Zn(OTf)₂-Catalyzed 1,6-Conjugate Addition of Benzoxazinones to p-Quinone Methides: Access to 3,3-Diaryl-2-(2-oxo-2H-1,4-benzoxazin-3-yl)propanoic Acid Esters

Abstract

An effective method for the synthesis of 3,3-diaryl-2-(2-oxo-2H-1,4-benzoxazin-3-yl)propanoic acid esters is reported. A novel zinc triflate-catalyzed regioselective 1,6-conjugate addition of vinylogous carbamates to p-quinone methides for accessing the title compounds has been developed. This protocol furnished the hybrid compounds in good to excellent yields. The reaction is rapid and has a broad substrate scope.

Key words

para-quinone methides - vinylogous carbamates - 1,6-addition - regioselectivity - diastereoselectivity - benzoxazines

Publication History

Received: 10 August 2020

Accepted after revision: 20 October 2020

Article published online:
19 January 2021

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• 28 3,3-Diaryl-2-(2-oxo-2H-1,4-benzoxazin-3-yl)propanoate Esters 3–21: General Procedure The appropriate benzoxazine 2 (0.5 mmol) was added to a stirred solution of the appropriate p-QM derivative 1 (0.6 mmol) in MeCN (3 mL), and the mixture was stirred at rt. Zn(OTf)₂ (2 mol%) was added, and the mixture was stirred at rt until the reaction was complete (TLC). The crude mixture analyzed by ¹H NMR to determine the dr of the diastereomers, then purified by chromatography on a short column [silica gel (100–200 mesh), EtOAc–hexanes (5:95)]. Methyl 3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-2-(2-oxo-2H-1,4-benzoxazin-3-yl)-3-phenylpropanoate (3) Reaction time: 5 min. White solid; yield: 5 mg (93%); mp 146.4–147.6 °C (mixture of diastereomers). ¹H NMR (400 MHz, CDCl₃): δ = 7.78 (d, J = 8.0 Hz, 1 H), 7.49 (d, J = 8.0 Hz, 2 H), 7.43 (t, J = 8.0 Hz, 2 H), 7.34–7.28 (m, 4 H), 7.23–7.13 (m, 4 H), 7.04 (t, J = 8.0 Hz, 1 H), 6.96 (s, 2 H), 5.29 (d, J = 4.0 Hz, 1 H), 5.25 (d, J = 4.0 Hz, 1 H), 5.07–5.02 (m, 1 H), 4.93 (d, J = 12.0 Hz, 1 H), 4.91 (s, 1 H, OH), 3.56 (s, 3 H), 3.47 (s, 1 H), 1.41 (s, 7 H), 1.21 (s, 18 H). ¹³C NMR (100 MHz, CDCl₃): δ = 170.1, 170.0, 154.2, 152.4, 152.1, 146.1, 142.6, 135.8, 135.7, 131.3, 131.2, 131.1, 129.3, 128.6, 127.8, 125.5, 116.3, 52.6, 34.4, 34.2, 30.4, 30.1. HRMS (ESI-TOF): m/z [M + Na] ⁺ calcd for C₃₂H₃₅NNaO₅: 536.2407; found: 536.2408.