Radical Cyclization of Olefinic Amides through α-C(sp³)–H Functionalization of Ketones under Catalyst-, Ligand-, and Base-Free Conditions

Abstract

A new, efficient, and practical radical cyclization of olefinic amides with ketones through α-C(sp³)–H functionalization in the presence of tert-butyl peroxybenzoate (TBPB) is described for the first time. This protocol assembles a wide range of pivotal and useful benzoxazines in good to excellent yields under mild, catalyst-free, ligand-free, and base-free conditions with wide functional group tolerance. Moreover, the mechanistic study indicates that the α-carbonyl radical is involved in this transformation.

Key words

green synthesis - catalyst-free - ligand-free - base-free - radical cyclization - α-C(sp³)–H functionalization

Publication History

Received: 21 January 2021

Accepted after revision: 27 March 2021

Accepted Manuscript online:
27 March 2021

Article published online:
16 April 2021

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• 11 General Procedure To a Schlenk tube were added olefinic amides 1 (0.2 mmol), ketones 2 (1.0 mL), and TBPB (2.0 equiv). Then the tube was stirred at 120 °C sealed in air for the indicated time until complete consumption of starting material as monitored by TLC and/or GC–MS analysis. After the reaction was finished, the solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography over silica gel (hexane/ethyl acetate = 10:1) to afford the desired product 3 and was analyzed by ¹H NMR and ¹³C NMR spectroscopy (see the Supporting Information). Typical Data for Representative Compound 4-(4-Methyl-2-phenyl-4H-benzo[d][1,3]oxazin-4-yl)butan-2-one (3aa) Yellow oil (0.0500 g, 85% yield). ¹H NMR (500 MHz, CDCl₃): δ = 8.13–8.12 (m, 2 H), 7.52–7.49 (m, 1 H), 7.46–7.43 (m, 2 H), 7.31–7.30 (m, 2 H), 7.21–7.18 (m, 1 H), 7.07 (d, J = 7.5 Hz, 1 H), 2.66–2.59 (m, 1 H), 2.48–2.42 (m, 1 H), 2.39–2.31 (m, 2 H), 2.05 (s, 3 H), 1.67 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 207.8, 156.4, 139.1, 132.8, 131.4, 128.7 (2),128.3, 127.8, 126.8, 125.5, 122.7, 80.4, 38.4, 35.0, 30.1, 28.7.
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