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Synlett 2011(6): 801-804  
DOI: 10.1055/s-0030-1259918
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A New Strategy for the Synthesis of Himbacine

Mike Casey*, Robert McCarthy
School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland
Fax: +353(1)7181178; e-Mail: mike.casey@ucd.ie;
Further Information

Publication History

Received 7 February 2011
Publication Date:
16 March 2011 (online)

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Abstract

A new strategy for the assembly of himbacine and analogues, which display potent biological activity, is described. A four-step route to a key intermediate has been developed, in which the key step is a highly diastereoselective Michael-Dieckmann domino reaction. Use of an enantioenriched Michael acceptor, readily obtained by an asymmetric dihydroxylation reaction, allowed kinetic resolution of the Michael donor, which was itself prepared by a domino reaction.

Key words

alkaloids - domino reactions - kinetic resolution - Michael additions - stereoselective synthesis

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16

Data for compound 22: white solid; mp 144-146 ˚C; [α]D ²³ -6.0 (c = 0.85, CHCl3). IR (KBr): 2980, 2924, 2831, 1780, 1719, 1702, 1408, 1334, 1280, 1210, 1160, 1012 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 4.27 (1 H, dq, J = 10.3, 5.9 Hz, C³H), 3.80 (1 H, d, J = 8.6 Hz, C9aH), 2.66-2.77 (2 H, m, C8aH, C³aH), 2.54 (1 H, app d, J = 4.6 Hz, C4H), 2.03
(1 H, m, C8HH), 1.77-1.87 (4 H, m, C4aH, C5HH, C6HH, C7HH), 1.54 [9 H, s, C(CH3)3], 1.45 (3 H, d, J = 5.9 Hz, C³HCH 3), 1.34-1.40 (1 H, m, C5 HH), 1.26-1.34 (1 H, m, C8 HH), 1.15-1.26 (2 H, m, C6 HH, C7 HH). ¹³C NMR (125 MHz, CDCl3): δ = 203.7 (C9=O), 171.9 (OC=O), 170.9 (OC=O), 82.4 [C(CH3)3], 77.5 (C³H), 54.4 (C9aH), 48.3 (C³aH), 48.0 (C8aH), 44.1 (C4H), 41.0 (C4aH), 31.3 (C5H2), 28.2 [C(CH3)3], 25.6 (C7H2), 25.4 (C8H2), 25.0 (C6H2), 19.0 [C³H(CH3)]. HRMS (ESI): m/z [M+ + H] calcd for C18H27O5: 323.1858; found: 323.1847.

17

CCDC 711490 contains the crystallographic data for compound 22. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallograpic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033; or deposit@ccdc.cam.ac.uk].