Asymmetric Hydrogenation of Cyclic Imines and Enamines: Access to 1,5-Benzodiazepine Pharmacophores

Dedicated to Prof. Dieter Enders on the occasion of his 70^th birthday

Abstract

A new strategy towards the pharmacologically relevant class of dihydro-1,5-benzodiazepines was developed by applying a rhodium-catalyzed asymmetric hydrogenation. The approach represents an efficient protocol providing access to the optically active products in excellent yields (up to 99%) and with high enantioselectivities (up to 92% ee). The versatility of the methodology was demonstrated by a broad substrate scope including alkyl, aryl, and heteroaryl substituents as well as halides. Furthermore, investigations regarding the reaction mechanism were performed and unraveled a preferred reaction of the tautomeric enamine in the rhodium-catalyzed asymmetric hydrogenation.

Key words

asymmetric hydrogenation - rhodium catalysis - benzodiazepines - reduction - enamine

• References

• 1 Chemistry of Heterocyclic Compounds: A Series of Monographs. Chemistry of Heterocyclic Compounds: Bicyclic Diazepines: Diazepines with an Additional Ring. Vol. 50. Fryer RI. Wiley; New York/Chichester: 1991
• 2 Xie J.-H, Zhu S.-F, Zhou Q.-L. Chem. Rev. 2011; 111: 1713
• 3 Horton DA, Boume GT, Smythe ML. Chem. Rev. 2003; 103: 893
• 4 Evans BE, Rittle KE, Bock MG, DiPardo RM, Freidinger RM, Whitter WL, Lundell GF, Veber DF, Anderson PS, Chang RS. L, Lotti VJ, Cerino DJ, Chen TB, Kling PJ, Kunkel KA, Springer JP, Hirshfeld J. J. Med. Chem. 1988; 31: 2235
• 5 Sternbach LH. Angew. Chem., Int. Ed. Engl. 1971; 10: 34
• 6 Lancel M, Steiger A. Angew. Chem. Int. Ed. 1999; 38: 2852
• 7 Sternbach LH. J. Med. Chem. 1979; 22: 1
• 8 Olkkola KT, Ahonen J In Modern Anesthetics, Handbook of Experimental Pharmacology. Vol. 182. Schüttler J, Schwilden H. Springer; Berlin: 2008: 335
• 9a Nadendla RR. Principles of Organic Medicinal Chemistry. New Age International Ltd; New Delhi: 2005: 83-88
• 9b Nadendla RR. Principles of Organic Medicinal Chemistry. New Age International Ltd; New Delhi: 2005: 111-114
• 10 Integrated Pharmacology. 1st ed. Page CP, Curtis M, Sutter M, Walker M, Hoffman B. CV Mosby; London: 1997
• 11 Landquist JK In Comprehensive Heterocyclic Chemistry. Vol. 1. Katritzky AR, Rees CW. Elsevier; Oxford: 1997: 166-170
• 12 James GL, Goldstein JL, Brown MS, Rawson TE, Somers TC, McDowell RS, Crowley CW, Lucas BK, Levinson AD, Marsters JC. Jr. Science 1993; 260: 1937
• 13 Liskamp RM. J. Angew. Chem., Int. Ed. Engl. 1994; 33: 305
• 14 Hsu M.-C, Schutt AD, Holly M, Slice LW, Sherman MI, Richman DD, Potash MJ, Volsky DJ. Science 1991; 254: 1799
• 15 Breslin HJ, Kukla MJ, Ludovici DW, Mohrbacher R, Ho W, Miranda M, Rodgers JD, Hitchens TK, Leo G, Gauthier DA, Ho CY, Sctot MK, De Clercq E, Pauwels R, Andries K, Janssen MA. C, Janssen PA. J. Med. Chem. 1995; 38: 771
• 16 Bub O. German Patent DE 1913536, 1970
• 17 Bauer A, Weber KH, Unruh M. Arch. Pharm. (Weinheim) 1972; 305: 557
• 18 Bauer A, Merz H, Zeile K, Danneberge P, Weber KH, Giesemann R. German Patent DE 1929656, 1970
• 19 Mueller E. Pharmacopsychiatry 1985; 18: 10
• 20 Mueller E, Groh B, Bub O, Hofmann HP, Kreiskott K. Pharmacopsychiatry 1986; 19: 314
• 21 Bub O, Friedrich L, Hofmann HP, Kreiskott H, Zimmermann F. German Patent DE 2052840, 1972
• 22 Lee J, Gauthier D, Rivero RA. J. Org. Chem. 1999; 64: 3060
• 23 Herpin TF, Van Kirk KG, Salino JM, Yu ST, Labaudiniere RF. J. Comb. Chem. 2000; 2: 513
• 24 Nawrocka W, Sztuba B, Zimecki M. Arch. Pharm. (Weinheim) 2001; 334: 11
• 25 Zhao H.-Y, Liu G. J. Comb. Chem. 2007; 9: 1164
• 26 Rida M, El Meslouhi H, Ahabchane NH, Garrigues B, Es-Safi N, Essassi EM. Open Org. Chem. J. 2008; 2: 83
• 27 Hoyt SB, London C, Wyvratt MJ, Fisher MH, Cashen DE, Felix JP, Garcia ML, Li X, Lyons KA, MacIntyre DE, Martin WJ, Priest BT, Smith MM, Warren VA, Williams BS, Kaczorowski GJ, Parsons WH. Bioorg. Med. Chem. Lett. 2008; 18: 1963
• 28a Rueping M, Merino E, Koenigs RM. Adv. Synth. Catal. 2010; 352: 2629
• 28b Rueping M, Dufour J, Schoepke FR. Green Chem. 2011; 13: 1084
• 28c Rueping M, Sugiono E, Schoepke FR. Synlett 2010; 852

Further examples:
• 28d Azap C, Sugiono E, Theissmann T. Synlett 2005; 2367
• 28e Rueping M, Sugiono E, Azap C, Theissmann T, Bolte M. Org. Lett. 2005; 7: 3781
• 28f Rueping M, Theissmann T, Antonchick AP. Synlett 2006; 1071
• 28g Rueping M, Antonchick AP, Theissmann T. Angew. Chem. Int. Ed. 2006; 45: 6751
• 28h Rueping M, Antonchick AP, Theissmann T. Angew. Chem. Int. Ed. 2006; 45: 3683
• 28i Rueping M, Antonchick AP. Angew. Chem. Int. Ed. 2007; 46: 4562
• 28j Rueping M, Antonchick AP. Angew. Chem. Int. Ed. 2008; 47: 5836
• 28k Rueping M, Theissmann T, Raja S, Bats JB. Adv. Synth. Catal. 2008; 350: 1001
• 28l Rueping M, Brinkmann C, Antonchick AP, Atodiresei I. Org. Lett. 2010; 12: 4604
• 28m Rueping M, Nachtsheim BJ. Synlett 2010; 119
• 28n Rueping M, Stoeckel M, Sugiono E, Theissmann T. Tetrahedron 2010; 66: 6565
• 28o Rueping M, Theissmann T. Chem. Sci. 2010; 1: 473
• 28p Rueping M, Sugiono E, Steck A, Theissmann T. Adv. Synth. Catal. 2010; 352: 281
• 28q Rueping M, Tato F, Schoepke FR. Chem. Eur. J. 2010; 16: 2688
• 28r Rueping M, Hubener L. Synlett 2011; 1243
• 28s Rueping M, Theissmann T, Stoeckel M, Antonchick AP. Org. Biomol. Chem. 2011; 9: 6844
• 28t Rueping M, Bootwicha T, Sugiono E. Beilstein J. Org. Chem. 2012; 8: 300
• 28u Sugiono E, Rueping M. Beilstein J. Org. Chem. 2013; 9: 2457
• 28v Liao H.-H, Hsiao C.-C, Sugiono E, Rueping M. Chem. Commun. 2013; 49: 7953
• 28w Hsiao C.-C, Liao H.-H, Sugiono E, Atodiresei I, Rueping M. Chem. Eur. J. 2013; 19: 9775
• 28x Kadyrov R, Koenigs RM, Brinkmann C, Voigtlaender D, Rueping M. Angew. Chem. Int. Ed. 2009; 48: 7556
• 29 Chen X, Zheng Y, Shu C, Yuan W, Liu B, Zhang X. J. Org. Chem. 2011; 76: 9109
• 30 For an asymmetric hydrogenation of 1,5-benzothiazepines, see: Li W, Schlepphorst C, Daniliuc C, Glorius F. Angew. Chem. Int. Ed. 2016; 55: 3300
• 31 The Handbook of Homogeneous Hydrogenation. Vol. 1. de Vries JG, Elsevier CJ. Wiley-VCH; Weinheim: 2007

For selected books and book chapters, see:
• 32a Stereoselective Formation of Amines. Li W, Zhang X. Springer; Berlin: 2014
• 32b Blaser H.-U, Spindler F. Catalytic Asymmetric Hydrogenation of C=N Functions. In Organic Reactions. Wiley; New York: 2009
• 32c Spindler F, Blaser H.-U. Enantioselective Hydrogenation of C=N Functions and Enamines. In The Handbook of Homogeneous Hydrogenation. Vol. 1. de Vries JG, Elsevier CJ. Wiley-VCH; Weinheim: 2007: 1193-1214
• 32d Blaser H.-U, Spindler F. Hydrogenation of Imino Groups. In Comprehensive Catalysis. Jacobsen EN, Pfaltz A, Yamamoto H. Springer; Berlin: 2000: 246-264

For selected reviews, see:
• 33a Ref. 2.
• 33b Wang D.-S, Chen Q.-A, Lu S.-M, Zhou Y.-G. Chem. Rev. 2012; 112: 2557
• 33c Zhou Y.-G. Acc. Chem. Res. 2007; 40: 1357
• 33d Chen Q.-A, Ye Z.-S, Duan Y, Zhou Y.-G. Chem. Soc. Rev. 2013; 42: 497
• 33e Fleury-Brégeot N, de la Fuente V, Castillón S, Claver C. ChemCatChem 2010; 2: 1346
• 33f Hopmann KH, Bayer A. Coord. Chem. Rev. 2014; 268: 59
• 33g Yu Z, Jin W, Jiang Q. Angew. Chem. Int. Ed. 2012; 51: 6060
• 33h Balakrishna B, Nunez-Rico JL, Vidal-Ferran A. Eur. J. Org. Chem. 2015; 5293
• 34 Blaser H.-U, Pugin B, Spindler F. Asymmetric Hydrogenation. In Organometallics as Catalysts in the Fine Chemical Industry. Beller M, Blaser H.-U. Springer; Berlin: 2012: 65-102
• 35 Blaser H.-U. Industrial Asymmetric Hydrogenation. In Applications of Transition Metal Catalysis in Drug Discovery and Development: An Industrial Perspective. Crawley ML, Trost BM. Wiley; Hoboken: 2012: 315-342
• 36 Krossing I, Raabe I. Angew. Chem. Int. Ed. 2004; 43: 2066
• 37 Nishida H, Takada N, Yoshimura M. Bull. Chem. Soc. Jpn. 1984; 57: 2600
• 38 Golden JH, Mutolo PF, Lobkovsky EB, DiSalvo FJ. Inorg. Chem. 1994; 33: 5374
• 39 Iridium Complexes in Organic Synthesis. Oro LA, Claver C. Wiley-VCH; Weinheim: 2009: 1-140
• 40 Fabrello A, Bachelier A, Urrutigoity M, Kalck P. Coord. Chem. Rev. 2010; 254: 273