A Palladium-Catalyzed Oxa-(4+4)-Cycloaddition Strategy Towards Oxazocine Scaffolds

Abstract

A Pd-catalyzed oxa-(4+4)-cycloaddition between 1-azadienes and (2-hydroxymethyl)allyl carbonates is described. Aurone-derived azadienes furnished polycyclic 1,5-oxazocines in good yields. Interestingly, linear azadienes have also been involved and yielded monocyclic heterocycles with complete regioselectivity. DFT calculations were carried out to gain insight on this observation.

Key words

cycloaddition - catalysis - heterocycles - medium-sized rings - oxazocines - azadienes

Publication History

Received: 16 March 2021

Accepted after revision: 17 April 2021

Article published online:
19 May 2021

• References and Notes

• 1 Current address: Univ Rennes, CNRS ISCR-UMR 6226, 35000 Rennes, France.
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• 21 CCDC 2040269 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
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• 23 See the Supporting Information.
• 24 Typical Procedure for the Pd-Catalyzed (4+4) Cycloadditions of 2a with 1a (Benzene, rt) In a screw-cap SVL tube filled with argon, Pd₂(dba)₃ (13.7 mg, 0.015 mmol, 0.05 equiv) and dppe (12.0 mg, 0.03 mmol, 0.1 equiv) were added in benzene (3 mL, 0.1 M) and stirred for 15 min at rt. Carbonate 2a (84.7 mg, 0.45 mmol, 1.5 equiv) and azadiene 1a (113 mg, 0.30 mmol) were then added, the reaction mixture was stirred at rt for 16 h, filtered over silica, and concentrated under reduced pressure to afford the crude product. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc = 85:15) to afford 3a (109 mg, 81%) as a yellow solid; mp 46 °C. IR (neat): 2922, 1597, 1494, 1452, 1384, 1346, 1180, 1157, 1095, 1069, 747 cm^–1. ¹H NMR (400 MHz, CDCl₃, –20 °C): δ = 7.86 (d, J = 8.2 Hz, 2 H), 7.61–7.58 (m, 1 H), 7.41–7.12 (m, 10 H), 5.45 (s, 1 H), 5.24 (s, 1 H), 5.02 (s, 1 H), 4.91 (d, J = 13.5 Hz, 1 H), 4.58 (d, J = 12.6 Hz, 1 H), 4.24 (d, J = 12.6 Hz, 1 H), 4.10 (d, J = 13.5 Hz, 1 H), 2.44 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃, –20 °C): δ = 154.4, 153.0, 143.5, 139.3, 138.1, 136.4, 129.3 (2 C), 128.5, 128.4 (2 C), 127.8 (2 C), 127.6 (2 C), 126.6, 124.6, 123.1, 122.7, 120.0, 116.0, 111.3, 79.0, 75.9, 54.7, 21.6. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₂₆H₂₄NO₄S⁺: 446.1421; found: 446.1410.