Medium-Ring Nitrogen Heterocycles through Migratory Ring Expansion of Metalated Ureas
Jessica E. Hall
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS UK
Search for more papers by this authorDr. Johnathan V. Matlock
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS UK
Search for more papers by this authorDr. John W. Ward
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS UK
Search for more papers by this authorKatharine V. Gray
School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL UK
Search for more papers by this authorCorresponding Author
Prof. Jonathan Clayden
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS UK
Search for more papers by this authorJessica E. Hall
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS UK
Search for more papers by this authorDr. Johnathan V. Matlock
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS UK
Search for more papers by this authorDr. John W. Ward
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS UK
Search for more papers by this authorKatharine V. Gray
School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL UK
Search for more papers by this authorCorresponding Author
Prof. Jonathan Clayden
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS UK
Search for more papers by this authorAbstract
Simple benzo-fused nitrogen heterocycles (indolines, tetrahydroquinolines, and their homologues) undergo migratory ring expansion through deprotonation of their benzylic urea derivatives with lithium diisopropylamide (LDA) in the presence of N,N′-dimethylpropylideneurea (DMPU). The products of the reactions are benzodiazepines, benzodiazocines, and their homologues, with ring sizes of 8–12. The reactions tolerate a range of substituent patterns and types, and may exhibit enantiospecificity or diastereoselectivity. Considerable complexity is rapidly generated in an efficient synthesis of these otherwise difficult-to-obtain medium-ring nitrogen heterocycles.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| ange201605714-sup-0001-misc_information.pdf11.1 MB | Supplementary |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1G. Illuminati, L. Mandolini, Acc. Chem. Res. 1981, 14, 95–102.
- 2A. Hussain, S. K. Yousuf, D. Mukherjee, RSC Adv. 2014, 4, 43241–43257 and references cited therein.
- 3E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57, 10257–10274.
- 4Selected methods for the synthesis of medium-sized rings
- 4aA. Klapars, S. Parris, K. W. Anderson, S. L. Buchwald, J. Am. Chem. Soc. 2004, 126, 3529–3533;
- 4bL. Yet, Chem. Rev. 2000, 100, 2963–3008;
- 4cS. K. Chattopadhyay, S. Karmakar, T. Biswas, K. C. Majumdar, H. Rahaman, B. Roy, Tetrahedron 2007, 63, 3919–3952;
- 4dT. P. Majhi, B. Achari, P. Chattopadhyay, Heterocycles 2007, 71, 1011–1052;
- 4eM. J. Begley, L. Crombie, D. Haigh, R. C. F. Jones, S. Osborne, R. A. B. Webster, J. Chem. Soc. Perkin Trans. 1 1993, 2027–2046;
- 4fW. Zhao, H. Qian, Z. Li, J. Sun, Angew. Chem. Int. Ed. 2015, 54, 10005–10008; Angew. Chem. 2015, 127, 10143–10146;
- 4gH. Braunschweig, I. Krummenacher, L. Mailander, F. Rauch, Chem. Commun. 2015, 51, 14513–14515;
- 4hZ. Li, A. Kumar, D. D. Vachhani, S. K. Sharma, V. S. Parmar, E. V. Van der Eycken, Eur. J. Org. Chem. 2014, 2084–2091;
- 4iG. Kulsi, A. Ghorai, P. Chattopadhyay, Tetrahedron Lett. 2012, 53, 3619–3622;
- 4jK. C. Majumdar, K. Ray, S. Ganai, Tetrahedron Lett. 2010, 51, 1736–1738;
- 4kK. C. Majumdar, RSC Adv. 2011, 1, 1152–1170;
- 4lÁ. Gyömöre, A. Csámpai, T. Holzbauer, M. Czugler, Tetrahedron 2011, 67, 2979–2990;
- 4mR. A. Bauer, T. A. Wenderski, D. S. Tan, Nat. Chem. Biol. 2013, 9, 21–29;
- 4nT. M. A. Barlow, M. Jida, K. Guillemyn, D. Tourwe, V. Caveliers, S. Ballet, Org. Biomol. Chem. 2016, 14, 4669–4677;
- 4oC. Kitsiou, J. J. Hindes, P. I'Anson, P. Jackson, T. C. Wilson, E. K. Daly, H. R. Felstead, P. Hearnshaw, W. P. Unsworth, Angew Chem. Int. Ed. 2015 , 54, 15794–15798; Angew. Chem. 2015, 127, 16020—16024.
- 5
- 5aG. A. Archer, L. H. Sternbach, Chem. Rev. 1968, 68, 747–784;
- 5bM. E. Welsch, S. A. Snyder, B. R. Stockwell, Curr. Opin. Chem. Biol. 2010, 14, 347–361;
- 5cL. H. Sternbach, J. Med. Chem. 1979, 22, 1–7;
- 5dC. D. Duarte, E. J. Barreiro, C. A. M. Fraga, Mini-Rev. Med. Chem. 2007, 7, 1108–1119.
- 6
- 6aS. Omura, Macrolide Antibiotics: Chemistry, Biology, and Practice, Elsevier Science, Amsterdam, 2002;
- 6bR. D. Norcross, I. Paterson, Chem. Rev. 1995, 95, 2041–2114.
- 7R. M. J. Liskamp, D. T. S. Rijkers, S. E. Bakker, in Modern Supramolecular Chemistry, Wiley-VCH, Weinheim, 2008, pp. 1–27.
10.1002/9783527621484.ch1 Google Scholar
- 8
- 8aJ. Elleraas, J. Ewanicki, T. W. Johnson, N. W. Sach, M. R. Collins, P. F. Richardson, Angew. Chem. Int. Ed. 2016, 55, 3590–3595; Angew. Chem. 2016, 128, 3654–3659;
- 8bP. Ventosa-Andrés, A. La-Venia, C. A. B. Ripoll, L. Hradilová, V. Krchňák, Chem. Eur. J. 2015, 21, 13112–13119;
- 8cA. F. de la Torre, D. G. Rivera, O. Concepción, R. Echemendia, A. G. Correa, M. W. Paixão, J. Org. Chem. 2016, 81, 803–809;
- 8dN. D. P. Atmuri, W. D. Lubell, J. Org. Chem. 2015, 80, 4904–4918;
- 8eL. Huang, L.-X. Dai, S.-L. You, J. Am. Chem. Soc. 2016, 138, 5793–5796;
- 8fR. Doveston, S. Marsden, A. Nelson, Drug Discovery Today 2014, 19, 813–819.
- 9J. Clayden, W. J. Moran, P. J. Edwards, S. R. LaPlante, Angew. Chem. Int. Ed. 2009, 48, 6398–6401; Angew. Chem. 2009, 121, 6516–6520.
- 10
- 10aJ. Clayden, J. Dufour, D. M. Grainger, M. Helliwell, J. Am. Chem. Soc. 2007, 129, 7488–7489;
- 10bJ. Clayden, U. Hennecke, Org. Lett. 2008, 10, 3567–3570;
- 10cR. Bach, J. Clayden, U. Hennecke, Synlett 2009, 421–424;
- 10dD. J. Tetlow, U. Hennecke, J. Raftery, M. J. Waring, D. S. Clarke, J. Clayden, Org. Lett. 2010, 12, 5442–5445;
- 10eD. M. Grainger, A. Campbell Smith, M. A. Vincent, I. H. Hillier, A. E. H. Wheatley, J. Clayden, Eur. J. Org. Chem. 2012, 731–743;
- 10fM. Tait, M. Donnard, A. Minassi, J. Lefranc, B. Bechi, G. Carbone, P. O'Brien, J. Clayden, Org. Lett. 2013, 15, 34–37;
- 10gD. J. Tetlow, M. A. Vincent, I. H. Hillier, J. Clayden, Chem. Commun. 2013, 49, 1548–1550;
- 10hM. B. Tait, S. Butterworth, J. Clayden, Org. Lett. 2015, 17, 1236–1239;
- 10iJ. Maury, J. Clayden, J. Org. Chem. 2015, 80, 10757–10768;
- 10jR. C. Atkinson, D. J. Leonard, J. Maury, D. Castagnolo, N. Volz, J. Clayden, Chem. Commun. 2013, 49, 9734–9736;
- 10kR. C. Atkinson, F. Fernández-Nieto, J. Mas Roselló, J. Clayden, Angew. Chem. Int. Ed. 2015, 54, 8961–8965; Angew. Chem. 2015, 127, 9089–9093;
- 10lN. Volz, J. Clayden, Angew. Chemie Int. Ed. 2011, 50, 12148–12155; Angew. Chem. 2015, 123, 12354–12361.
- 11For related rerrangements of lithiated carbamates see
- 11aP. Zhang, R. E. Gawley, J. Org. Chem. 1993, 58, 3223–3224;
- 11bS. Superchi, N. Sotomayor, G. Miao, B. Joseph, M. G. Campbell, V. Snieckus, Tetrahedron Lett. 1996, 37, 6061–6064;
- 11cG. B. C. A. Slana, M. S. de Azevedo, R. S. C. Lopes, C. C. Lopes, J. N. Cardoso, Beilstein J. Org. Chem. 2006, 2, 1.
- 12
- 12aA. Ahmed, J. Clayden, S. A. Yasin, Chem. Commun. 1999, 231–232;
- 12bJ. Clayden, F. E. Knowles, C. J. Menet, Synlett 2003, 1701–1703;
- 12c“N,N′-Dimethylpropyleneurea”: A. K. Beck, D. Seebach, G. Nikonov, Encyclopedia of Reagents for Organic Synthesis, Wiley, Hoboken, 2012;
- 12dJ. Clayden, F. E. Knowles, C. J. Menet, Tetrahedron Lett. 2003, 44, 3397–3400;
- 12eJ. Clayden, S. Parris, N. Cabedo, A. H. Payne, Angew. Chem. Int. Ed. 2008, 47, 5060–5062; Angew. Chem. 2008, 120, 5138–5140;
- 12fJ. Clayden, W. Farnaby, D. M. Grainger, U. Hennecke, M. Mancinelli, D. J. Tetlow, I. H. Hillier, M. A. Vincent, J. Am. Chem. Soc. 2009, 131, 3410–3411;
- 12gA. M. Fournier, R. A. Brown, W. Farnaby, H. Miyatake-Ondozabal, J. Clayden, Org. Lett. 2010, 12, 2222–2225;
- 12hJ. Clayton, J. Clayden, Tetrahedron Lett. 2011, 52, 2436–2439.
- 13We assume from precedent (see Ref. [10a], and M. A. Vincent, J. Maury, I. H. Hillier, J. Clayden, Eur. J. Org. Chem. 2015, 953–959) that the rearrangement is configurationally retentive. This assumption is supported by the diastereospecific rearrangement of 16 d to 17 d (see Ref. [18]).
- 14M. Qadir, J. Cobb, P. W. Sheldrake, N. Whittall, A. J. P. White, K. K. Hii, P. N. Horton, M. B. Hursthouse, J. Org. Chem. 2005, 70, 1552–1557.
- 15In common with other medium ring nitrogen heterocycles (K. Tomooka, N. Komine, D. Fujiki, T. Nakai, S. Yanagitsuru, J. Am. Chem. Soc. 2005, 127, 12182–12183) some of these compounds (7 b, 7 d, 7 h, 7 i, 11, 15 b, 15 c, 17 c) showed exchange-broadened signals in their NMR spectra.
- 16K. Saito, Y. Shibata, M. Yamanaka, T. Akiyama, J. Am. Chem. Soc. 2013, 135, 11740–11743.
- 17In situ IR and deuteration studies of the deprotonation of the related compound 7 a with either sec-BuLi or LDA at −78 °C allowed us to deduce that under the reaction conditions used for ring expansion no anion is formed at the doubly benzylic position adjacent to N (see SI for further details). The diastereoselectivity is thus under kinetic control and is not the result of epimerisation of the newly formed stereocenter after ring expansion. Further mechanistic studies are under way.
- 18X-ray structures and NMR data for 16 d and 17 d show that this reaction is stereosepecific and retentive. By analogy, and from Ref. [10a] and [13], we assume this is also the case for ring expansion of 8 and 9.
- 19CCDC 1485153-1485165 contain the crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre.
Citing Literature
This is the
German version
of Angewandte Chemie.
Note for articles published since 1962:
Do not cite this version alone.
Take me to the International Edition version with citable page numbers, DOI, and citation export.
We apologize for the inconvenience.
