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. 2013 Feb 20;54(8):913-917.
doi: 10.1016/j.tetlet.2012.11.125.

Total Synthesis of (±)-Cis-Trikentrin B via Intermolecular 6,7-Indole Aryne Cycloaddition and Stille Cross-Coupling

Nalin Chandrasoma  1 , Neil Brown  2 , Allen Brassfield  1 , Alok Nerurkar  1 , Susana Suarez  1 , Keith R Buszek  2
Affiliations

Total Synthesis of (±)-Cis-Trikentrin B via Intermolecular 6,7-Indole Aryne Cycloaddition and Stille Cross-Coupling

Nalin Chandrasoma et al. Tetrahedron Lett. .

Abstract

An efficient total synthesis of the annulated indole natural product (±)-cis-trikentrin B was accomplished by means of a regioselectively generated 6,7-indole aryne cycloaddition via selective metal-halogen exchange from a 5,6,7-tribromoindole. The unaffected C-5 bromine was subsequently used for a Stille cross-coupling to install the butenyl side chain and complete the synthesis. This strategy provides rapid access into the trikentrins and the related herbindoles, and represents another application of this methodology to natural products total synthesis. The required 5,6,7-indole aryne precursor was prepared using the Leimgruber-Batcho indole synthesis.

Keywords: Indole; Stille; aryne; benzofuran; cross-coupling; cycloaddition; herbindole; natural products; total synthesis; trikentrin.

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Figures

Figure 1
Figure 1
The trikentrin and herbindole natural products.
Scheme 1
Scheme 1
Indole arynes via metal-halogen exchange and their cycloadditions with furan.
Scheme 2
Scheme 2
First-generation (±)-cis-trikentrin A synthesis.
Scheme 3
Scheme 3
Second-generation (±)-cis-trikentrin A synthesis.
Scheme 4
Scheme 4
Retrosynthetic analysis of cis-trikentrin B.
Scheme 5
Scheme 5
Synthesis of 5,6,7-tribromoindole via Bartoli route.
Scheme 6
Scheme 6
Synthesis of 5,6,7-tribromoindole via Leimgruber-Batcho route.
Scheme 7
Scheme 7
Regioselective C-7 metal-halogen exchange.
Scheme 8
Scheme 8
Raney nickel reduction of 35
Scheme 9
Scheme 9
Fujimoto reduction of 34
Scheme 10
Scheme 10
Final step: Stille cross-coupling
See this image and copyright information in PMC

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