Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec 30;67(52):100997-10104.
doi: 10.1016/j.tet.2011.09.088. Epub 2011 Sep 24.

Lessons Learned while Traversing the Welwitindolinone Alkaloids Obstacle Course

Vikram Bhat  1 , James A Mackay, Viresh H Rawal
Affiliations

Lessons Learned while Traversing the Welwitindolinone Alkaloids Obstacle Course

Vikram Bhat et al. Tetrahedron. .

Abstract

We recount several unexpected results observed in the course of our work toward the synthesis of welwitindolinone alkaloids. The surprising results provide an opportunity to refine one's understanding of the interplay between chemical structure and reactivity.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Representative Welwitindolinone Alkaloids
Figure 2
Figure 2
ORTEP Image of 36
Scheme 1
Scheme 1
Vilsmeier–Haack Deconjugative Methylation Approach
Scheme 2
Scheme 2
Vilsmeier–Haack Chloroformylation of Dione 5
Scheme 3
Scheme 3
Attempts to Functionalize the C12-Position of Dione 5
Scheme 4
Scheme 4
Formation of the Decarboxylated Welwitindolinone
Scheme 5
Scheme 5
Successful Synthesis of the Functionalized Welwitindolinone Core
Scheme 6
Scheme 6
Unexpected Rearrangement during Deoxygenative Chlorination
Scheme 7
Scheme 7
Unanticipated Intramolecular Reaction
Scheme 8
Scheme 8
Attempts to Synthesize the Alkenyl Chloride
Scheme 9
Scheme 9
Plausible Mechanism for the Unusual Rearrangement
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. MacKay JA, Bishop RL, Rawal VH. Org Lett. 2005;7:3421–3424. - PubMed
    2. Bhat V, Allan KM, Rawal VH. J Am Chem Soc. 2011;133:5798–5801. - PMC - PubMed
    3. Bhat V, MacKay JA, Rawal VH. Org Lett. 2011;13:3214–3217. - PMC - PubMed
    4. Bhat V, Rawal VH. Chem Commun. 2011;47:9705–9707. - PubMed
    1. Stratmann K, Moore RE, Bonjouklian R, Deeter JB, Patterson GMLS, Shaffer Smith CD, Smitka TA. J Am Chem Soc. 1994;116:9935–9942.
    2. Jimenez JI, Huber U, Moore RE, Patterson GML. J Nat Prod. 1999;62:569–572. - PubMed

    1. For approaches toward the welwitindolinones (1–3), see: Konopelski JP, Deng H, Schiemann K, Keane JM, Olmstead MM. Synlett. 1998:1105–1107.Wood JL, Holubec AA, Stoltz BM, Weiss MM, Dixon JA, Doan BD, Shamji MF, Chen JM, Heffron TP. J Am Chem Soc. 1999;121:6326–6327.Kaoudi T, Ouiclet-Sire B, Seguin S, Zard SZ. Angew Chem, Int Ed. 2000;39:731–733.Deng H, Konopelski JP. Org Lett. 2001;3:3001–3004.Jung ME, Slowinski F. Tetrahedron Lett. 2001;42:6835–6838.López-Alvarado P, García-Granda S, Àlvarez-Rúa C, Avendaño C. Eur J Org Chem. 2002:1702–1707.Ready JM, Reisman SE, Hirata M, Weiss MM, Tamaki K, Ovaska TV, Wood JL. Angew Chem, Int Ed. 2004;43:1270–1272.Baudoux J, Blake AJ, Simpkins NS. Org Lett. 2005;7:4087–4089.Greshock TJ, Funk RL. Org Lett. 2006;8:2643–2645.Lauchli R, Shea KJ. Org Lett. 2006;8:5287–5289.Xia J, Brown LE, Konopelski JP. J Org Chem. 2007;72:6885–6890.Richter JM, Ishihara Y, Masuda T, Whitefield BW, Llamas T, Pohjakallio A, Baran PS. J Am Chem Soc. 2008;130:17938–17954.Boissel V, Simpkins NS, Bhalay G, Blake AJ, Lewis W. Chem Commun. 2009:1398–1400.Boissel V, Simpkins NS, Bhalay G. Tetrahedron Lett. 2009;50:3283–3286.Tian X, Huters AD, Douglas CJ, Garg NK. Org Lett. 2009;11:2349–2351.Trost BM, McDougall PJ. Org Lett. 2009;11:3782–3785.Brailsford JA, Lauchli R, Shea KJ. Org Lett. 2009;11:5330–5333.Freeman DB, et al. Tetrahedron. 2010;66:6647–6655.Heidebrecht RW, Jr, Gulledge B, Martin SF. Org Lett. 2010;12:2492–2495.Ruiz M, López-Alvarado P, Menéndez JC. Org Biomol Chem. 2010;8:4521–4523.

    1. Total syntheses of welwitindolinone A: Baran PS, Richter JM. J Am Chem Soc. 2005;127:15394–15396.Reisman SE, Ready JM, Hasuoka A, Smith CJ, Wood JL. J Am Chem Soc. 2006;128:1448–1449.For the synthesis of welwitindolinone D (3), see ref . (d) While the present manuscript was under review for publication, a report appeared in J. Am. Chem. Soc., ASAP on the total synthesis of welwitindolinone C (2): Huters AD, Quasdorf KW, Styduhar ED, Garg NK. J Am Chem Soc. 2011 doi: 10.1021/ja206538k.

    1. For a review on the Vilsmeier–Haack reaction, see: Meth-Con O, Stanforth SP. Comp Org Syn. 1991;2:777–794.For an example of deconjugative methylation of a cyclic enal, see: Burnell RH, Côté C, Théberge N. J Nat Prod. 1993;56:1459–1467.

LinkOut - more resources