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Synlett 2003(14): 2131-2134  
DOI: 10.1055/s-2003-42068
LETTER
© Georg Thieme Verlag Stuttgart · New York

N-Bromosuccinimide Promoted Ring Expansion Reactions: Diastereoselective Formation of Functionalized Azaspirocyclic Cyclopentanones

Paul B. Hurley, Gregory R. Dake*
Department of Chemistry, 2036 Main Mall, The University of British Columbia, Vancouver, B.C., V6T 1Z1, Canada
Fax: +1(604)8222847; e-Mail: gdake@chem.ubc.ca;
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Publication History

Received 20 May 2003
Publication Date:
07 October 2003 (online)

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Abstract

N-Bromosuccinimide (NBS) induces ring enlargements of 2-(1-hydroxycyclobutyl)-p-toluenesulfonylenamides such as 1. These high yielding reactions typically occur with good diastereoselectivity. This ring expansion protocol under neutral conditions forms compounds that are potentially versatile intermediates for the construction of spirocycle-containing alkaloids.

Key words

bromine - ring expansion - stereoselective - piperidines - spiro compounds

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All new compounds have been satisfactorily characterized spectroscopically (IR, 1H NMR, 13C NMR, MS).

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A representative experimental procedure for the NBS-promoted ring expansion reaction: (5 S * ,7 S *,10 S *)-10-Bromo-7-ethoxy-6-[(4-methylphenyl)sulfonyl]-6-azaspiro[4.5]decan-1-one ( 3): To a stirred solution of cyclobutanol 1 (100 mg, 0.285 mmol, 1 equiv) in propylene oxide (2 mL) and i-PrOH (2 mL) at -78 °C was added N-bromosuccinimide (60.8 mg, 0.341 mmol). The mixture was stirred at -78 °C for 2 h. The reaction was warmed to r.t. over 1 h and solvents were removed in vacuo. Column chromatography on silica gel (10% EtOAc-hexanes) gave 117 mg (96%) of a white solid; mp 100-103 °C(dec). IR (KBr): 2938, 1740, 1328, 1137 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.5 Hz, 2 H), 7.29 (d, J = 8.2 Hz, 2 H), 4.87 (dd, J = 5.2, 1.5 Hz, 1 H), 4.61 (dd, J = 11.6, 4.3 Hz, 1 H), 3.89 (dq, J = 9.8, 7.0 Hz, 1 H), 3.52 (dq, J = 9.8, 7.0 Hz, 1 H), 2.78 (dt, J = 14.0, 9.5 Hz, 1 H), 2.70 (ddd, J = 19.2, 10.4, 8.9 Hz, 1 H), 2.55-2.29 (m, 3 H), 2.42 (s, 3 H), 2.26-2.01 (m, 3 H), 1.86-1.68 (m, 2 H), 1.19 (t, J = 7.0 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 214.2, 143.6, 138.1, 129.4, 127.5, 83.4, 68.2, 63.7, 50.8, 40.3, 37.4, 28.6, 25.3, 21.5, 18.4, 15.2; MS (ESI): m/z 424 [M + 2 - EtOH + K]+, 422 [M - EtOH + K]+, 408 [M + 2 - EtOH + Na]+, 406 [M - EtOH + Na]+, 386(47), 384(45).