Sequential [3,3]-Sigmatropic Rearrangement/Nucleophilic Aryl­ation of N-(Benzoyloxy)enamides towards the Preparation of Cyclic β-Aryl-β-amino Alcohols

Abstract

A new method has been developed for the efficient synthesis of cyclic β-aryl-β-amino alcohol derivatives bearing a tetrasubstituted carbon center via the [3,3]-sigmatropic rearrangement of N-(benzoyl­oxy)enamides followed by nucleophilic arylation reaction with a range of triarylaluminum reagents. The resulting products were converted into the corresponding sterically congested cyclic β-amino alcohols, as well as the dissociative anesthetic agent Tiletamine.

Key words

β-amino alcohols - enamides - sigmatropic rearrangement - imines - nucleophilic addition - organoaluminum reagents

• References


For selected examples, see:
• 1a Ghosh AK. J. Org. Chem. 2010; 75: 7967
• 1b Endo A, Yanagisawa A, Abe M, Tohma S, Kan T, Fukuyama T. J. Am. Chem. Soc. 2002; 124: 6552
• 1c Nicolaou KC, Zou B, Dethe DH, Li DB, Chen DY.-K. Angew. Chem. Int. Ed. 2006; 45: 7786
• 1d Liu Q, Ferreira EM, Stoltz BM. J. Org. Chem. 2007; 72: 7352
• 2 Aubard GG, Calvet AP, Grouhel A, Jacobelli H, Junien J.-L, Pascaud XB. L, Roman FJ. A. EP 384088, 1990 ; Chem. Abstr. 1991, 114, 184974.
• 3a Delgado O, Monteagudo A, Van Gool M, Trabanco AA, Fustero S. Org. Biomol. Chem. 2012; 10: 6758
• 3b Huestis MP, Liu W, Volgraf M, Purkey HE, Yu C, Wang W, Smith D, Vigers G, Dutcher D, Hunt KW, Siu M. Tetrahedron Lett. 2013; 54: 5802
• 4 Tang TP, Volkman SK, Ellman JA. J. Org. Chem. 2001; 66: 8772
• 5 Chen Y.-J, Chen Y.-H, Feng C.-G, Lin G.-Q. Org. Lett. 2014; 16: 3400

For other examples utilizing nucleophilic addition to N-sulfinylimines, see:
• 6a García Ruano JL, Alemán J, Parra A. J. Am. Chem. Soc. 2005; 127: 13048
• 6b Chemla F, Ferreira F, Gaucher X, Palais L. Synthesis 2007; 1235
• 6c Jiang J.-L, Yao M, Lu C.-D. Org. Lett. 2014; 16: 318
• 7a Steinig AG, Spero DM. J. Org. Chem. 1999; 64: 2406
• 7b Simon J, Chelain E, Brigaud T. Org. Lett. 2012; 14: 604

For selected examples of preparation of β-amino alcohol derivatives from enamines, see:
• 8a Goralski CT, Singaram B. ARKIVOC 2012; (vii): 88
• 8b García Martníez A, TesoVilar E, García Fraile A, de la Moya Cerero S, Martínez Ruiz P, Subramanian LR. Tetrahedron: Asymmetry 1996; 7: 1257
• 8c Pennemann H, Wallbaum S, Martens J. Tetrahedron: Asymmetry 2000; 11: 2133

For selected examples of β-oxygenation of enamides, see:
• 9a Lu M, Lu Y, Zhu D, Zeng X, Li X, Zhong G. Angew. Chem. Int. Ed. 2010; 49: 8588
• 9b Bekkaye M, Su Y, Masson G. Eur. J. Org. Chem. 2013; 3978
• 9c Drouet F, Zhu J, Masson G. Adv. Synth. Catal. 2013; 355: 3563
• 10 Tabolin AA, Ioffe SL. Chem. Rev. 2014; 114: 5426
• 11a House HO, Forrest AR. J. Org. Chem. 1969; 34: 1340
• 11b Cummins CH, Coates RM. J. Org. Chem. 1983; 48: 2070
• 11c Vosburg DA, Weiler S, Sorensen E. Chirality 2003; 15: 156
• 11d Beshara CS, Hall A, Jenkins RL, Jones KL, Jones TC, Killeen NM, Taylor PH, Thomas SP, Tomkinson NC. O. Org. Lett. 2005; 7: 5729
• 11e Smithen DA, Mathews CJ, Tomkinson NC. O. Org. Biomol. Chem. 2012; 10: 3756
• 12a Bhatt MV, Rao CG, Rengaraju S. J. Chem. Soc., Chem. Commun. 1976; 103
• 12b Reddy GS, Bhatt MV. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1980; 19: 213
• 12c Figueira VB. C, Esqué AG, Varala R, González-Bello C, Prabhakar S, Lobo AM. Tetrahedron Lett. 2010; 51: 2029
• 13a Miyoshi M, Matsuya S, Tsugawa M, Sato S, Ueda M, Miyata O. Org. Lett. 2013; 15: 3374
• 13b Sato S, Takeda N, Miyoshi T, Ueda M, Miyata O. Eur. J. Org. Chem. 2015; 3899
• 14 When PhAlMe₂ was used in the sequential rearrangement/phenylation reaction, no methylated product, which would be produced by the addition of a methyl group to the N-(trifluoroacetyl)ketimine, was obtained. In the case of PhAlEt₂, a small amount of the ethylated product was detected.
• 15 When Et₃Al was used in the sequential [3,3]-sigmatropic rearrangement/nucleophilic ethylation reaction of 1a, ethylated product was obtained in 10% yield.
• 16 Ketamine is included as a general anesthetic agent in the 14th WHO model list of essential medicines, see the discussion in: WHO Expert Committee on Drug Dependence (ECDD) 34th Report. WHO Technical Report Series 942; Geneva: Switzerland: 2006

For selected examples of reports describing the synthesis of ketamine, see:
• 17a Stevens CL. US 3254124, 1968 ; Chem. Abstr. 1968, 65, 5414.
• 17b Yokoyama R, Matsumoto S, Nomura S, Higaki T, Yokoyama T, Kiyooka S. Tetrahedron 2009; 65: 5181
• 17c Yokoyama T, Yokoyama R, Nomura S, Matsumoto S, Fujiyama R, Kiyooka S. Bull. Chem. Soc. Jpn. 2009; 82: 1528
• 18a d’Ischia M, Napolitano A, Pezzella A In Comprehensive Heterocyclic Chemistry III . Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Elsevier; Oxford: 2008: 353
• 18b Keay BA, Hopkins JM, Dibble PW In Comprehensive Heterocyclic Chemistry III . Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Elsevier; Oxford: 2008: 571
• 18c Schatz J, Brendgen T, Schühle D In Comprehensive Heterocyclic Chemistry III . Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Elsevier; Oxford: 2008: 931

For recent examples of reports describing the synthesis of Duloxetine hydrochloride, see:
• 19a Träff A, Lihammar R, Bäckvall J.-E. J. Org. Chem. 2011; 76: 3917
• 19b Suzuki Y, Iwata M, Yazaki R, Kumagai N, Shibasaki M. J. Org. Chem. 2012; 77: 4496
• 19c Calow AD. J, Fernández E, Whiting A. Org. Biomol. Chem. 2014; 12: 6121
• 20 For the synthesis of Tiotropium, see: Banholzer R, Bauer R, Reichl R. EP 418716, 1991 ; Chem. Abstr. 1992, 116. 20937.

For recent examples of reports describing the synthesis of Clopidogrel, see:
• 21a Wang L, Shen J, Tang Y, Chen Y, Wang W, Cai Z, Du Z. Org. Process Res. Dev. 2007; 11: 487
• 21b van der Meijden MW, Leeman M, Gelens E, Noorduin WL, Meekes H, van Enckevort WJ. P, Kaptein B, Vlieg E, Kellogg RM. Org. Process Res. Dev. 2009; 13: 1195
• 21c Sadhukhan A, Saravanan S, Khan NH, Kureshy RI, Abdi SH. R, Bajaj HC. J. Org. Chem. 2012; 77: 7076
• 22 For the synthesis of Prasugrel hydrochloride, see: Aalla S, Gilla G, Metil DS, Anumula RR, Vummenthala PR, Padi PR. Org. Process Res. Dev. 2012; 16: 240
• 23 For the synthesis of Rivaroxaban, see: Roehrig S, Straub A, Pohlmann J, Lampe T, Pernerstorfer J, Schlemmer K.-H, Reinemer P, Perzborn E. J. Med. Chem. 2005; 48: 5900
• 24 For the synthesis of Tiletamine hydrochloride, see: Lapin YA, Sanchez IH. US 6147226, 2000 ; Chem. Abstr. 2000, 133, 350130.
• 25 The treatment of Tiletamine with HCl in Et₂O (1.0 M) afforded Tiletamine hydrochloride in quantitative yield.
• 26 Zhukovskaya NA, Dikusar EA. Russ. J. Org. Chem. 2010; 46: 180

Triarylaluminum and Triheteroarylaluminum were prepared the same as in our previous work, see:
• 27a Miyoshi T, Miyakawa T, Ueda M, Miyata O. Angew. Chem. Int. Ed. 2011; 50: 928
• 27b Miyoshi T, Sato S, Tanaka H, Hasegawa C, Ueda M, Miyata O. Tetrahedron Lett. 2012; 53: 4188
• 27c Miyoshi T, Takeda N, Fukami M, Sato S, Ueda M, Miyata O. Chem. Pharm. Bull. 2014; 62: 927
• 28 Parcell RF, Sanchez JP. J. Org. Chem. 1981; 46: 5229
• 29 Hassner A, Lorber ME, Heathcock CH. J. Org. Chem. 1967; 32: 540
• 30 Merino E, Melo RP. A, Ortega-Guerra M, Ribagorda M, Carreño MC. J. Org. Chem. 2009; 74: 2824