10.1002/anie.201800667
Angewandte Chemie International Edition
COMMUNICATION
urea radical cyclization due to the greater steric demands of the
proximal ethyl groups.[19] As expected, anti-transition states were
found to be the lowest in energy in all cases.[5]
Keywords: urea • radical • cyclization • samarium • nitrogen
heterocycles
A proposed mechanism for the urea radical cyclization is shown
in Scheme 8. SET to substrates 1 and 4 gives delocalized
radical anion 6. When R’ is larger than Me, carbon-carbon bond
formation takes place at what was the carbon of the urea
carbonyl and 5-exo-trig cyclization gives the corresponding
bicyclic Sm(III) alkoxide intermediates 7 (Scheme 8).
[1]
[2]
a) L. Yin, J. Liebscher, Chem. Rev. 2007, 107, 133–173; b) N.
Rodríguez, L. J. Goossen, Chem. Soc. Rev. 2011, 40, 5030–5048; c) M.
Fagnoni, D. Dondi, D. Ravelli, A. Albini, Chem. Rev. 2007, 107, 2725–
2756; d) J. Choi, G. C. Fu, Science 2017, 356, eaaf7230.
a) J. Iqbal, B. Bhatia, N. K. Nayyar, Chem. Rev. 1994, 94, 519–564; b)
G. Bar, A. F. Parsons, Chem. Soc. Rev. 2003, 32, 251; c) M. Yan, J. C.
Lo, J. T. Edwards, P. S. Baran, J. Am. Chem. Soc. 2016, 138, 12692–
12714; d) A. Studer, D. P. Curran, Nat. Chem. 2014, 6, 765–773; e) A.
Studer, D. P. Curran, Angew. Chem., Int. Ed. 2016, 55, 58–102; Angew.
Chem. 2016, 128, 58-106.
O
O
Me
N
R'
R'
Ar
[3]
a) M. P. Plesniak, H.-M. Huang, D. J. Procter, Nat. Rev. Chem. 2017, 1,
0077; b) E. A. Anderson, Org. Biomol. Chem. 2011, 9, 3997; c) K. C.
Nicolaou, J. S. Chen, Chem. Soc. Rev. 2009, 38, 2993; d) K. C.
Nicolaou, D. J. Edmonds, P. G. Bulger, Angew. Chem., Int. Ed. 2006,
45, 7134–7186; e) K. K. Wang, Chem. Rev. 1996, 96, 207–222; f) L. F.
Tietze, Chem. Rev. 1996, 96, 115–136.
N
3'
1 or 4
1 e
–H2O R = Me
R
in tBuOH
O
O
O
R
N
SmIII
O
SmIII
Ar
N
N
7
R'
R'
R'
5-exo-trig
1 e, H
O
Ar
[4]
[5]
a) K. N. Lee, M.-Y. Ngai, Chem. Commun. 2017, 53, 13093–13112; b)
J. Cossy, D. Belotti, Tetrahedron 2006, 62, 6459–6470; c) A. Gansäuer,
H. Bluhm, Chem. Rev. 2000, 100, 2771–2788.
R'
O
N
6
–H2O
1 e
a) M. Szostak, N. J. Fazakerley, D. Parmar, D. J. Procter, Chem. Rev.
2014, 114, 5959–6039; b) C. Beemelmanns, H.-U. Reissig, Chem. Soc.
Rev. 2011, 40, 2199–2210; c) C. Beemelmanns, H.-U. Reissig, Pure
Appl. Chem. 2011, 83, 507–518; d) K. C. Nicolaou, S. P. Ellery, J. S.
Chen, Angew. Chem., Int. Ed. 2009, 48, 7140–7165; e) R. Flowers, II,
Synlett 2008, 2008, 1427–1439; f) D. J. Edmonds, D. Johnston, D. J.
Procter, Chem. Rev. 2004, 104, 3371–3403; g) G. A. Molander, C. R.
Harris, Chem. Rev. 1996, 96, 307–338.
in H2O
O
Me
O
R
N
H
N
R = Me
R'
R'
R'
Ar
Ar
R'
O
N
N
1 e, H
O
O
3
8
5-exo-trig 1 e, H
R = –(CH2)2CH=CHAr
Ar
Ar
R'
R'
N
[6]
a) Y.-Q. Zhang, E. Vogelsang, Z.-W. Qu, S. Grimme, A. Gansäuer,
Angew. Chem., Int. Ed. 2017, 56, 12654–12657; b) W. Hao, X. Wu, J. Z.
Sun, J. C. Siu, S. N. MacMillan, S. Lin, J. Am. Chem. Soc. 2017, 139,
12141–12144; c) J. Streuff, Chem. Rec. 2014, 14, 1100–1113; d) J.
Streuff, M. Feurer, P. Bichovski, G. Frey, U. Gellrich, Angew. Chem., Int.
Ed. 2012, 51, 8661–8664; e) A. Fürstner, B. Bogdanović, Angew.
Chem., Int. Ed. 1996, 35, 2442–2469; f) E. C. Gentry, R. R. Knowles,
Acc. Chem. Res. 2016, 49, 1546–1556; g) A. G. Amador, E. M.
Sherbrook, T. P. Yoon, J. Am. Chem. Soc. 2016, 138, 4722–4725; h) H.
Yayla, R. Knowles, Synlett 2014, 25, 2819–2826; i) J. Du, K. L. Skubi,
D. M. Schultz, T. P. Yoon, Science 2014, 344, 392–396; j) L. J. Rono, H.
G. Yayla, D. Y. Wang, M. F. Armstrong, R. R. Knowles, J. Am. Chem.
Soc. 2013, 135, 17735–17738; k) T. Shono, N. Kise, T. Fujimoto, N.
Tominaga, H. Morita, J. Org. Chem. 1992, 57, 7175–7187.
N
O
5
Scheme 8. Proposed mechanism for the urea radical cyclizations.
When tBuOH is used as the proton source, bicyclic enediamines
3’ are obtained upon elimination. In contrast, when H2O is used,
the more reducing reagent system forms aminal radicals 8 and
further reduction and protonation delivers bicyclic aminals 3.
When the R group in 8 contains a radical trap, the aminal
radicals undergo cyclization to give cascade products 5, after
further reduction and protonation.
In summary, ketyl-type radical anions derived from the urea
carbonyl by reductive SET undergo, intramolecular carbon-
carbon bond formation. Depending upon the proton source used
in the radical reactions, a chemoselective switch between
reaction pathways delivers two important heterobicyclic scaffolds.
Computational studies have been employed to explore the
natural of the radical anion intermediates and their selective
radical cyclization. Furthermore, radical cyclization cascades
involving radicals derived from ureas by SET deliver unusual
spirocyclic aminal architectures.
[7]
Selected recent examples: a) N. J. Fazakerley, M. D. Helm, D. J.
Procter, Chem. -Eur. J. 2013, 19, 6718–6723; b) M. D. Helm, M. Daâ
Silva, D. Sucunza, T. J. â. K. Findley, D. J. Procter, Angew. Chem., Int.
Ed. 2009, 48, 9315–9317; c) S. E. Reisman, J. M. Ready, M. M. Weiss,
A. Hasuoka, M. Hirata, K. Tamaki, T. V Ovaska, C. J. Smith, J. L. Wood,
J. Am. Chem. Soc. 2008, 130, 2087–2100; d) J. Y. Cha, J. T. S.
Yeoman, S. E. Reisman, J. Am. Chem. Soc. 2011, 133, 14964–14967;
e) J. T. S. Yeoman, V. W. Mak, S. E. Reisman, J. Am. Chem. Soc.
2013, 135, 11764–11767; f) K. C. Nicolaou, A. Li, D. J. Edmonds, G. S.
Tria, S. P. Ellery, J. Am. Chem. Soc. 2009, 131, 16905–16918; g) T. Xu,
C. C. Li, Z. Yang, Org. Lett. 2011, 13, 2630–2633; h) G. K. Murphy, T.
Shirahata, N. Hama, A. Bedermann, P. Dong, T. C. McMahon, B. M.
Twenter, D. A. Spiegel, I. M. McDonald, N. Taniguchi, et al., J. Org.
Chem. 2013, 78, 477–489; i) C. Beemelmanns, H.-U. Reissig, Angew.
Chem., Int. Ed. 2010, 49, 8021–8025; j) Z. Li, M. Nakashige, W. J.
Chain, J. Am. Chem. Soc. 2011, 133, 6553–6556.
Acknowledgements
[8]
a) X. Just-Baringo, D. J. Procter, Acc. Chem. Res. 2015, 48, 1263–
1275. Selected examples: b) K. D. Collins, J. M. Oliveira, G. Guazzelli,
B. Sautier, S. De Grazia, H. Matsubara, M. Helliwell, D. J. Procter,
Chem. -Eur. J. 2010, 16, 10240–10249; c) B. Sautier, S. E. Lyons, M. R.
Webb, D. J. Procter, Org. Lett. 2012, 14, 146–149; d) D. Parmar, H.
We thank the EPSRC (EPSRC Established Career Fellowship to
D.J.P.), the Leverhulme Trust (Research Fellowship to D.J.P.),
and the University of Manchester (President’s Scholarship to
H.H.) for funding.
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