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. 2008 Aug 21;10(16):3485-8.
doi: 10.1021/ol801264u. Epub 2008 Jul 19.

A versatile cyclodehydration reaction for the synthesis of isoquinoline and beta-carboline derivatives

Mohammad Movassaghi  1 , Matthew D Hill
Affiliations

A versatile cyclodehydration reaction for the synthesis of isoquinoline and beta-carboline derivatives

Mohammad Movassaghi et al. Org Lett. .

Abstract

The direct conversion of various amides to isoquinoline and beta-carboline derivatives via mild electrophilic amide activation, with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine, is described. Low-temperature amide activation followed by cyclodehydration upon warming provides the desired products with short overall reaction times. The successful use of nonactivated and halogenated phenethylene derived amides, N-vinyl amides, and optically active substrates is noteworthy.

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Figures

Figure 1
Figure 1
Synthesis of isoquinoline and β-carboline derivatives.a
Scheme 1
Scheme 1
Intramolecular dehydrative cyclization.
Figure 2
Figure 2
Tf2O–2-ClPyr promoted oxidation of 3,4-dihydro-β-carbolines and 3,4-dihydroisoquinolines.a
See this image and copyright information in PMC

References

    1. Bischler A, Napieralski B. Ber. 1893;26:1903.
    2. Whaley WM, Govindachari TR. Org. React. 1951;6:74.

    1. For representative reports, see: Tóth J, Nedves A, Dancsó A, Blaskó G, Töke L, Nyerges M. Synthesis. 2007:1003.Spaggiari A, Davoli P, Blaszczak LC, Prati F. Synlett. 2005:661.Banwell MG, Bissett BD, Busato S, Cowden CJ, Hockless DCR, Holman JW, Read RW, Wu AW. J. Chem. Soc., Chem. Commun. 1995:2551.Larsen RD, Reamer RA, Corley EG, Davis P, Grabowski EJJ, Reider PJ, Shinkai I. J. Org. Chem. 1991;56:6034.Hendrickson JB, Schwartzman SM. Tetrahedron Lett. 1975;16:277.

    1. For reviews on isoquinolines and their reduced derivatives, see Jones G. In: Comprehensive Heterocyclic Chemistry II. Katritzky AR, Rees CW, Scriven EFV, McKillop A, editors. Vol. 5. Pergamon; Oxford: 1996. p. 167.Bentley KW. Nat. Prod. Rep. 2006;23:444.Kartsev VG. Med. Chem. Res. 2004;13:325.Chrzanowska M, Rozwadowska MD. Chem. Rev. 2004;104:3341.Joule JA, Mills K. Heterocyclic Chemistry. 4th ed. Blackwell Science Ltd.; Cambridge MA: 2000. p. 121.Rozwadowska MD. Heterocycles. 1994;39:903. For a review on β-carbolines and their reduced derivatives, see Love BE. Org. Prep. Proced. Int. 1996;28:3.

    1. Movassaghi M, Hill MD. J. Am. Chem. Soc. 2006;128:14254. - PubMed
    2. Movassaghi M, Hill MD, Ahmad OK. J. Am. Chem. Soc. 2007;129:10096. - PubMed

    1. For recent advances in synthesis of N-vinyl and N-aryl amides, see: Muci AR, Buchwald SL. Top. Curr. Chem. 2002;219:131.Hartwig JF. In: Handbook of Organopalladium Chemistry for Organic Synthesis. Negishi E, editor. Wiley-Interscience; New York: 2002. p. 1051.Beletskaya IP, Cheprakov AV. Coordin. Chem. Rev. 2004;248:2337.Dehli JR, Legros J, Bolm C. Chem. Commun. 2005:973.

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