Open AccessToward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids
Author(s) -
Scott E. Denmark,
Pavel Ryabchuk,
Matthew T. Burk,
Bradley B. Gilbert
Publication year - 2016
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.6b01455
Subject(s) - chemistry , enantioselective synthesis , lewis acids and bases , nucleophile , catalysis , carboxylate , hydrogen bond , combinatorial chemistry , organocatalysis , organic chemistry , molecule
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.