A unified route to the welwitindolinone alkaloids: total syntheses of (-)-N-methylwelwitindolinone C isothiocyanate, (-)-N-methylwelwitindolinone C isonitrile, and (-)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate

doi:10.1021/ja210793x

. 2012 Jan 25;134(3):1392-5.

doi: 10.1021/ja210793x. Epub 2012 Jan 11.

A unified route to the welwitindolinone alkaloids: total syntheses of (-)-N-methylwelwitindolinone C isothiocyanate, (-)-N-methylwelwitindolinone C isonitrile, and (-)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate

Kevin M Allan¹, Kenichi Kobayashi, Viresh H Rawal

Affiliations

PMID: 22235963
PMCID: PMC3368435
DOI: 10.1021/ja210793x

A unified route to the welwitindolinone alkaloids: total syntheses of (-)-N-methylwelwitindolinone C isothiocyanate, (-)-N-methylwelwitindolinone C isonitrile, and (-)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate

Kevin M Allan et al. J Am Chem Soc. 2012.

. 2012 Jan 25;134(3):1392-5.

doi: 10.1021/ja210793x. Epub 2012 Jan 11.

Authors

Kevin M Allan¹, Kenichi Kobayashi, Viresh H Rawal

Affiliation

¹ Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, USA.

PMID: 22235963
PMCID: PMC3368435
DOI: 10.1021/ja210793x

Abstract

As part of a comprehensive strategy to the welwitindolinone alkaloids possessing a bicyclo[4.3.1]decane core, we report herein concise asymmetric total syntheses of (-)-N-methylwelwitindolinone C isothiocyanate (2a), (-)-N-methylwelwitindolinone C isonitrile (2b), and (-)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate (3a) from a common tetracyclic intermediate. The crucial vinyl chloride moiety was installed through electrophilic chlorination of a hydrazone, but only after adjustment of reactivity to circumvent a facile skeletal rearrangement. Selective desulfurization and oxidation of 2a provided access to 2b and 3a, respectively. Notably, this work provides corrected (1)H and (13)C NMR spectral data for 3a.

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Welwitindolinone alkaloids.

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1. Two elegant syntheses of the unique, cyclobutane-containing member of the family, welwitindolinone A isonitrile, have been reported:
2. Baran P. S.; Richter J. M. J. Am. Chem. Soc. 2005, 127, 15394. - PubMed
3. Reisman S. E.; Ready J. M.; Hasuoka A.; Smith C. J.; Wood J. L. J. Am. Chem. Soc. 2006, 128, 1448. - PubMed
1. Bhat V.; Allan K. M.; Rawal V. H. J. Am. Chem. Soc. 2011, 133, 5798. - PMC - PubMed
1. Bhat V.; Rawal V. H. Chem. Commun. 2011, 47, 9705. - PubMed

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[1] Stratmann K.; Moore R. E.; Bonjouklian R.; Deeter J. B.; Patterson G. M. L.; Shaffer S.; Smith C. D.; Smitka T. A. J. Am. Chem. Soc. 1994, 116, 9935.

Jimenez J. I.; Huber U.; Moore R. E.; Patterson G. M. L. J. Nat. Prod. 1999, 62, 569. - PubMed

[2] Stratmann K.; Moore R. E.; Bonjouklian R.; Deeter J. B.; Patterson G. M. L.; Shaffer S.; Smith C. D.; Smitka T. A. J. Am. Chem. Soc. 1994, 116, 9935.

[3] Jimenez J. I.; Huber U.; Moore R. E.; Patterson G. M. L. J. Nat. Prod. 1999, 62, 569. - PubMed

[4] Konopelski J. P.; Deng H.; Schiemann K.; Keane J. M.; Olmstead M. M. Synlett 1998, 1105.

Wood J. L.; Holubec A. A.; Stoltz B. M.; Weiss M. M.; Dixon J. A.; Doan B. D.; Shamji M. F.; Chen J. M.; Heffron T. P. J. Am. Chem. Soc. 1999, 121, 6326.

Deng H.; Konopelski J. P. Org. Lett. 2001, 3, 3001. - PubMed

Jung M. E.; Slowinski F. Tetrahedron Lett. 2001, 42, 6835.

López-Alvarado P.; García-Granda S.; Àlvarez-Rúa C.; Avendaño C. Eur. J. Org. Chem. 2002, 1702.

Ready J. M.; Reisman S. E.; Hirata M.; Weiss M. M.; Tamaki K.; Ovaska T. V.; Wood J. L. Angew. Chem., Int. Ed. 2004, 43, 1270. - PubMed

MacKay J. A.; Bishop R. L.; Rawal V. H. Org. Lett. 2005, 7, 3421. - PubMed

Baudoux J.; Blake A. J.; Simpkins N. S. Org. Lett. 2005, 7, 4087. - PubMed

Greshock T. J.; Funk R. L. Org. Lett. 2006, 8, 2643. - PMC - PubMed

Lauchli R.; Shea K. J. Org. Lett. 2006, 8, 5287. - PubMed

Xia J.; Brown L. E.; Konopelski J. P. J. Org. Chem. 2007, 72, 6885. - PMC - PubMed

Richter J. M.; Ishihara Y.; Masuda T.; Whitefield B. W.; Llamas T.; Pohjakallio A.; Baran P. S. J. Am. Chem. Soc. 2008, 130, 17938. - PMC - PubMed

Boissel V.; Simpkins N. S.; Bhalay G.; Blake A. J.; Lewis W. Chem. Commun. 2009, 1398. - PubMed

Boissel V.; Simpkins N. S.; Bhalay G. Tetrahedron Lett. 2009, 50, 3283.

Tian X.; Huters A. D.; Douglas C. J.; Garg N. K. Org. Lett. 2009, 11, 2349. - PubMed

Trost B. M.; McDougall P. J. Org. Lett. 2009, 11, 3782. - PMC - PubMed

Brailsford J. A.; Lauchli R.; Shea K. J. Org. Lett. 2009, 11, 5330. - PMC - PubMed

Freeman D. B.; et al. Tetrahedron 2010, 66, 6647. - PMC - PubMed

Heidebrecht R. W. Jr.; Gulledge B.; Martin S. F. Org. Lett. 2010, 12, 2492. - PMC - PubMed

Ruiz M.; López-Alvarado P.; Menéndez J. C. Org. Biomol. Chem. 2010, 8, 4521. - PubMed

Bhat V.; MacKay J. A.; Rawal V. H. Org. Lett. 2011, 13, 3214. - PMC - PubMed

Bhat V.; MacKay J. A.; Rawal V. H. Tetrahedron 2011, 67, 10097. - PMC - PubMed

[5] Konopelski J. P.; Deng H.; Schiemann K.; Keane J. M.; Olmstead M. M. Synlett 1998, 1105.

[6] Wood J. L.; Holubec A. A.; Stoltz B. M.; Weiss M. M.; Dixon J. A.; Doan B. D.; Shamji M. F.; Chen J. M.; Heffron T. P. J. Am. Chem. Soc. 1999, 121, 6326.

[7] Deng H.; Konopelski J. P. Org. Lett. 2001, 3, 3001. - PubMed

[8] Jung M. E.; Slowinski F. Tetrahedron Lett. 2001, 42, 6835.

[9] López-Alvarado P.; García-Granda S.; Àlvarez-Rúa C.; Avendaño C. Eur. J. Org. Chem. 2002, 1702.

[10] Ready J. M.; Reisman S. E.; Hirata M.; Weiss M. M.; Tamaki K.; Ovaska T. V.; Wood J. L. Angew. Chem., Int. Ed. 2004, 43, 1270. - PubMed

[11] MacKay J. A.; Bishop R. L.; Rawal V. H. Org. Lett. 2005, 7, 3421. - PubMed

[12] Baudoux J.; Blake A. J.; Simpkins N. S. Org. Lett. 2005, 7, 4087. - PubMed

[13] Greshock T. J.; Funk R. L. Org. Lett. 2006, 8, 2643. - PMC - PubMed

[14] Lauchli R.; Shea K. J. Org. Lett. 2006, 8, 5287. - PubMed

[15] Xia J.; Brown L. E.; Konopelski J. P. J. Org. Chem. 2007, 72, 6885. - PMC - PubMed

[16] Richter J. M.; Ishihara Y.; Masuda T.; Whitefield B. W.; Llamas T.; Pohjakallio A.; Baran P. S. J. Am. Chem. Soc. 2008, 130, 17938. - PMC - PubMed

[17] Boissel V.; Simpkins N. S.; Bhalay G.; Blake A. J.; Lewis W. Chem. Commun. 2009, 1398. - PubMed

[18] Boissel V.; Simpkins N. S.; Bhalay G. Tetrahedron Lett. 2009, 50, 3283.

[19] Tian X.; Huters A. D.; Douglas C. J.; Garg N. K. Org. Lett. 2009, 11, 2349. - PubMed

[20] Trost B. M.; McDougall P. J. Org. Lett. 2009, 11, 3782. - PMC - PubMed

[21] Brailsford J. A.; Lauchli R.; Shea K. J. Org. Lett. 2009, 11, 5330. - PMC - PubMed

[22] Freeman D. B.; et al. Tetrahedron 2010, 66, 6647. - PMC - PubMed

[23] Heidebrecht R. W. Jr.; Gulledge B.; Martin S. F. Org. Lett. 2010, 12, 2492. - PMC - PubMed

[24] Ruiz M.; López-Alvarado P.; Menéndez J. C. Org. Biomol. Chem. 2010, 8, 4521. - PubMed

[25] Bhat V.; MacKay J. A.; Rawal V. H. Org. Lett. 2011, 13, 3214. - PMC - PubMed

[26] Bhat V.; MacKay J. A.; Rawal V. H. Tetrahedron 2011, 67, 10097. - PMC - PubMed

[27] Two elegant syntheses of the unique, cyclobutane-containing member of the family, welwitindolinone A isonitrile, have been reported:

Baran P. S.; Richter J. M. J. Am. Chem. Soc. 2005, 127, 15394. - PubMed

Reisman S. E.; Ready J. M.; Hasuoka A.; Smith C. J.; Wood J. L. J. Am. Chem. Soc. 2006, 128, 1448. - PubMed

[28] Two elegant syntheses of the unique, cyclobutane-containing member of the family, welwitindolinone A isonitrile, have been reported:

[29] Baran P. S.; Richter J. M. J. Am. Chem. Soc. 2005, 127, 15394. - PubMed

[30] Reisman S. E.; Ready J. M.; Hasuoka A.; Smith C. J.; Wood J. L. J. Am. Chem. Soc. 2006, 128, 1448. - PubMed

[31] Bhat V.; Allan K. M.; Rawal V. H. J. Am. Chem. Soc. 2011, 133, 5798. - PMC - PubMed

[32] Bhat V.; Allan K. M.; Rawal V. H. J. Am. Chem. Soc. 2011, 133, 5798. - PMC - PubMed

[33] Bhat V.; Rawal V. H. Chem. Commun. 2011, 47, 9705. - PubMed

[34] Bhat V.; Rawal V. H. Chem. Commun. 2011, 47, 9705. - PubMed

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A unified route to the welwitindolinone alkaloids: total syntheses of (-)-N-methylwelwitindolinone C isothiocyanate, (-)-N-methylwelwitindolinone C isonitrile, and (-)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate

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A unified route to the welwitindolinone alkaloids: total syntheses of (-)-N-methylwelwitindolinone C isothiocyanate, (-)-N-methylwelwitindolinone C isonitrile, and (-)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate

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