Issue 2, 2017

Stereodivergent, Diels–Alder-initiated organocascades employing α,β-unsaturated acylammonium salts: scope, mechanism, and application

Abstract

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.

Graphical abstract: Stereodivergent, Diels–Alder-initiated organocascades employing α,β-unsaturated acylammonium salts: scope, mechanism, and application

Supplementary files

Article information

Article type
Edge Article
Submitted
23 Sep 2016
Accepted
24 Oct 2016
First published
25 Oct 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 1511-1524

Stereodivergent, Diels–Alder-initiated organocascades employing α,β-unsaturated acylammonium salts: scope, mechanism, and application

M. E. Abbasov, B. M. Hudson, D. J. Tantillo and D. Romo, Chem. Sci., 2017, 8, 1511 DOI: 10.1039/C6SC04273B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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