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  • Stereodivergent, Diels–Alder-initiated organocascades employing α,β-unsaturated acylammonium salts: scope, mechanism, and application
Title: Stereodivergent, Diels–Alder-initiated organocascades employing α,β-unsaturated acylammonium salts: scope, mechanism, and application
Chiral α,β-unsaturated acylammonium salts are novel dienophiles enabling enantioselective Diels–Alder-lactonization (DAL) organocascades leading to cis - and trans -fused, bicyclic γ- and δ-lactones from readily prepared dienes, commodity acid chlorides, and a chiral isothiourea organocatalyst under mild conditions. We describe extensions of stereodivergent DAL organocascades to other racemic dienes bearing pendant secondary and tertiary alcohols, and application to a formal synthesis of (+)-dihydrocompactin is described. A combined experimental and computational investigation of unsaturated acylammonium salt formation and the entire DAL organocascade pathway provide a rationalization of the effect of Brønsted base additives and enabled a controllable, diastereodivergent DAL process leading to a full complement of possible stereoisomeric products. Evaluation of free energy and enthalpy barriers in conjunction with experimentally observed temperature effects revealed that the DAL is a rare case of an entropy-controlled diastereoselective process. NMR analysis of diene alcohol–Brønsted base interactions and computational studies provide a plausible explanation of observed stabilization of exo transition-state structures through hydrogen-bonding effects.  more » « less
Award ID(s):
1800411
NSF-PAR ID:
10296737
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Chemical Science
Volume:
8
Issue:
2
ISSN:
2041-6520
Page Range / eLocation ID:
1511 to 1524
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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