Organic Process Research & Development
Communication
L.; Bogdan, A. R.; McQuade, D. T. Chem. Rev. 2007, 107, 2300−2318.
(e) Yoshida, J. I.; Nagaki, A.; Yamada, T. Chem.Eur. J. 2008, 14,
7450−7459. (f) Hessel, V. Chem. End. Technol. 2009, 32, 1655−1681.
(g) Webb, D.; Jamison, T. F. Chem. Sci. 2010, 1, 675−680.
(h) Hartman, R. L.; McMullen, J. P.; Jensen, K. F. Angew. Chem.,
Int. Ed. 2011, 50, 7502−7519. (i) Ley, S. V. Chem. Rec. 2012, 12, 378−
390. (j) Wegner, J.; Ceylan, S.; Kirschning, A. Adv. Synth. Catal. 2012,
354, 17−57. (k) McQuade, D. T.; Seeberger, P. H. J. Org. Chem. 2013,
78, 6384−6389.
MeOH. After silica gel column chromatography (1:5 ethyl
acetate−n-hexane), pure N-methylcyclohexyl amine (0.198 g)
1
was obtained as a colorless oil (37%). H NMR: 3.39 (br s,
1H), 2.75 (m, 1H), 2.52 (d, J = 8 Hz, 3H), 2.07 (m, 1H), 1.87
(m, 2H), 1.67 (m, 1H), 1.47−1.15 (m, 6H). Matches literature
data: Neidigh, K. A.; Avery, M. A.; Williamson, J. S.;
Bhattacharyya, S. J. Chem. Soc., Perkins Trans. 1 1998, 2527−
2532.
(2) For select examples, see: (a) Kirschning, A.; Jas, G. Top. Curr.
Chem. 2004, 242, 209−239. (b) Chinnusamy, T.; Yudha, S. S.; Hager,
M.; Kretmeier, P.; Reiser, O. ChemSusChem 2012, 5, 247−255.
(c) Bogdan, A. R.; Mason, B. P.; Sylvester, K. T.; McQuade, D. T.
Angew. Chem., Int. Ed. 2007, 46, 1698−1701. (d) Mak, X. Y.; Laurino,
4-((Methylamino)methyl)benzonitrile. 4-((Methylamino)-
methyl)benzonitrile was prepared according to general
procedure for reductive amination with p-cyanobenzaldehyde
(0.446 g) dissolved in a mixture of MeOH (1.1 mL) and THF
(2.84 mL), and to methyl amine (3.73 mL of a 2 M THF
solution) was added 0.2 mL of MeOH. After silica gel column
chromatography (1:3 ethyl acetate−n-hexane), pure N-methyl-
p-cyanobenyl amine (0.227 g) was obtained as a colorless oil
P.; Seeberger, P. H. Beilstein J. Org. Chem. 2009, 5, 19−30. (e) Noel,
̈
T.; Buchwald, S. L. Chem. Soc. Rev. 2011, 40, 5010−5029.
(3) Roberge, D. M.; Ducry, L.; Bieler, N.; Cretton, P.; Zimmermann,
B. Chem. Eng. Technol. 2005, 28, 318−323.
(4) (a) Horie, T.; Sumino, M.; Tanaka, T.; Matsushita, Y.; Ichimura,
T.; Yoshida, J.-I. Org. Process. Res. Dev. 2010, 14, 405−410.
(b) Sedelmeier, J.; Ley, S. V.; Baxendale, I. R.; Baumann, M. Org.
Lett. 2010, 12, 3618−3621. (c) Noel, T.; Naber, J. R.; Hartman, R. L.;
̈
1
McMullen, J. P.; Jensen, K.; Buchwald, S. L. Chem. Sci. 2011, 2, 287−
290. (d) Correia, C. A.; McQuade, D. T.; Seeberger, P. H. Adv. Synth.
Catal. 2013, 355, 3517−3521.
(45%). H NMR: 7.62 (d, J = 8 Hz, 2H), 7.45 (d, J = 8 Hz,
2H), 3.82 (s, 2H), 2.45 (s, 3H), 1.81 (s, 1H). Matches literature
data: Larkin, J. D.; Frimat, K. A.; Fyles, T. M.; Flower, S. E.;
James, T. D. New. J. Chem. 2010, 34, 2922−2931.
(5) Noel, T.; Maimone, T. J.; Buchwald, S. L. Angew. Chem., Int. Ed.
̈
2011, 50, 8900−8903.
(6) Opalka, S. M.; Longstreet, A. R.; McQuade, D. T. Beilstein J. Org.
Chem. 2011, 7, 1671−1679.
(7) For select recent work using packed columns in flow, see:
(a) Hopkin, M. D.; Baxendale, I. R.; Ley, S. V. Org. Biomol. Chem.
2013, 11, 1822−1839. (b) Ingham, R. J.; Riva, E.; Nikbin, N.;
Baxendale, I. R.; Ley, S. V. Org. Lett. 2012, 14, 3920−3923.
(8) Opalka, S. M.; Park, J. K.; Longstreet, A. R.; McQuade, D. T. Org.
Lett. 2013, 15, 996−999.
(9) (a) Yoon, N. M. Pure Appl. Chem. 1996, 68, 843−848.
(b) Deloux, L.; Srebnik, M. Chem. Rev. 1993, 93, 763−784.
(10) (a) Webb, D.; Jamison, T. F. Org. Lett. 2012, 14, 568−571.
(b) Webb, D.; Jamison, T. F. Org. Lett. 2012, 14, 2465−2467.
(11) Fan, X.; Sans, V.; Yaseneva, P.; Plaza, D. D.; Williams, J.; Lapkin,
A. Org. Process Res. Dev. 2012, 16, 1039−1042.
(12) (a) Kirschning, A.; Monenschein, H.; Wittenberg, R. Angew.
Chem., Int. Ed. 2001, 40, 650−679. For select polymer-supported
borohydride reductions in batch, see (b) Lakouraj, M. M.; Tajbakhsh,
M.; Mahalli, M. S. Monatsh. Chem. 2008, 139, 117−123. (c) Kell, R. J.;
Hodge, P.; Watson, D. Org. Biomol. Chem. 2003, 1, 3238−3243.
(d) Gibson, H. W.; Bailey, F. C. J. Chem. Soc., Chem. Commun. 1977,
815a−815a.
(13) (a) Soloshonok, V. A.; Catt, H. T.; Ono, T. J. Fluorine Chem.
2010, 131, 261−265. For select resin-supported borohydride
reductions in batch, see (b) Srivani, A.; Sai Prasad, P. S.; Lingaiah,
N. Catal. Lett. 2012, 142, 389−396. (c) Fernandes, J. L. N.; de Souza,
M. C.; Brenelli, E. C. S.; Brenelli, J. A. Synthesis 2009, 23, 4058−4062.
(d) Barth, M.; Shah, S. T. A.; Rademann, J. Tetrahedron 2004, 60,
8703−8709. (e) Kirschning, A. J. Prakt. Chem. 2000, 342, 508−511.
(14) Recently, in situ generated ketones have been successfully
reduced in flow using a NaBH4 as a 0.4 m solution in absolute ethanol,
with concommitant cyclization of the alkoxide onto an ester moiety,
see Fagnoni, M.; Bonassi, F.; Palmieri, A.; Protti, S.; Ravelli, D.; Ballini,
R. Adv. Synth. Catal. 2014, 356, 753−758.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Associated H NMR for the synthesized compounds. This
material is available free of charge via the Internet at http://
AUTHOR INFORMATION
Corresponding Author
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the Max Planck Society and the German
Academic Exchange Service (graduate fellowship to S.V.) is
gratefully acknowledged.
ABBREVIATIONS
■
NaBH4, sodium borohydride; NHC, N-heterocyclic carbene;
DIBAL, diisobutylaluminum hydride; LiCl, lithium chloride;
THF, tetrahydrofuran; SiO2, ailica; MeOH, methanol; BnAL,
benzaldehyde; BnOH, benzyl alcohol; Ph, phenyl; NaCNBH3,
sodium cyanoborohydride; n-Pr, n-propyl; SM, starting materi-
al; HPLC, high-performance liquid chromatography; NMR,
nuclear magnetic resonance; UV, ultraviolet; TLC, thin-layer
chromatography; FEP, fluorinated ethylene−propylene copoly-
mer; BPR, back-pressure regulator; Na2SO4, sodium sulfate
(15) Schwartz, D.; Reynolds, R. Microchem. J. 1975, 20, 50−55.
(16) Gyoung, Y. S.; Yoon, N. M.; Jeon, D. H. Bull. Korean Chem. Soc.
1987, 8, 162−165.
REFERENCES
■
(17) (a) Fernandes, J. L. N.; de Souza, M. C.; Brenelli, E. C. S.;
(1) (a) Watts, P.; Haswell, S. J. Chem. Soc. Rev. 2005, 34, 235−246.
(b) Geyer, K.; Codee, J. D.; Seeberger, P. H. Chem.Eur. J. 2006, 12,
8434−8442. (c) Ahmed-Omer, B.; Brandt, J. C.; Wirth, T. Org. Biol.
Chem. 2007, 5, 733−740. (d) Mason, B. P.; Price, K. E.; Steinbacher, J.
Brenelli, J. A. Synthesis 2009, 23, 4058−4068. (b) Gonca̧ lves, R. S. B.;
Pinheiro, A. C.; da Silva, E. T.; da Costa, J. C. S.; Kaiser, C. R.; de
Souza, M. V. N. Synth. Commun. 2011, 41, 1276−1281.
E
dx.doi.org/10.1021/op500310s | Org. Process Res. Dev. XXXX, XXX, XXX−XXX