We are grateful to Dr. W. B. Schweizer for the X-ray crystallographic analysis, and to Dr. M.-O. Ebert, R. Frankenstein, P. Zumbrunnen, and R. Arnold for NMR spectroscopic studies.
1521-3773/asset/2002_left.gif?v=1&s=ac6b0d94a94d7ce7a210002b8096b42feffc0bcf)
1521-3773/asset/2002_right.gif?v=1&s=451042aa3415ae3ad0729984d26dee1866aca82e)
Communication
You have free access to this content
Total Synthesis of (+)-Daphmanidin E†
Article first published online: 11 OCT 2011
DOI: 10.1002/anie.201104681
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Issue
Angewandte Chemie International Edition
Volume 50, Issue 48, pages 11501–11505, November 25, 2011
Additional Information
How to Cite
Weiss, M. E. and Carreira, E. M. (2011), Total Synthesis of (+)-Daphmanidin E. Angew. Chem. Int. Ed., 50: 11501–11505. doi: 10.1002/anie.201104681
- †
Publication History
- Issue published online: 18 NOV 2011
- Article first published online: 11 OCT 2011
- Manuscript Received: 6 JUL 2011
- 1, , Nat. Prod. Rep. 2009, 26, 936–963, and references therein.
- 2For recent studies not covered Ref. [1], see , , , , Org. Lett. 2009, 11, 1833–1836; , , , , , Org. Lett. 2009, 11, 5658–5661; , , , , Org. Lett. 2011, 13, 1267–1269.
- 3
- 4aThe resolution via diastereomeric hydrazones is detailed in the Supporting Information;
- 4bfor a recently published, chemoenzymatic procedure, see , , Angew. Chem. 2010, 122, 2810–2814; Angew. Chem. Int. Ed. 2010, 49, 2750–2754;
- 4cit is possible to selectively generate the monoenolate of 3 with 1 equiv of KN(SiMe3)2. However, inspection of molecular models indicated that olefinic ketone 6′, which would be generated a few steps later, would expose the undesired olefin face in its subsequent hydroboration.
- 5
- 6
- 7, , , Angew. Chem. 2001, 113, 4676–4701;Angew. Chem. Int. Ed. 2001, 40, 4544–4568.Direct Link:Direct Link:
- 8For hydroboration of a trisubstituted olefin embedded in a bicyclo[2.2.2]octane system, see , , , , J. Org. Chem. 1987, 52, 2509–2517.
- 9
- 10CCDC 832940 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
- 11
- 12The preferred formation of compound 11 in the Claisen rearrangement was rationalized by comparison of the four possible transition states. Two could be immediately excluded because they would require a superposition of the cyclopentene residue and a bridge of the bicyclo[2.2.2]octane. Unfavorable steric interactions of the cyclopentene residue with the substituent at C(6) and CH2OBz group at the bridgehead are expected to arise in TS1, whereas these destabilizing interactions would be absent in TS2.
- 13, , , J. Org. Chem. 1976, 41, 1485–1486; , , J. Org. Chem. 1975, 40, 947–949.
- 14
- 15The hydroxy groups were differentiated by the following sequence: 1) Me3Si/imidazole, CH2Cl2, RT→protects primary alcohol. Then MOMCl, iPr2NEt, CH2Cl2, RT→protects secondary alcohol. Then TBAF, THF, RT→removes SiMe3 from primary alcohol.
- 16
- 17
- 18For examples, see
- 18a
- 18b
- 18c
- 19
- 20The relative configuration at C(18) was established by NOESY experiments on a more advanced, cyclic imine.
- 21For examples, see
- 21a
- 21b
- 21c
- 22
- 22a
- 22b, , , Angew. Chem. 2009, 121, 7276–7301;Angew. Chem. Int. Ed. 2009, 48, 7140–7165;Direct Link:Direct Link:
- 22c
- 22d
- 22e
- 23For selected examples, see
- 23a
- 23b
- 23c
- 23d, , , , , , , J. Am. Chem. Soc. 2005, 127, 14911–14921;
- 23e
- 24
- 24a
- 24b
- 25For selected examples of cobalt-mediated alkyl-Heck coupling reactions, see
- 25a
- 25b
- 25c, , J. Chem. Soc. Chem. Commun. 1987, 166–168. For a review, see , Rev. Heteroat. Chem. 1999, 20, 97–144.
- 26
- 27
- 28Significant differences in the 1H NMR spectrum were observed if a sample of the iminium salt was dried under high vacuum before the measurement. Titration with incremental amounts of TFA showed that the chemical shifts in the 1H NMR spectrum of 1 change significantly with an increasing degree of imine protonation.
- 29A significant deviation in the magnitude of the optical rotation of synthetic 1 and the reported value was noted. This discrepancy could not be explained, but was tentatively attributed to the unknown purity and degree of protonation of a sample of 1 isolated from natural sources.