Catalyst-Free Synthesis of Chromane-Type N,O-Acetals via Intramolecular Addition of Phenols to Enamines

Abstract

A new strategy to 2-aminochromanes through catalyst-free cascade reaction of 3-trifluoroacetyl-4H-chromenes and 4H-chromene-3-carbaldehydes with cyclic secondary amines is presented. The reaction proceeds through subsequent 1,4- and 1,2-additions of amine, bimolecular elimination of trifluoroacetamide or formamide, and 6-exo-trig cyclization. The latter stage is a very rare example of addition of phenols to enamines. The obtained semicyclic N,O-acetals were applied as useful precursors for the synthesis of other chromanes.

Key words

chromanes - 4H-chromenes - cascade reactions - enamines - cyclic secondary amines - N,O-acetals

• References

• 1 Yamazaki N, Kibayashi C. J. Syn. Org. Chem. Jpn. 2003; 61: 868

For reviews on N,O-acetals, see:
• 2a Warriner SL. In Science of Synthesis, Vol. 29. Bellus D. Thieme; Stuttgart: 2007: 7
• 2b Kim H, Rhee YH. Synlett 2012; 23: 2875
• 2c Huang Y.-Y, Cai C, Yang X, Lv Z.-C, Schneider U. ACS Catal. 2016; 6: 5747

For selected examples of reactions of N,O-acetals with carbonic nucleophiles, see:
• 3a Yu C, Huang H, Li X, Zhang Y, Li H, Wang W. Chem. Eur. J. 2016; 22: 9240
• 3b Sugiura M, Hagio H, Kobayashi S. Helv. Chim. Acta 2002; 85: 3678
• 3c Hamon M, Dickinson N, Devineau A, Bolien D, Tranchant M.-J, Taillier C, Jabin I, Harrowven DC, Whitby RJ, Ganesan A, Dalla V. J. Org. Chem. 2014; 79: 1900
• 3d Sugiura M, Hagio H, Hirabayashi R, Kobayashi S. J. Am. Chem. Soc. 2001; 123: 12510
• 3e Matsumura Y, Ikeda T, Onomura O. Heterocycles 2006; 66: 113
• 3f Wang X.-M, Liu Y.-W, Ma R.-J, Si C.-M, Wei B.-G. J. Org. Chem. 2019; 84: 11261
• 3g Onomura O, Ikeda T, Kuriyama M, Matsumura Y, Kamogawa S. Heterocycles 2010; 82: 325
• 4a Bruno O, Brullo C, Ranise A, Schenone S, Bondavalli F, Barocelli E, Ballabeni V, Chiavarini M, Tognolini M, Impicciatore M. Bioorg. Med. Chem. Lett. 2001; 11: 1397
• 4b Bruno O, Schenone S, Ranise A, Bondavalli F, Barocelli E, Ballabeni V, Chiavarini M, Bertoni S, Tognolini M, Impicciatore M. Bioorg. Med. Chem. Lett. 2001; 9: 629
• 5a Jurd L. J. Heterocycl. Chem. 1996; 33: 1919
• 5b Jiang N, Wang X, Yang Y, Dai W. Mini Rev. Med. Chem. 2006; 6: 885
• 6 Li Q.-Y, Zhang M, Hallis TM, DeRosier TA, Yue J.-M, Ye Y, Mais DE, Wang M.-W. Biochem. Biophys. Res. Commun. 2010; 391: 1531
• 7 Sasaki M, Tsuda M, Sekiguchi M, Mikami Y, Kobayashi J. Org. Lett. 2005; 7: 4261
• 8 Page PC. B, Heaney H, Rassias GA, Reignier S, Sampler EP, Talib S. Synlett 2000; 104
• 9a Botteghi C, Corrias T, Marchetti M, Paganelli S, Piccolo O. Org. Process Res. Dev. 2002; 6: 379
• 9b Ahman JB, Dillon BR, Pettman AJ. (Pfizer Ltd.) WO138440, 2007
• 9c Ciambecchini U, Turchetta S, de Ferra L, Zenoni M. (Chemi SPA) WO154854, 2011
• 10 Huang P, Cameron T, Jha A. Tetrahedron Lett. 2009; 50: 51
• 11a Jurd L. J. Heterocycl. Chem. 1997; 34: 601
• 11b Jurd L. J. Heterocycl. Chem. 1988; 25: 89
• 11c Benameur L, Bouaziz Z, Nebois P, Bartoll M.-H, Boitard M, Fillion H. Chem. Pharm. Bull. 1996; 44: 605
• 11d von Strandtmann M, Cohen MP, Shavel JJr. Tetrahedron Lett. 1965; 3103
• 11e von Strandtmann M, Cohen MP, Shavel JJr. J. Heterocycl. Chem. 1970; 7: 1311
• 11f Mahajan JR, Araujo HC. Synthesis 1976; 111
• 11g Katritzky AR, Lan X. Synthesis 1992; 761
• 11h Lukashenko AV, Osipov DV, Osyanin VA, Klimochkin YuN. Chem. Heterocycl. Compd. 2020; 56: 529
• 12 Klutchko S, Sonntag AC, von Strandtmann M, Shavel JJr. J. Org. Chem. 1973; 38: 3049
• 13 Paquette LA. Tetrahedron Lett. 1965; 1291
• 14a Jurd L. J. Heterocycl. Chem. 1991; 28: 983
• 14b Cimarelli C, Fratoni D, Palmieri G. Tetrahedron: Asymmetry 2011; 22: 1542
• 15 Osipov DV, Osyanin VA, Klimochkin YuN. Russ. Chem. Rev. 2017; 86: 625
• 16a Katritzky AR, Long Q.-H, Lue P, Jozwiak A. Tetrahedron 1990; 46: 8153
• 16b Blumenkopf N, Hecht OF. (General Aniline & Film Corporation) US Patent 3179661, 1965
• 17a Lukashenko AV, Osyanin VA, Osipov DV, Klimochkin YuN. J. Org. Chem. 2017; 82: 1517
• 17b Lukashenko AV, Osipov DV, Osyanin VA, Klimochkin YuN. Russ. J. Org. Chem. 2016; 52: 1817
• 18 For comprehensive review on chemistry of 5-formyl- and 5-trifluoroacetyl-3,4-dihydro-2H-pyrans and related 4Н-chromenes, see: Osipov DV, Osyanin VA, Klimochkin YuN. Targets Heterocycl. Syst. 2018; 22: 436
• 19 More recently, a similar selectivity to secondary cyclic amines has been found for 3-formylchromones, see: Korzhenko KS, Osipov DV, Osyanin VA, Klimochkin YuN. SynOpen 2019; 3: 164
• 20a Troxler F. Helv. Chim. Acta 1973; 56: 374
• 20b Slater NH, Brown NJ, Elsegood MR. J, Kimber MC. Org. Lett. 2014; 16: 4606
• 20c Markova MV, Mikhaleva AI, Sigalov MV, Morozova LV, Aliev IA, Trofimov BA. Chem. Heterocycl. Compd. 1989; 25: 501
• 20d Paz BM, Klier L, Næsborg L, Lauridse VH, Jensen F, Jørgensen KA. Chem. Eur. J. 2016; 22: 16810
• 21a Arduini A, Bosi A, Pochini A, Ungaro R. Tetrahedron 1985; 41: 3095
• 21b Cravotto G, Nano GM, Palmisano G, Pilati T, Tagliapietra S. J. Heterocycl. Chem. 2001; 38: 965
• 21c Palasz A. Synthesis 2010; 4021
• 21d Cimarelli C, Fratoni D, Palmieri G. Tetrahedron: Asymmetry 2011; 22: 1542
• 21e Li K, Tunge JA. J. Org. Chem. 2005; 70: 2881
• 22 For the first example, see: Osipov DV, Melnikova IV, Osyanin VA, Lukashenko AV, Klimochkin YuN. J. Fluorine Chem. 2017; 202: 71

For review on synthesis and chemistry of 2-chromanols, see:
• 23a Mattalia J.-MR, Attolini MM. ARKIVOC 2013; (i): 101

For a very recent study on 2-chromanols from our group, see:
• 23b Semenova IA, Korzhenko KS, Osipov DV, Osyanin VA, Klimochkin YuN. Chem. Heterocycl. Compd. 2020; 56: 311
• 24 For a very recent and important example of enantioselective synthesis of related 2-arylchromanes, see: Sakamoto K, Nishimura T. Adv. Synth. Catal. 2019; 361: 2124
• 25 Lukashenko AV, Osyanin VA, Osipov DV, Klimochkin YuN. Chem. Heterocycl. Compd. 2016; 52: 711
• 26 CCDC 1838635 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.