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Synlett 2002(3): 0411-0414
DOI: 10.1055/s-2002-20453
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Practical Variant of the Claisen-Eschenmoser Rearrangement: Synthesis of Unsaturated Morpholine Amides

Stefan N. Gradl, Joshua J. Kennedy-Smith, James Kim, Dirk Trauner*
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, CA 94720-1460, USA
Fax: +1(510)6439480; e-Mail: trauner@cchem.berkeley.edu;
Further Information

Publication History

Received 10 December 2001
Publication Date:
05 February 2007 (online)

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Abstract

A Claisen-Eschenmoser type rearrangement giving rise to unsaturated morpholine-, piperidine- and pyrrolidine amides is described.

Key words

Claisen-Eschenmoser rearrangement - morpholine amides - ketene N,N-acetal - guanacastepene - ring closing metathesis

    References

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7

Representative Procedure, Morpholine Amide 4f: A round-bottomed flask was charged with 8 mL morpholine (80 mmol) and dimethylacetamide dimethyl acetal (3.8 mL, 30 mmol) and the mixture was slowly heated to 190 °C over 5 hours under a steady stream of N2. After cooling to room temperature, xylenes (10 mL) and 2,4-dimethyl-penta-2,4-dien-1-ol (1.32 g, 11.7 mmol) were added and the reaction mixture was refluxed until the allylic alcohol was consumed (14 hours) as determined by TLC (30% hexanes in ethylacetate, v/v). The solvent was partially removed using a rotary evaporator. The residue was purified by column chromatography (hexanes → ethyl acetate:hexanes = 1:1) to afford the pure product as a colorless oil (1.95 g, 8.74 mmol, 74.3%). 1H NMR (500 MHz, CDCl3) δ 4.84 (s, 2 H), 4.73 (s, 2 H), 3.63 (m, 6 H), 3.47 (m, 2 H), 3.21 (t, J = 9 Hz, 1 H), 2.54 (d, J = 9 Hz, 2 H), 1.66 (s, 6 H). 13C NMR (125MHz, CDCl3) δ 170.3, 145.5, 111.2, 66.9, 66.7, 49.9, 46.1, 42.0, 34.6, 20.8. IR(neat) 3077, 2966, 2855, 1650, 1643, 1432, 1271, 1234, 1115, 1034 cm-1. MS (EI) m/z 223(23), 129(42), 114(42), 109(17), 95(100). HRMS (EI) m/z calcd for C13H21NO2: 223.1572, found: 223.1570.

9

Details of the crystal structure determination (deposition number CCDC 165896) may be obtained from: The Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1 EZ, UK.

11

An analogous reaction involving Z-2-hexenol(4b) gave a 13:1 mixture of diastereomers. Their relative configurations, however, were not assigned.

16

Yields were much higher (70%) when the corresponding Weinreb amide was used.