Synlett 2017; 28(20): 2755-2758
DOI: 10.1055/s-0036-1589049
letter
© Georg Thieme Verlag Stuttgart · New York

A Photochemical Two-Step Formal [5+2] Cycloaddition: A Condensation–Ring-Expansion Approach to Substituted Azepanes

Scott M. Thullena, b, David M. Rubushb, c, Tomislav Rovis*a, b
  • aDepartment of Chemistry, Columbia University, New York, NY 10027, USA   Email: tr2504@columbia.edu
  • bDepartment of Chemistry, Colorado State University, Fort Collins, CO 80523, USA
  • cCurrent Address: Department of Chemistry, Benedictine University, Lisle, IL 60532, USA
We thank NIGMS for support (GM80442)
Further Information

Publication History

Received: 08 March 2017

Accepted after revision: 10 May 2017

Publication Date:
29 June 2017 (eFirst)

Dedicated to our friend and colleague Victor Snieckus on the occasion of his 80th birthday.

Abstract

Seven-membered nitrogen-containing heterocycles are considerably underrepresented in the literature compared to their five- and six-membered analogues. Herein, we report a relatively understudied photochemical rearrangement of N-vinylpyrrolidinones to azepin-4-ones in good yields. This transformation allows for the conversion of readily available pyrrolidinones and aldehydes to densely functionalized azepane derivatives in a facile two-step procedure.

Supporting Information

 
  • References and Notes

    • 1a Riley DL. van Otterlo WA. L. Heterocycles in Natural Product Synthesis 2011; 537
    • 1b Greger H. Planta Med. 2006; 72: 99
    • 2a Rousseau G. Homsi F. Chem. Soc. Rev. 1997; 26: 453
    • 2b Illuminati G. Mandolini L. Acc. Chem. Res. 1981; 14: 87
    • 3a Vitaku E. Smith BR. Njardarson JT. J. Med. Chem. 2014; 57: 10257
    • 3b Smith BR. Eastman CM. Njardarson JT. J. Med. Chem. 2014; 57: 9764
    • 3c Ilardi EA. Vitaku E. Njardarson JT. J. Med. Chem. 2014; 57: 2832
  • 4 Based on Scifinder search of patents containing synthesis of ‘pyrrolidines’, ‘piperidines’, ‘azepanes’, and ‘azocanes’.
  • 5 Buhr G. DE 2013761, 1970
    • 6a Booker-Milburn KI. Anson CE. Clissold C. Costin NJ. Dainty RF. Murray M. Patel D. Sharpe A. Eur. J. Org. Chem. 2001; 1473
    • 6b Booker-Milburn KI. Dudin LF. Anson CE. Guile SD. Org. Lett. 2001; 3: 3005
    • 6c Roscini C. Cubbage KL. Berry M. Orr-Ewing AJ. Booker-Milburn KI. Angew. Chem. Int. Ed. 2009; 48: 8716
    • 6d Cubbage KL. Orr-Ewing AJ. Booker-Milburn KI. Angew. Chem. Int. Ed. 2009; 48: 2514
    • 6e Lainchbury MD. Medley MI. Taylor PM. Hirst P. Dohle W. Booker-Milburn KI. J. Org. Chem. 2008; 73: 6497
    • 7a Mazzocchi PH. Bowen MJ. Narain NK. J. Am. Chem. Soc. 1977; 99: 7063
    • 7b Mazzocchi PH. Minamikawa S. Bowen MJ. J. Org. Chem. 1978; 43: 3079
    • 7c Mazzocchi PH. Wilson P. Khachik F. Klinger L. Minamikawa S. J. Org. Chem. 1983; 48: 2981
  • 8 Sato Y. Nakai H. Mizoguchi T. Hatanaka Y. Kanaoka Y. J. Am. Chem. Soc. 1976; 98: 2349

    • For the seminal work on amide photo-Fries chemistry, see:
    • 9a Izzo PT. Kende AS. Tetrahedron Lett. 1966; 5731
    • 9b Yang NC. Lenz GR. Tetrahedron Lett. 1967; 4897
    • 9c Hoffmann RW. Eicken KR. Tetrahedron Lett. 1968; 1759
    • 9d Hoffmann RW. Eicken KR. Chem. Ber. 1969; 102: 2987
  • 10 For a recent review on the reactivity of cyclic vinylogous amides as well as other applicable references, see: Seki H. Georg GI. Synlett 2014; 25: 2536

    • For recent reviews on photochemistry in organic synthesis, see:
    • 11a Tanoury GJ. Synthesis 2016; 48: 2009
    • 11b Hoffmann N. Chem. Rev. 2008; 108: 1052
    • 12a Haaf F. Sanner A. Straub F. Polym. J. 1985; 17: 143
    • 12b Güven O. Șen M. Polymer 1991; 32: 2491
    • 12c Yamago S. Chem. Rev. 2009; 109: 5051
  • 13 Song F. Snook JH. Foxman BM. Snider BB. Tetrahedron 1998; 54: 13035
  • 14 Compounds that do not show reactivity in the photochemical rearrangement chemistry are listed in the Supporting Information. Generally speaking, other carbonyl moieties or other UV-reactive moieties seem to be detrimental to the reaction.
  • 15 Shizuka H. Ogiwara T. Morita T. Bull. Chem. Soc. Jpn. 1977; 50: 2067
  • 16 Specifically (from ref. 6c) see Scheme 7.

    • For select approaches to derivatize six-membered ring vinylogous amides, see:
    • 17a Hickmott PW. Tetrahedron 1982; 38: 1975
    • 17b Comins DL. Zeller E. Tetrahedron Lett. 1991; 32: 5889
    • 17c Sěbesta R. Pizzuti MG. Boersma AJ. Minnaard AJ. Feringa BL. Chem. Commun. 2005; 13: 1711
    • 17d Seki H. Georg GI. J. Am. Chem. Soc. 2010; 132: 15512
    • 17e Brimouille R. Bach T. Science 2013; 342: 840
    • 18a Granger BA. Jewett IT. Butler JD. Hua B. Knezevic CE. Parkinson EI. Hergenrother PJ. Martin SF. J. Am. Chem. Soc. 2013; 135: 12984
    • 18b Granger BA. Jewett IT. Butler JD. Martin SF. Tetrahedron 2014; 70: 4094
    • 18c Sakya SM. Flick AC. Coe JW. Gray DL. Liang S. Ferri F. Van Den Berg M. Pouwer K. Tetrahedron Lett. 2012; 53: 723
  • 19 General Procedure An N-vinyl pyrrolidinone was charged in a quartz reaction vessel, under an argon atmosphere, and degassed THF was added (0.01 M) via cannula. The quartz reaction vessel was irradiated in a Rayonet reactor (internal temp. ca. 45 °C) using 254 nm mercury arc lamps until completion. The reaction was then passed through a short silica plug and concentrated in vacuo. The crude product was purified using flash chromatography on silica gel (EtOAc–hexanes or MeOH–CH2Cl2).
  • 20 Representative Product 3-Benzyl-1,5,6,7-tetrahydro-4H-azepin-4-one (4a) Compound 4a was obtained using general procedure from vinyl lactam 3a. White solid; 92% yield. 1H NMR (400 MHz, CDCl3): δ = 7.31–7.08 (m, 5 H), 6.76 (d, J = 7.3 Hz, 1 H), 5.61 (s, 1 H), 3.53 (s, 2 H), 3.46–3.36 (m, 2 H), 2.78–2.68 (m, 2 H), 1.99 (m, 2 H). 13C NMR (101 MHz, CDCl3): δ = 198.76, 142.55, 128.61, 128.17, 125.60, 109.74, 47.18, 42.62, 37.00, 22.94. IR (ATR): 3278, 3075, 2929, 1617, 1544, 1405, 1367, 1325, 1234, 1159, 1108, 1066 cm–1. Rf = 0.15 (85:15 EtOAc–hexanes). LRMS (ESI+APCI): m/z [M + H]+ calcd for [C13H16NO]+: 202.28; found: 202.4.