Catalytic Asymmetric Construction of Azabicyclo[2.2.1]heptanes Bearing Two Quaternary Stereogenic Centers via Silver(I)-Catalyzed 1,3-Dipolar Cyclo­addition of Cyclic Azomethine Ylides

Abstract

Ag(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar cycloaddition reaction of cyclic azomethine ylides with N-substituted maleimides has been developed for the efficient construction of azabicyclo[2.2.1]heptanes, a valuable structural motif for drug discovery, in good yields with high diastereoselectivities (up to 16:1 dr) and excellent enantioselectivities (up to 97% ee). The key feature of the present methodology is that two quaternary stereogenic centers were constructed efficiently among the generated four contiguous stereocenters in the annulation process.

Key words

asymmetric catalysis - 1,3-dipolar cycloaddition - silver acetate - cyclic azomethine ylide - quaternary stereocenter

• References and Notes

• 1a Armstrong A, Bhonoah Y, Shanahan SE. J. Org. Chem. 2007; 72: 8019
• 1b Gomez-Sanchez E, Soriano E, Marco-Contelles J. J. Org. Chem. 2008; 73: 6784
• 1c Bexrud J, Lautens M. Org. Lett. 2010; 12: 3160
• 1d Reddy CR, Reddy MD, Haribabu K. Eur. J. Org. Chem. 2012; 6414
• 1e Huang X, Shi H, Ren J, Liu G, Tang Y, Zeng B. Chin. J. Chem. 2012; 30: 1305
• 1f Gonzalez J, Koontz JI, Hodges LM, Nilsson KR, Neely LK, Myers WH, Sabat M, Harman WD. J. Am. Chem. Soc. 1995; 117: 3405
• 2a Rizzi L, Dallanoce C, Matera C, Magrone P, Pucci L, Gotti C, Clementi F, De Amici M. Bioorg. Med. Chem. Lett. 2008; 18: 4651
• 2b Michaud A, Levesque C, Fila M, Morin P, Pelchat N, Chenevert R. Tetrahedron: Asymmetry 2011; 22: 819
• 2c Chen Z, Trudell ML. Chem. Rev. 1996; 96: 1179
• 3 Pfister JR, Rescourio G, Venkatraman MS, Zhang X. U.S. Patent US20130059898, 2013
• 4 Aureggi V, Ehmke V, Wieland J, Schweizer WB, Bernet B, Bur D, Meyer S, Rottmann M, Freymond C, Brun R, Breit B, Diederich F. Chem. Eur. J. 2013; 19: 155
• 5a Szantay C, Kardos-Balogh Z, Molfvai I, Szántay CJr, Temesvari-Major E, Blasko G. Tetrahedron Lett. 1994; 35: 3171
• 5b Avenoza A, Cativiela C, Busto JH, Peregrina JM. Tetrahedron Lett. 1995; 36: 7123
• 5c Robinson PL, Barry CN, Kelly JW, Evans SA. Jr. J. Am. Chem. Soc. 1985; 107: 521
• 5d Nelsen SF, Ippoliti JT, Frigo TB, Petillo PA. J. Am. Chem. Soc. 1989; 111: 1776
• 6a Kotian PL, Carroll FI. Synth. Commun. 1995; 25: 63
• 6b Shafiee A, Hite G. J. Org. Chem. 1968; 33: 3435
• 6c Marchand AP, Allen RW. J. Org. Chem. 1975; 40: 2551
• 6d Larock RC, Hershberger SS, Takagi K, Mitchell MA. J. Org. Chem. 1986; 51: 2450
• 6e Kosugi M, Tamura H, Sano H, Migita T. Tetrahedron 1989; 45: 961
• 6f Arcadi A, Marinelli F, Bernocchi E, Cacchi S, Ortar G. J. Organomet. Chem. 1989; 368: 249
• 6g Clayton SC, Regan AC. Tetrahedron Lett. 1993; 34: 7493
• 7 Hernandez A, Marcos M, Rapoport H. J. Org. Chem. 1995; 60: 2683
• 8a Huisgen R, Gotthardt H, Bayer HO. Tetrahedron Lett. 1964; 481
• 8b Gotthardt H, Huisgen R, Bayer HO. J. Am. Chem. Soc. 1970; 92: 4340
• 8c Mkairi A, Hamelin J. Tetrahedron Lett. 1987; 28: 1397
• 8d Pandey G, Lakshmajah G, Ghatak A. Tetrahedron Lett. 1993; 34: 7301
• 9 During the preparation of this manuscript, Waldmann and co-workers reported Cu(I)-catalyzed asymmetric 1,3-dipolar cycloaddition utilizing the 1,3-fused cyclic azomethine ylides substrates. See: Narayan R, Bauer JO, Strohmann C, Antonchick AP, Waldmann H. Angew. Chem. Int. Ed. 2013; 52: 12892
• 10a Stavinoha JL, Mariano PS, Leone-Bay A, Swanson R, Bracken C. J. Am. Chem. Soc. 1981; 103: 3148
• 10b Zaima T, Matsuno C, Matsunaga Y. J. Heterocycl. Chem. 1984; 21: 445
• 10c Zaima T, Matsuno C. J. Heterocycl. Chem. 1983; 20: 1

For recent reviews about 1,3-dipolar cycloaddition reactions of azomethine ylides, see:
• 11a Nájera C, Sansano JM. Angew. Chem. Int. Ed. 2005; 44: 6272
• 11b Álvarez-Corral M, Muñoz-Dorado M, Rodríguez-García I. Chem. Rev. 2008; 108: 3174
• 11c Stanley LM, Sibi MP. Chem. Rev. 2008; 108: 2887
• 11d Engels B, Christl M. Angew. Chem. Int. Ed. 2009; 48: 7968
• 11e Adrio J, Carretero JC. Chem. Commun. 2011; 47: 6784
• 11f Yu J, Shi F, Gong L.-Z. Acc. Chem. Res. 2011; 44: 1156
• 11g Chen Q.-A, Wang D.-S, Zhou Y.-G. Chem. Commun. 2010; 46: 4043
• 12a Cabrera S, Arrayas GR, Carretero JC. J. Am. Chem. Soc. 2005; 127: 16394
• 12b Tsubogo T, Saito S, Seki K, Yamashita Y, Kobayashi S. J. Am. Chem. Soc. 2008; 130: 13321
• 12c Saito S, Tsubogo T, Kobayashi S. J. Am. Chem. Soc. 2007; 129: 5364
• 12d Imae K, Konno T, Ogata K, Fukuzawa S.-I. Org. Lett. 2012; 14: 4410
• 12e Xue M.-X, Zhang X.-M, Gong L.-Z. Synlett 2008; 691
• 12f Wang C.-J, Liang G, Xue Z.-Y, Gao F. J. Am. Chem. Soc. 2008; 130: 17250
• 12g Wang C.-J, Xue Z.-Y, Liang G, Lu Z. Chem. Commun. 2009; 2905
• 13a Isis I, Schofield CJ, Hamed RB, Batchelar ET, Ducho C. PCT Int. Patent WO2010046713A2, 2010
• 13b Hamed RB, Henry L, Gomez-Castellanos JR, Mecinovic J, Ducho C, Sorensen JL, Claridge TD, Schofield CJ. J. Am. Chem. Soc. 2012; 134: 471
• 14a Tong M.-C, Li J, Tao H.-Y, Li Y.-X, Wang C.-J. Chem. Eur. J. 2011; 17: 12922
• 14b Liu T.-L, He Z.-L, Tao H.-Y, Cai Y.-P, Wang C.-J. Chem. Commun. 2011; 47: 2616
• 14c Liu K, Teng H.-L, Yao L, Tao H.-Y, Wang C.-J. Org. Lett. 2013; 15: 2250
• 15a He Z.-L, Teng H.-L, Wang C.-J. Angew. Chem. Int. Ed. 2013; 52: 2934
• 15b Xue Z.-Y, Li Q.-H, Tao H.-Y, Wang C.-J. J. Am. Chem. Soc. 2011; 133: 11757
• 15c Liu T.-L, Xue Z.-Y, Tao H.-Y, Wang C.-J. Org. Biomol. Chem. 2011; 9: 1980
• 15d Xue Z.-Y, Fang X, Wang C.-J. Org. Biomol. Chem. 2011; 9: 3622
• 15e Li Q.-H, Wei L, Wang C.-J. J. Am. Chem. Soc. 2014; 136: 8685
• 15f Yan D, Li Q, Wang C.-J. Chin. J. Chem. 2012; 30: 2714
• 16 Typical Experimental Procedure for the Synthesis of (3aS,4R,7R,7aR)-Methyl 1,3-Dioxo-2,7-diphenyloctahydro-1H-4,7-epiminoisoindole-4-carboxylate (3a): Under an argon atmosphere (S)-TF-BiphamPhos L2 (6.0 mg, 0.0075 mmol) and AgOAc (1.2 mg, 0.007 mmol) were dissolved in CH₂Cl₂ (2 mL), and stirred at r.t. for about 1 h. Then, the cyclic imino ester 1a (0.23 mmol), K₂CO₃ (0.04 mmol) and N-substituted maleimides 2a (0.35 mmol) were added sequentially. Once starting material was consumed (monitored by TLC), the mixture was filtered through celite and the filtrate was concentrated to dryness. The crude product was analyzed by ¹H NMR to determine the exo/endo ratio (16:1). Column chromatographic purification of the crude mass on silica gel (EtOAc–petroleum ether, 1:3) gave 3a (80% yield) as a white solid, which was then directly analyzed by chiral HPLC to determine the enantiomeric excess. Compounds 3a–m were prepared by following a similar procedure. Data for 3a: [α]²⁵ _D –53.5 (c = 1.0, CHCl₃). ¹H NMR (300 MHz, CDCl₃, TMS): δ = 7.31–7.47 (m, 8 H), 7.19–7.22 (m, 2 H), 3.89 (s, 3 H), 3.43 (d, J = 6.9 Hz, 1 H), 3.17 (d, J = 6.9 Hz, 1 H), 2.40–2.49 (m, 1 H), 2.24–2.32 (m, 1 H), 2.04–2.13 (m, 1 H), 1.90–1.98 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃, TMS): δ = 35.25, 38.42, 52.32, 52.45, 53.23, 70.62, 72.29, 126.10, 127.82, 128.28, 128.86, 131.67, 137.92, 170.80, 173.58, 174.66. The enantioselectivity (97% ee) was determined by HPLC (Chiralcel AS-H; i-PrOH–hexane, 30:70; flow rate: 1.0 mL/min, λ = 220 nm); t _R = 12.55 and 16.89 min. HRMS: m/z calcd [M + H⁺] for [C₂₂H₂₀N₂O₄ + H⁺]: 377.1501; found: 377.1493.
• 17 Co-crystal data for (3aS,4R,7R,7aR)-3b and CH₂Cl₂ (1:1): C₂₃H₂₁Cl₃N₂O₄, M _r = 495.77, T = 296 K, monoclinic, space group P2(1), a = 10.3864(14), b = 9.6576(13), c = 11.8090(16) Å, V = 1179.8(3) ų, Z = 2, 7791 reflections measured, 4747 unique (R _int = 0.0632) which were used in all calculations. The final wR ₂ = 0.1674 (all data), Flack χ = 0.07(11). CCDC 977862 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/ retrieving.html [or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB21EZ, UK; fax: [phone]; or [e-mail]].