Electrophilic ipso-Halocyclization of N-Phenyl-N-triflylpropiolamides Leading to 8-Halo-1-azaspiro[4.5]deca-3,6,9-trien-2-ones

Abstract

N-Phenyl-N-triflylpropiolamides react with iodine chloride or iodine bromide by an intramolecular electrophilic ipso-halocyclization/nucleophilic halide addition sequence to furnish cyclohexadiene-spiro-γ-lactams. These products can undergo cleavage of the amide bond with primary amines and of the N–C_spiro bond with secondary amines, leading to N-alkyl-2-iodo-3-phenylacrylamides and N-(4-halophenyl)-2-iodo-3-(2-triflylamino)phenylacrylamides, respectively.

Key words

electrophilic addition - propiolamides - γ-lactams - spiro compounds - triflylamides

• References


Reviews:
• 1a Zheng Y.-J, Tice CM. Expert Opin. Drug Discov. 2016; 11: 831
• 1b Zheng Y, Tice CM, Singh SB. Bioorg. Med. Chem. Lett. 2014; 24: 3673
• 2 Review: Müller G, Berkenbosch T, Benningshof JC. J, Stumpfe D, Bajorath J. Chem. Eur. J. 2017; 23: 703
• 3 Review: Reddy CR, Prajapti SK, Warudikar K, Ranjan R, Rao BB. Org. Biomol. Chem. 2017; 15: 3130
• 4 Tutorial review: Wu W.-T, Zhang L, You S.-L. Chem. Soc. Rev. 2016; 45: 1570
• 5 Appel TR, Yehia NA. M, Baumeister U, Hartung H, Kluge R, Ströhl D, Fanghänel E. Eur. J. Org. Chem. 2003; 47
• 6 Zhang X, Larock RC. J. Am. Chem. Soc. 2005; 127: 12230
• 7a Tang B.-X, Tang D.-J, Tang S, Yu Q.-F, Zhang Y.-H, Liang Y, Zhong P, Li J.-H. Org. Lett. 2008; 10: 1063
• 7b Yu Q.-F, Zhang Y.-H, Yin Q, Tang B.-X, Tang R.-Y, Zhong P, Li J.-H. J. Org. Chem. 2008; 73: 3658
• 7c Tang B.-X, Yin Q, Tang R.-Y, Li J.-H. J. Org. Chem. 2008; 73: 9008
• 7d Wang Z.-Q, Tang B.-X, Zhang H.-P, Wang F, Li J.-H. Synthesis 2009; 891
• 7e Tang B.-X, Zhang Y.-H, Song R.-J, Tang D.-J, Deng G.-B, Wang Z.-Q, Xie Y.-X, Xia Y.-Z, Li J.-H. J. Org. Chem. 2012; 77: 2837
• 8 Zhang X, Sarkar S, Larock RC. J. Org. Chem. 2006; 71: 236
• 9 Review: Vessally E, Babazadeh M, Didehban K, Hosseinian A, Edjlali L. Curr. Org. Chem. 2018; 22: 286
• 10 Mini review: Liang X.-W, Zheng C, You S.-L. Chem. Eur. J. 2016; 22: 11918
• 11 Wang LJ, Zhu HT, Qiu YF, Liu XY, Liang YM. Org. Biomol. Chem. 2014; 12: 643
• 12 Fiore VA, Maas G. Tetrahedron 2019; 75: 3586
• 13a Fiore VA, Maas G. Z. Naturforsch., B 2019; 74: 671 ; https://doi.org/10.1515/znb-2019-0100
• 13b Fiore VA, Freisler C, Maas G. Beilstein J. Org. Chem. 2019; 15: 2603
• 13c Fiore VA. Doctoral Thesis . Ulm University; Germany: 2018
• 14 The position of the iodine atom at C-2 follows from an HSQC NMR experiment, which shows a cross-peak between the olefinic proton signal and the ¹³C signal at 113.48 ppm, but not to the signal at δ_C = 81.81. The chemical shift of the olefinic C-2 nucleus corresponds to the strong shielding effect of iodine.
• 15 For analogous I–Hal additions at acetylenic carbonyl compounds and structure assignments, see: Langle S, Ngi SI, Anselmi E, Abarbri M, Thibonnet J, Duchene A. Synthesis 2007; 1724
• 16 For NMR data and structures of (E)- and (Z)-3-iodo-2-bromoacrylic acids, see: Lugh A, McKague AB. Synth. Commun. 2006; 36: 3387
• 17 Rissanen K. CrystEngComm 2008; 10: 1107
• 18 In several 3-iodopropiolamides, we have found contact distances I···O in the range 2.754(2)–2.858(3) Å and I···O–C angles of 170.9(5)–175.6(4)°; see: Kratzer P, Ramming B, Römisch S, Maas G. CrystEngComm 2015; 17: 4486
• 19a Hendrickson JB, Bergeron R. Tetrahedron Lett. 1973; 46: 4607
• 19b Guillard S, Aramini A, Cesta MC, Colagioia S, Coniglio S, Genovese F, Nano G, Nuzzo E, Orlando V, Allegretti M. Tetrahedron 2006; 62: 5608
• 20 For transamidation reactions of N-acylmethanesulfonamides, see: Coniglio S, Aramini A, Cesta MC, Colagioia S, Curti R, D’Alessandro F, D’Anniballe G, D’Elia V, Nano G, Orlando V, Allegretti M. Tetrahedron Lett. 2004; 45: 5375
• 21a Sheldrick GM. Acta Crystallogr., Sect. A 2015; 71: 3
• 21b Sheldrick GM. Acta Crystallogr., Sect. C 2015; 71: 3
• 22 Mercury, Version 3.10.1 . Cambridge Crystallographic Data Centre; Cambridge: 2001–2018
• 23 Farrugia LJ. J. Appl. Crystallogr. 2012; 45: 849
• 24 CCDC-1973045 (trans-2a), 1973051 (2i), and 1973055 (8a) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures. See also the Supporting Information.