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
. 2010 Nov 5;12(21):4739-41.
doi: 10.1021/ol102233g.

Diastereo- and enantioselective copper-catalyzed intramolecular carboamination of alkenes for the synthesis of hexahydro-1H-benz[f]indoles

Lei Miao  1 , Imranul Haque, Maria R Manzoni, Weng Siong Tham, Sherry R Chemler
Affiliations

Diastereo- and enantioselective copper-catalyzed intramolecular carboamination of alkenes for the synthesis of hexahydro-1H-benz[f]indoles

Lei Miao et al. Org Lett. .

Abstract

A new method for the enantioselective synthesis of hexahydro-1H-benz[f]indoles is described. This copper-catalyzed enantioselective intramolecular alkene carboamination process can install vicinal tertiary and quaternary carbon stereocenters with high levels of diastereo- and enantioselectivity. The C-C bond-forming component of the reaction constitutes a C-H functionalization and no electronic activation of the aryl ring that undergoes addition is required. A known 5-HT(1A) receptor antagonist was synthesized efficiently using this method.

PubMed Disclaimer

Figures

Figure 1
Figure 1
aEnantioselective Carboamination Scope. a20 mol % Cu(OTf)2 and 25 mol % (R,R)-Ph-Box were combined in PhCF3 (0.1 M w/r to 1) and heated at 60 °C for 2 h in a pressure tube, then 1, K2CO3 (100 mol %), MnO2 (300 mol %) were added and the reaction was heated at 120 °C for 24 h. Yield refers to product isolated from flash chromatography on SiO2. Enantioselectivity (%ee) was determined by chiral HPLC. bReaction run at 110 °C. cYield is for combined regioisomeric mixture, dr and %ee were the same for both isomers. SES = trimethylsilylethlysulfonyl, Bs = benzenesulfonyl, PMBS = 4-methoxybenzenesulfonyl, PCBS = 4-chlorobenzenesulfonyl, Ns = 4-nitrobenzenesulfonyl.
Scheme 1
Scheme 1
Benz[f]indole via Carboamination Sequence
Scheme 2
Scheme 2
Addition and Rearrangement
Scheme 3
Scheme 3
Transition State Model for Enantioselectivity
Scheme 4
Scheme 4
Diastereoselective Carboaminations
See this image and copyright information in PMC

References

    1. Reviews: Wolfe JP. Eur J Org Chem. 2007:571.Wolfe JP. Synlett. 2008:2913.Chemler SR. Org & Biomol Chem. 2009;7:3009.

    1. Recent palladium-catalyzed carboaminations/carbonylations: Tsujihara T, Shinohara T, Takenaka K, Takizawa S, Onitsuka K, Hatanaka M, Sasai H. J Org Chem. 2009;74:9274.Mai DN, Wolfe JP. J Am Chem Soc. 2010;132:12157.He W, Yip KT, Zhu NY, Yang D. Org Lett. 2009;11:5626.Scarborough CC, Stahl SS. Org Lett. 2006;8:3251.Houlden CE, Bailey CD, Ford JG, Gagne MR, Lloyd-Jones GC, Booker-Milburn KI. J Am Chem Soc. 2008;130:10066.Scarborough CC, Bergant A, Sazama GT, Guzei IA, Spencer LC, Stahl SS. Tetrahedron. 2009;65:5084.Rosewall CF, Sibbald PA, Liskin DV, Michael FE. J Am Chem Soc. 2009;131:9488.A gold-catalyzed carboamination: Zhang G, Cui L, Wang Y, Zhang L. J Am Chem Soc. 2010;132:1474.

    1. Copper-catalyzed carboaminations: Zeng W, Chemler SR. J Am Chem Soc. 2007;129:12948.Sherman ES, Chemler SR. Adv Synth & Catal. 2009;351:467.Cu(II)-promoted carboaminations: Sherman ES, Fuller PH, Kasi D, Chemler SR. J Org Chem. 2007;72:3896.Fuller PH, Chemler SR. Org Lett. 2007;9:5477.

    1. Lin CH, Haadsma-Svensson SR, Phillips G, Lahti RA, McCall RB, Piercey MF, Schreur PJKD, Von Voigtlander PF, Smith MW, Chidester CG. J Med Chem. 1993;36:1069. - PubMed
    1. Park HJ, Lee HJ, Min HY, Chung HJ, Suh ME, Park-Choo HY, Kim C, Kim HJ, Seo EK, Lee SK. Eur J Pharm. 2005;527:31. and references therein. - PubMed

Publication types