing carbonyl group has a major influence and strongly directs rearrangement to the more hindered ortho position. However, when the ketone is part of a ring structure, its electronic effect can be negated by conversion into its triisopropylsilyl enol ether, which dramatically reverses the regiochemistry of the Claisen rearrangement. DFT calculations suggest that the effect is electronic although there is also a steric effect of the bulky silyl group. This strategy for influencing the regiochemical outcome of the Claisen rearrangement was then employed in a short synthesis of the furo[2,3‐ g ]chromene, (−)‐pestalotheol D, that confirms the absolute stereochemistry of the natural product.