Abstract
The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er).
Highlights
Quinone methides (QMs) are electrophilic compounds composed of a cyclohexadiene core bearing a carbonyl either ortho or para to an exocyclic alkylidene unit [1,2]
Initial studies focused on the isothiourea-catalyzed 1,6-conjugate addition of paranitrophenyl (PNP) ester 1 to 2,6-di-tert-butyl para-QM 5 (Table 1)
Variation of the arylacetic ester and para-QM substrates has provided a range of functionalized products in generally excellent yields and high enantiocontrol
Summary
Quinone methides (QMs) are electrophilic compounds composed of a cyclohexadiene core bearing a carbonyl either ortho or para to an exocyclic alkylidene unit [1,2]. C(1)-Ammonium enolate intermediates [52,53,54,55], generated by the reaction of a tertiary amine Lewis base catalyst with a ketene, anhydride or acyl imidazole [56], have found widespread application for the synthesis of heterocyclic scaffolds in high yield and with excellent enantiocontrol. These approaches have been limited by the requirement for the electrophilic reaction partner to contain a latent nucleophilic site to facilitate catalyst turnover.
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