Organic Letters
Letter
Shields, B. J.; Liu, J.; Williams, M. J.; Zacuto, M. J.; Doyle, A. G. Angew.
Chem., Int. Ed. 2017, 56, 7191−7194.
coordinated imine 23 to give radical cation 24, which is reduced
by the TPP radical formed in the oxidation step.20 These
studies provide further evidence that Lewis acid additives can
expand the range of overall redox neutral reactions performed
under photocatalytic conditions.4,21
In summary, we have documented the synthesis of saturated
N-heterocycles including general conditions for the photo-
catalytic preparation of morpholines and thiomorpholines
under continuous flow conditions and Lewis acid assisted
photoredox catalysis. Further increasing the attractiveness of
this overall approach is the streamlined synthesis of novel SLAP
reagents by aminoetherification of olefins. Further advances in
both of these catalytic methods will expand access to
stereodefined, substituted N-heterocycles for drug discovery
and development.
(2) Previous nonphotoredox studies by our group: (a) Vo, C.-V.;
Mikutis, G.; Bode, J. W. Angew. Chem., Int. Ed. 2013, 52, 1705−1708.
(b) Luescher, M. U.; Vo, C.-V.; Bode, J. W. Org. Lett. 2014, 16, 1236−
1239. (c) Vo, C.-V.; Luescher, M. U.; Bode, J. W. Nat. Chem. 2014, 6,
310−314. (d) Geoghegan, K.; Bode, J. W. Org. Lett. 2015, 17, 1934−
1937. (e) Luescher, M. U.; Bode, J. W. Angew. Chem., Int. Ed. 2015, 54,
10884−10888. (f) Jackl, M. K.; Kreituss, I.; Bode, J. W. Org. Lett. 2016,
18, 1713−1715. (g) Luescher, M. U.; Bode, J. W. Org. Lett. 2016, 18,
2652−2655.
(3) Hsieh, S.-Y.; Bode, J. W. Org. Lett. 2016, 18, 2098−2101.
(4) Hsieh, S.-Y.; Bode, J. W. ACS Cent. Sci. 2017, 3, 66−72.
(5) Slinker, J. D.; Gorodetsky, A. A.; Lowry, M. S.; Wang, J.; Parker,
S.; Rohl, R.; Bernhard, S.; Malliaras, G. G. J. Am. Chem. Soc. 2004, 126,
2763−2767.
(6) Lowry, M. S.; Goldsmith, J. I.; Slinker, J. D.; Rohl, R.; Pascal, R.
A.; Malliaras, G. G.; Bernhard, S. Chem. Mater. 2005, 17, 5712−5719.
(7) Yoshida, J.-i.; Maekawa, T.; Murata, T.; Matsunaga, S.; Isoe, S. J.
Am. Chem. Soc. 1990, 112, 1962−1970.
(8) Yoshida, J.-i. Top. Curr. Chem. 1994, 170, 39−81.
(9) Yoshida, J.-i.; Kataoka, K.; Horcajada, R.; Nagaki, A. Chem. Rev.
2008, 108, 2265−2299.
(10) Nicewicz, D. A.; Nguyen, T. M. ACS Catal. 2014, 4, 355−360.
(11) These values are converted from +2.53 V vs NHE and −0.13 V
vs NHE, see: Martiny, M.; Steckhan, E.; Esch, T. Chem. Ber. 1993, 126,
1671−1682.
(12) This value is converted from −1.46 V vs NHE, see: Jonsson, M.;
Wayner, D. D. M.; Lusztyk, J. J. Phys. Chem. 1996, 100, 17539−17543.
(13) Selected literature on flow chemistry: (a) Su, Y.; Straathof, N. J.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
Crystallographic data for 18-b (CIF)
Experimental procedures and characterization data
AUTHOR INFORMATION
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W.; Hessel, V.; Noel, T. Chem. - Eur. J. 2014, 20, 10562−10589.
̈
Corresponding Author
ORCID
(b) Guerra, J.; Cantilloa, D.; Kappe, C. O. Catal. Sci. Technol. 2016, 6,
4695−4699. (c) Lima, F.; Kabeshov, M. A.; Tran, D. N.; Battilocchio,
C.; Sedelmeier, J.; Sedelmeier, G.; Schenkel, B.; Ley, S. V. Angew.
Chem., Int. Ed. 2016, 55, 14085−14089. (d) Straathof, N. J. W.;
Notes
Tegelbeckers, B. J. P.; Hessel, V.; Wang, X.; Noel, T. Chem. Sci. 2014,
̈
5, 4768−4773. (e) Tucker, J. W.; Zhang, Y.; Jamison, T. F.;
Stephenson, C. R. J. Angew. Chem., Int. Ed. 2012, 51, 4144−4147.
(f) Cambie, D.; Bottecchia, C.; Straathof, N. J. W.; Hessel, V.; Noel, T.
̈
The authors declare no competing financial interest.
Chem. Rev. 2016, 116, 1027−10341.
(14) Legnani, L.; Morandi, B. Angew. Chem., Int. Ed. 2016, 55, 2248−
ACKNOWLEDGMENTS
■
2251.
Financial support was provided by the European Research
Council (ERC Starting Grant 306793 − CASAA). We thank
the LOC Mass Spectrometry Service, the LOC NMR Service
and the Small Molecule Crystallography Center of ETH Zurich
for the X-ray measurement. We want to thank Dr. Benedikt
Wanner (ETH Zurich) and Dr. Anastasios Polyzos (University
of Melbourne) for the construction of the flow-reactor, Dr.
Sheng-Ying Hsieh (ETH Zurich) for preliminary experiments
(15) Miranda, M. A.; Garcia, H. Chem. Rev. 1994, 94, 1063−1089.
(16) Ramamurthy, P.; Morlet-Savary, J. F.; Fouassier, J. P. J. Chem.
Soc., Faraday Trans. 1993, 89, 465−469.
(17) This value is converted from +1.34 V vs NHE, see: Jonsson, M.;
Wayner, D. D. M.; Lusztyk, J. J. Phys. Chem. 1996, 100, 17539−17543.
(18) Jonsson, M.; Lind, J.; Merenyi, G.; Eriksen, T. E. J. Chem. Soc.,
Perkin Trans. 2 1995, 61−65.
(19) Gubta, P.; Rouf, A.; Shah, B. A.; Mukherjee, D.; Taneja, S. C.
Synth. Commun. 2013, 43, 505−519.
and Dr. Michael Luscher (ETH Zurich) and Dr. Reinhard Otto
̈
(20) An alternative diradical mechanism was considered, starting with
the reduction of the activated imine by PC*+ followed by oxidation of
the α-trimethylsilyl ethers by PC•++ to generate the diradical species.
While possible, we consider it less likely on the basis of both kinetic
considerations and the poor reduction ability of the TPP*+.
(21) (a) Fukuzumi, S.; Jung, J.; Min Lee, Y.; Nam, W. Asian J. Org.
Chem. 2017, 6, 397−409. (b) Renaud, P.; Gerster, M. Angew. Chem.,
Int. Ed. 1998, 37, 2562−2579.
Kissner (ETH Zurich) for helpful discussions. B. M. and L. L.
acknowledge the Max-Planck-Society, the Max-Planck-Institut
fur Kohlenforschung, the Otto Rohm Gedachtnisstiftung and
̈
̈
̈
the Fonds der Chemischen Industrie for financial support.
REFERENCES
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