Organic Letters
Letter
Table 4. Optimization of the Brønsted Acid-Catalyzed
Transfer Hydrogenation of Alkenes
Scheme 2. Transfer Hydrogenation of 1-Phenylcyclohex-1-
ene
a
temperature and prolonged reaction time, offering little
advantage over established protocols (aside from the separation
of the pyridine waste). However, the use of cyclohexa-1,4-diene
and methylated congeners thereof makes the ambient-temper-
ature hydrogenation of structurally9 and electronically unbiased
alkenes possible. The Hantzsch dihydropyridine fails to react
here whereas the hydrocarbon-based dihydrogen sources
cleanly convert those alkenes into alkanes, even in the presence
of the rather weak Brønsted acid TsOH.
entry
surrogate
Brønsted acid
mol %
conv (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1b
1c
2
C6F5CO2H
Ph2P(O)OH
TsOH
10
10
10
10
10
10
10
10
5.0
93
TfOH
92
Tf2NH
quant
97
Tf2NH
Tf2NH
quant
Tf2NH
b
1a
Tf2NH
quant (99)
ASSOCIATED CONTENT
a
■
Determined by GLC analysis with reference to starting material.
Isolated yield after flash chromatography on silica gel in parentheses.
S
b
* Supporting Information
The Supporting Information is available free of charge on the
Several 1,1-disubstituted alkenes were successfully subjected
to the optimized procedure (29−36 → 37−44, Table 5). As
General procedures, experimental details, characteriza-
1
tion data, and H, 13C, and 19F NMR spectra for all
Table 5. Tf2NH-Catalyzed Transfer Hydrogenation of 1,1-
Disubstituted Alkenes
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
a
entry
alkene
R1
R2
alkane
yield (%)
1
2
3
4
5
6
7
8
29
30
31
32
33
34
35
36
4-FC6H4
Ph
4-FC6H4
4-BrC6H4
4-MeOC6H4
Me
37
38
39
40
41
42
43
44
96
99
71
ACKNOWLEDGMENTS
■
This research was supported by the Cluster of Excellence
Unifying Concepts in Catalysis of the Deutsche Forschungsge-
meinschaft (EXC 314/2). M.O. is indebted to the Einstein
Foundation (Berlin) for an endowed professorship.
Ph
b
Ph
41
b
Ph
iPr
99
Ph
Cy
99
b
Me
Cy
nHept
Cy
57
b
REFERENCES
■
96
(1) Wang, D.; Astruc, D. Chem. Rev. 2015, 115, 6621−6686.
(2) Chatterjee, I.; Oestreich, M. Angew. Chem., Int. Ed. 2015, 54,
1965−1968.
a
b
Isolated yield after flash chromatography on silica gel. Determined
by 1H NMR spectroscopy with 1,3,5-trimethoxybenzene as an internal
standard added after the reaction.
(3) Chatterjee, I.; Qu, Z.-W.; Grimme, S.; Oestreich, M. Angew.
Chem., Int. Ed. 2015, 54, 12158−12162.
(4) For pKa values of protonated arenes, see: More O’Ferrall, R. In
Advances in Physical Organic Chemistry, Vol. 44; Richard, J. P., Ed.;
Academic Press: Oxford, U.K., 2010; pp 19−122.
before in the imine case (cf. 9 → 14, Table 2, entry 3), an
electron-donating methoxy group was detrimental to the
hydride affinity of the carbenium ion intermediate; however,
the isolated yield remained good (31 → 39, entry 3). Sterically
less hindered alkenes with a methyl group were susceptible to
thermoneutral dimerization3 (32 → 40 and 35 → 43, entries 4
and 7); we had made the same observation in the B(C6F5)3-
catalyzed transfer hydrogenation.3 Generally, the results of the
Brønsted acid catalysis compared well with those of the
B(C6F5)3 catalysis.3 A trisubstituted alkene was also hydro-
genated in high yield (45 → 46, Scheme 2). However, α-olefins
and 1,2-disubstituted alkenes did not work.
(5) Lefranc, A.; Qu, Z.-W.; Grimme, S.; Oestreich, M. Chem.Eur. J.
(6) For leading reviews, see: (a) Zheng, C.; You, S.-L. Chem. Soc. Rev.
2012, 41, 2498−2518. (b) Ouellet, S. G.; Walji, A. M.; MacMillan, D
W. C. Acc. Chem. Res. 2007, 40, 1327−1339.
(7) For a general review, see: (a) Akiyama, T.; Mori, K. Chem. Rev.
2015, 115, 9277−9306. For reviews of asymmetric Brønsted acid
catalysis, see: (b) Parmar, D.; Sugiono, E.; Raja, S.; Rueping, M. Chem.
Rev. 2014, 114, 9047−9153. (c) Rueping, M.; Sugiono, E.; Schoepke,
F. R. Synlett 2010, 852−865. (d) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv.
Synth. Catal. 2006, 348, 999−1010.
(8) Selected examples of Brønsted acid-catalyzed transfer hydro-
genation using Hantzsch dihydropyridines: (a) Rueping, M.; Sugiono,
E.; Azap, C.; Theissmann, T.; Bolte, M. Org. Lett. 2005, 7, 3781−3783.
(b) Hoffmann, S.; Seayad, A. M.; List, B. Angew. Chem., Int. Ed. 2005,
We demonstrated here that cyclohexa-1,4-dienes are viable
alternatives to Hantzsch dihydropyridines in Brønsted acid-
catalyzed transfer hydrogenation. The reduction of imines,
including examples of reductive amination, require a high
C
Org. Lett. XXXX, XXX, XXX−XXX