Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids

Scott E. Denmark, Pavel Ryabchuk, Matthew T. Burk, Bradley B. Gilbert

Research output: Contribution to journalArticle

Abstract

An investigation into the use of Lewis base catalysis for the enantioselective chlorolactonization of 1,2-disubstituted alkenoic acids is described. Two mechanistically distinct reaction pathways for catalytic chlorolactonization have been identified. Mechanistic investigation revealed that tertiary amines predominately operate as Brønsted rather than Lewis bases. Two potential modes of activation have been identified that involve donation of electron density of the carboxylate to the C=C bond as well hydrogen bonding to the chlorinating agent. Sulfur- and selenium-based additives operate under Lewis base catalysis; however, due to the instability of the intermediate benzylic chloriranium ion, chlorolactonization suffers from low chemo-, diastereo-, and enantioselectivities. Independent generation of the benzylic chloriranium ion shows that it is in equilibrium with an open cation, which leads to low specificities in the nucleophilic capture of the intermediate.

Original languageEnglish (US)
Pages (from-to)10411-10423
Number of pages13
JournalJournal of Organic Chemistry
Volume81
Issue number21
DOIs
StatePublished - Nov 4 2016

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Lewis Bases
Carboxylic Acids
Catalysis
Ions
Enantioselectivity
Chemical bonds
Selenium
Carboxylic acids
Sulfur
Amines
Carrier concentration
Cations
Hydrogen bonds
Chemical activation

ASJC Scopus subject areas

  • Organic Chemistry

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Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids. / Denmark, Scott E.; Ryabchuk, Pavel; Burk, Matthew T.; Gilbert, Bradley B.

In: Journal of Organic Chemistry, Vol. 81, No. 21, 04.11.2016, p. 10411-10423.

Research output: Contribution to journalArticle

Denmark, Scott E. ; Ryabchuk, Pavel ; Burk, Matthew T. ; Gilbert, Bradley B. / Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids. In: Journal of Organic Chemistry. 2016 ; Vol. 81, No. 21. pp. 10411-10423.
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