Visible-Light-Promoted Asymmetric Cross-Dehydrogenative Coupling of Tertiary Amines to Ketones by Synergistic Multiple Catalysis

Article abstract of DOI:10.1002/anie.201700572

Reported herein is an unprecedented photocatalytic asymmetric cross-dehydrogenative coupling reaction between tertiary amines and simple ketones, and it proceeds by synergistic multiple catalysis with substoichiometric amounts of a hydrogen acceptor. This process is enabled by a simple chiral primary amine catalyst through the coupling of a catalytic enamine intermediate and an iminium cation intermediate in situ generated from tetrahydroisoquinoline derivatives by coupled Ru/Co catalysis.

Full text of DOI:10.1002/anie.201700572

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201700572
German Edition: DOI: 10.1002/ange.201700572
Cross-Coupling
Visible-Light-Promoted Asymmetric Cross-Dehydrogenative Coupling
of Tertiary Amines to Ketones by Synergistic Multiple Catalysis
Qi Yang, Long Zhang, Chen Ye, Sanzhong Luo,* Li-Zhu Wu,* and Chen-Ho Tung
Abstract: Reported herein is an unprecedented photocatalytic
asymmetric cross-dehydrogenative coupling reaction between
tertiary amines and simple ketones, and it proceeds by
synergistic multiple catalysis with substoichiometric amounts
of a hydrogen acceptor. This process is enabled by a simple
chiral primary amine catalyst through the coupling of a cata-
lytic enamine intermediate and an iminium cation intermediate
in situ generated from tetrahydroisoquinoline derivatives by
coupled Ru/Co catalysis.
T
he direct cross-dehydrogenative coupling (CDC) of two
3
À
À
C(sp ) H bonds has recently become an enabling C C bond-
formation strategy in synthetic chemistry.[1–4] The develop-
ment of catalytic enantioselective versions has since been
actively pursued to include the asymmetric a-coupling of
carbonyls, thus adding new variants to the fundamental
a-carbonyl chemistry. Despite the advances, the successes
with simple aldehydes and ketones have been rather lim-
ited.[3,4] The elegant contributions from the groups of
Rueping,[4a] Chi,[4f] and Wang[4b,g] have verified the feasibility
of chiral aminocatalysis in facilitating the reactions with
aldehydes and ketones. These reactions were generally
carried out with stoichiometric or excess amounts of strong
oxidants, but the oxidative stability of the aminocatalysts
remain an issue,[4i,5] thus limiting another explorations along
this line (Scheme 1a). To overcome this oxidative constraint,
we explored a tricatalytic hydrogen-transfer strategy for
enantioselective CDC coupling by merging primary amine
catalysis,[5] photocatalysis,[6–8] and cobalt catalysis[9] under
hydrogen-transfer conditions. In this reaction cycle, substoi-
chiometric amounts of a nitro-compound act as the hydrogen
acceptor, and circumvents the need for extra oxidants and
Scheme 1. Direct CDC reaction. a) Oxidative coupling of tertiary
amines to carbonyl compounds. b) Photocatalytic hydrogen-transfer
asymmetric CDC reaction with substoichiometric hydrogen acceptor.
PC=photocatalyst.
avoids the oxidative consumption of the amine catalyst under
harsh oxidation conditions (Scheme 1b). The current strategy
makes possible a wide applicability and distinctive reactivity
for a number of ketones and gives syn-diastereoselectivity for
the reactions with cyclic ketones, which had not been seen in
other asymmetric oxidative Mannich reactions of aldehydes
and ketones.[4f,g]
The asymmetric CDC reaction between N-phenyl-tetra-
hydroisoquinoline (1a) and cyclohexanone (2a) was first
selected as the model reaction. Initial studies involved
reactions with stoichiometric oxidants under either thermal
or photocatalytic conditions, thus giving, unfortunately, either
complicated reaction mixtures or no reaction (see Table S1 in
the Supporting Information). At this point, we explored the
photocatalytic hydrogen-transfer strategy by the combination
with Ru/Co cocatalysts. To our delight, the reaction pro-
ceeded smoothly and we quickly identified an optimal
tricatalytic system involving our chiral primary amine catalyst
and Ru/Co complexes (Table 1, entry 1). Under these reac-
tion conditions, conversion was complete within 24 hours and
the desired product 3aa was obtained with 83% yield, 8.8:1
d.r, and 99% ee (entry 1). Variation of cobalt catalysts
(entries 2 and 3), photocatalysts (entries 4 and 5), primary
amine catalysts (entries 6–9), temperature (entries 10 and 11),
or the ratio between photocatalyst and cobalt catalyst
[*] Q. Yang, Dr. L. Zhang, Prof. Dr. S. Luo
Key Laboratory for Molecular Recognition and Function
Institute of Chemistry, Chinese Academy of Sciences
Beijing, 100190 (China)
and
University of Chinese Academy of Sciences
Beijing, 100049 (China)
E-mail: luosz@iccas.ac.cn
Homepage: http://luosz.iccas.ac.cn
C. Ye, Prof. Dr. L.-Z. Wu, Prof. Dr. C.-H. Tung
Key Laboratory of Photochemical Conversion and Optoelectronic
Materials, Technical Institute of Physics and Chemistry
Chinese Academy of Sciences
(entries 12–14) led to
a decrease in either the yield,
d.r. value, or ee value. When m-NO2C6H4COOH was replaced
by benzoic acid, the yield significantly decreased to 16% with
17% H2 evolution (entry 15). We speculated that
m-NO2C6H4COOH was not only a weak acid additive,
which had been shown to promote enamine formation as we
Beijing 100190 (China)
E-mail: lzwu@mail.ipc.ac.cn
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
http://dx.doi.org/10.1002/anie.201700572.
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Table 1: Screening and optimization.[a]
were essential for the reaction (entries 19–21), as either no
reaction or poor yield was observed in their absence.
Under the optimized reaction conditions, the scope was
then examined. As shown in Scheme 2, tetrahydroisoquino-
lines with variations on the phenyl moiety (R1 and R2
position) were tolerated in the reactions to afford the desired
Entry Variation from standard conditions Yield [%][b] d.r.[c] ee [%][d]
1
2
none
83[e]
8.8:1 99
4.0:1 97
Co(dmgBF2)2(H2O)2 instead of Co- 60
(dmgH)2Cl2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Co(dmgH)2ClPy
Eosin Y
Ir(ppy)3
4b instead of 4a
4c
4d
4e
28C
RT
70
48
8
48
60
73
55
77
73
59
65
81
3.2:1 97
8.2:1 99
8.1:1 98
1:3.0 60
1:2.2 45
1:1.8 25
1:3.6 15
4.2:1 93
3.2:1 78
5.1:1 96
5.4:1 95
5.9:1 98
3.5:1 95
4.3:1 96
6.8:1 97
7.3:1 95
3.4:1 94
[PC]/[Co]=1:10
[PC]/[Co]=2:10
[PC]/[Co]=3:10
40 mol% benzoic acid
40 mol% benzoic acid[g]
in air
Scheme 2. Scope with respect to tetrahydroisoquinolines. For the X-ray
structure of 3ac, the thermal ellipsoids are shown at 30% probabil-
ity.[17]
16[f]
53[h]
58
19
38
trace
n.r.
in air[i]
no Co(dmgH)2Cl2
no Ru(bpy)3Cl2·6H2O
in the dark
syn-Mannich-type adducts with good to excellent diastereo-
and enantioselectivities (3aa–k). The absolute configuration
was determined by single-crystal X-ray diffraction of 3ac (see
Table S3).[17] It was noted that the diastereoselectivity was
opposite to that observed in the study by Wang and co-
workers,[4g] which indicated a distinctive stereocontrol mode.
Other tertiary amines or secondary amines were also
examined, but led to either no desired reactions or compli-
cated reaction mixtures (Scheme S2).
The reaction was not limited to cyclohexanones
(Scheme 3). Tetrahydrothiapyrone and tetrahydropyranone
also served as good nucleophiles in the reaction (3ba–d),
though the products were easy to undergo racemization when
isolated by silica gel column. Meanwhile, the reactions were
successfully applied to other kinds of cyclic ketones in good to
excellent yields with high d.r. and ee values (3be–l), which
were not realizable in previous work.[4] Eosin Y had been
used to replace Ru(bpy)3Cl2·6H2O, and a similar outcome was
obtained by prolonging reaction time (3be–l). Acyclic
ketones had also been examined to give the desired adducts
(3bo–p) with good yields but lower enantioselectivities.
We next explored the desymmetrization process of
4-substituted cyclohexanones. In this reaction, challenges
mainly came from the difficulties in simultaneously control-
ling the diastereo- and enantioselectivities of C2 and remote
C4 position (Scheme 4). To our delight, most of the substrates
gave the desired products in good to excellent yields with high
d.r. and ee values (3ca–cf). The absolute configuration of 3cd
[a] Reaction conditions: 1a (0.1 mmol), 2a (0.3 mmol), 4a/HOTf
(20 mol%), m-NO2C6H4COOH (40 mol%), Ru(bpy)3Cl2·6H2O
(3 mol%), Co(dmgH2)2Cl2 (8 mol%) were added to 1.0 mL solvent, then
deaerated and irradiated for 24 h by 0.5 W blue LEDs. [b] Determined by
1H NMR analysis using 1, 3, 5-trimethoxybenzene as an internal
standard. [c] The diastereomeric ratio, syn/anti, was determined by
1H NMR analysis. [d] Determined by HPLC analysis. [e] Yield of isolated
product. [f] 17% yield of H2. [g] 40 mol% nitrobenzene. [h] 95% yield of
aniline was detected by GC. [i] No Co(dmgH)2Cl2 and m-NO2C6H4COOH.
Ad=adamantly, bpy=2,2’-bipyridine, ppy=2-phenylpyridine, PC=pho-
tocatalyst, n.r.=no reaction, Tf=trifluoromethanesulfonyl.
previously observed in similar catalysis,[5] but also a hydrogen
acceptor and underwent in situ hydrogenation.[9e] This
hypothesis was proved when m-NO2C6H4COOH was
replaced by nitrobenzene and benzoic acid, and a 95%
yield of aniline was obtained with a slight reduction in the d.r.
and ee values (entry 16). When the reaction took place in air,
1a was competitively oxidized to the amide, 2-phenyl-3,4-
dihydroisoquinolin-1-one, and the yield decreased
dramatically (entry 17). When Co(dmgH)2Cl2 and m-
NO2C6H4COOH were further removed, 1a was almost
completely oxidized to 2-phenyl-3,4-dihydroisoquinolin-1-
one with 19% yield (entry 18).[10] Control experiments also
revealed that photocatalyst, cobalt catalyst, and visible light
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Scheme 4. Scope with respect to substituted ketones (d.r.: ratio of the
shown stereoisomer with all the other isomers). TEMPO=2,2,6,6-
tetramethylpiperidine-1-oxyl.
studies were carried out (see Figures S3–S9). No quenching of
2+
*Ru(bpy)3 luminescence was observed in the presence of
either aminocatalyst 4a/TfOH, 1a, or m-NO2C6H4COOH
alone. Instead, we observed a strong quenching by Co-
(dmgH)2Cl2 (Stern–Volmer constant of 1.1 ꢀ 105 mÀ1) and
a weak quenching effect by 1a/m-NO2C6H4COOH together
(Stern–Volmer constant is 3.1 ꢀ 102 mÀ1). These results
strongly suggest that the reaction is initialized by oxidative
quenching with a CoIII complex, instead of reductive quench-
ing with 1a as previously reported.[2e,4a,12] Electrochemical
Scheme 3. Scope with respect to ketones. [a] Eosin Y instead of
Ru(bpy)3Cl2·6H2O served as the photocatalyst. [b] Reaction at À58C.
[c] Reaction at 58C.
analysis showed that only Ru(bpy)3 (E1/2III/II = 1.29 V[13] vs.
3+
was determined by single-crystal X-ray diffraction and others
can be assigned accordingly (see Table S4).[17] 3-Methylcyclo-
hexanone and 4-ketalized cyclohexa-1,4-dione also worked
well in the reaction with good d.r. and ee values (3cg–h).
To probe the utility of our method in preparative syn-
thesis, a scale-up reaction of 1a with 2a was performed by
utilizing an organic dye photosensitizer in place of Ru-
(bpy)3Cl2·6H2O and decreasing the load of primary amine
catalyst (10 mol%) and cobalt catalyst (5 mol%). Under
these reaction conditions, conversion was complete within
48 hours with 72% yield, 7:1 d.r. and 96% ee
(Scheme 5a).
SCE), not *Ru(bpy)32+ (E1/2*II/I = 0.77 V vs. SCE),[13] is able to
oxidize 1a (0.88 V vs. SCE; see Figure S14), thus adding
further support to an oxidation quenching process. The weak
quenching efficiency with 1a/m-NO2C6H4COOH is also
consistent with the observed low reactivity in the absence of
the cobalt catalyst (Table 1, entry 19). In this context, an
electron-donor–acceptor (EDA) complex between 1a and
m-NO2C6H4COOH can be invoked to account for the weak
quenching effect in their co-existence.[10b,12a,c] This process
should be minor when CoIII complex is present.[14]
Experimentally, both butylated hydroxytoluene
(BHT) and TEMPO, the typical radical inhibitors,
slightly inhibited the reaction (Scheme 5b), and
suggested the key bond-formation step was not
radical in nature and the electron transfer was quite
facile and fast. Indeed, we could identify and track
the fast formation of the iminium cation intermediate
6 during the initial stage of reaction (see Schemes S3
and S4).[4l,11,12] The reaction could also be conducted
in a two-stage light/dark manner with similar out-
come (Scheme 5c). Those results indicated the sub-
À
sequent C C bond formation between the enamine
intermediate 7 and 6 might be the rate-determining
step in the whole reaction process.
To further shed light on the mechanism of amine
oxidation, flash photolysis and emission quenching
Scheme 5. The scale-up reaction and mechanistic insights.
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On the basis of the above observations, a plausible
Conflict of interest
catalytic cycle is proposed in Scheme 6. Upon visible-light
irradiation, the excited *[Ru(bpy)3]2+ is oxidized to
[Ru(bpy)3]3+ by [CoIII]. Single-electron oxidation of the
tertiary amine followed by hydrogen atom abstraction
(HAT) or e/H+ transformation results in the formation of
the iminium cation 6. The electron and proton are then
The authors declare no conflict of interest.
Keywords: amines · cross-coupling · hydrogen ·
photochemistry · reaction mechanisms
captured by [CoII] to form [CoI] and [CoIII H], which
À
hydrogenates m-NO2C6H4COOH to complete the cycle.
Meanwhile, interaction between the primary amine and
ketone generated enamine intermediate 7, which was
proven by a previous investigation.[5,15] Then 7 intercepts 6
to form the imine intermediate 9 through transition-state 8.[16]
Finally, hydrolysis of 9 provides the desired product and
allows the primary amine to re-enter the catalytic cycle.
[1] For selected reviews on direct dehydrogenative coupling, see:
a) T. Punniyamurthy, S. Velusamy, J. Iqbal, Chem. Rev. 2005, 105,
2329 – 2364; b) C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111,
1215 – 1292; c) S. A. Girard, T. Knauber, C.-J. Li, Angew. Chem.
Int. Ed. 2014, 53, 74 – 100; Angew. Chem. 2014, 126, 76 – 103;
d) C. Liu, J. Yuan, M. Gao, S. Tang, W. Li, R. Shi, A. Lei, Chem.
Rev. 2015, 115, 12138 – 12204.
[2] For leading examples on asymmetric dehydrogenative
coupling, see: a) Z. Li, C.-J. Li, Org. Lett. 2004, 6, 4997 –
4999; b) C. Dubs, Y. Hamashima, N. Sasamoto, T. M.
Seidel, S. Suzuki, D. Hashizume, M. Sodeoka, J. Org.
Chem. 2008, 73, 5859 – 5871; c) C. Guo, J. Song, S.-W.
Luo, L.-Z. Gong, Angew. Chem. Int. Ed. 2010, 49, 5558 –
5562; Angew. Chem. 2010, 122, 5690 – 5694; d) A. J.
Neel, J. P. Hehn, P. F. Tripet, F. D. Toste, J. Am. Chem.
Soc. 2013, 135, 14044 – 14047; e) G. Bergonzini, C. S.
Schindler, C.-J. Wallentin, E. N. Jacobsen, C. R. J.
Stephenson, Chem. Sci. 2014, 5, 112 – 116; f) S. Sun, C.
Li, P. E. Floreancig, H. Lou, L. Liu, Org. Lett. 2015, 17,
1684 – 1687; g) X.-H. Wei, G.-W. Wang, S.-D. Yang,
Chem. Commun. 2015, 51, 832 – 835.
[3] For selected examples on achiral CDC coupling of
tertiary amines to ketones, see: a) J. Xie, H. Li, J. Zhou,
Y. Cheng, C. Zhu, Angew. Chem. Int. Ed. 2012, 51,
1252 – 1255; Angew. Chem. 2012, 124, 1278 – 1281; b) H.
Ueda, K. Yoshida, H. Tokuyama, Org. Lett. 2014, 16,
4194 – 4197; c) C. Huo, M. Wu, X. Jia, H. Xie, Y. Yuan, J.
Tang, J. Org. Chem. 2014, 79, 9860 – 9864; d) Z. Xie, L.
Liu, W. Chen, H. Zheng, Q. Xu, H. Yuan, H. Lou,
Angew. Chem. Int. Ed. 2014, 53, 3904 – 3908; Angew.
Chem. 2014, 126, 3985 – 3989; e) X. Marset, J. M. Pꢁrez, D. J.
Ramꢂn, Green Chem. 2016, 18, 826 – 833.
Scheme 6. Plausible mechanism.
In summary, we have developed a visible-light-promoted
asymmetric CDC-type coupling of tertiary amines to ketones
enabled by a chiral primary amine catalyst, photocatalyst, and
cobalt catalyst. The salient features of this synergistic multiple
catalytic process involve the coupled tertiary amine oxidation
and nitro-compound reduction by Ru/Co-mediated e/H
shuttle as well as the realization of unprecedented syn-
[4] For leading examples on asymmetric a-coupling of carbonyls,
see: a) M. Rueping, C. Vila, R. M. Koenigs, K. Poscharny, D. C.
Fabry, Chem. Commun. 2011, 47, 2360 – 2362; b) G. Zhang, Y.
Ma, S. Wang, Y. Zhang, R. Wang, J. Am. Chem. Soc. 2012, 134,
12334 – 12337; c) G. Wei, C. Zhang, F. Bures, X. Ye, C.-H. Tan, Z.
Jiang, ACS Catal. 2016, 6, 3708 – 3712; d) G. Zhang, Y. Zhang, R.
Wang, Angew. Chem. Int. Ed. 2011, 50, 10429 – 10432; Angew.
Chem. 2011, 123, 10613 – 10616; e) B. Zhang, S.-K. Xiang, L.-H.
Zhang, Y. Cui, N. Jiao, Org. Lett. 2011, 13, 5212 – 5215; f) J.
Zhang, B. Tiwari, C. Xing, X. Chen, Y. R. Chi, Angew. Chem. Int.
Ed. 2012, 51, 3649 – 3652; Angew. Chem. 2012, 124, 3709 – 3712;
g) G. Zhang, Y. Ma, S. Wang, W. Kong, R. Wang, Chem. Sci.
2013, 4, 2645 – 2651; h) W. Cao, X. Liu, R. Peng, P. He, L. Lin, X.
Feng, Chem. Commun. 2013, 49, 3470 – 3472; i) Z. Meng, S. Sun,
H. Yuan, H. Lou, L. Liu, Angew. Chem. Int. Ed. 2014, 53, 543 –
547; Angew. Chem. 2014, 126, 553 – 557; j) Y. Tan, W. Yuan, L.
Gong, E. Meggers, Angew. Chem. Int. Ed. 2015, 54, 13045 –
13048; Angew. Chem. 2015, 127, 13237 – 13240; k) C. Wang, J.
Qin, X. Shen, R. Riedel, K. Harms, E. Meggers, Angew. Chem.
Int. Ed. 2016, 55, 685 – 688; Angew. Chem. 2016, 128, 695 – 698;
l) A. Sud, D. Sureshkumar, M. Klussmann, Chem. Commun.
2009, 3169 – 3171; m) Y. Pan, C. W. Kee, L. Chen, C.-H. Tan,
Green Chem. 2011, 13, 2682 – 2685; n) D. A. DiRocco, T. Rovis,
J. Am. Chem. Soc. 2012, 134, 8094 – 8097; o) Z.-J. Feng, J. Xuan,
À
selective C C bond formation with high diastereo- and
enantioselectivity. The consecutive low-barrier electron-
transfer process, made possible by coupled Ru/Co catalysis,
overcomes the high barriers of direct oxidation of substrates
and avoids the undesired byproducts associated with typical
oxidation processes. The current strategy would find more
application in elusive asymmetric oxidative transformations.
Acknowledgements
We thank the Natural Science Foundation of China
(21390400, 21572232, 21672217 and 21521002) for financial
support. S.L. is supported by the National Program of Top-
notch Young Professionals and CAS One-hundred Talents
Program.
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X.-D. Xia, W. Ding, W. Guo, J.-R. Chen, Y.-Q. Zou, L.-Q. Lu, W.-
[10] a) P. Kohls, D. Jadhav, G. Pandey, O. Reiser, Org. Lett. 2012, 14,
J. Xiao, Org. Biomol. Chem. 2014, 12, 2037 – 2040.
[5] a) S. Luo, H. Xu, J. Li, L. Zhang, J.-P. Cheng, J. Am. Chem. Soc.
2007, 129, 3074 – 3075; b) C. Xu, L. Zhang, S. Luo, Angew. Chem.
Int. Ed. 2014, 53, 4149 – 4153; Angew. Chem. 2014, 126, 4233 –
4237; c) L. Zhang, N. Fu, S. Luo, Acc. Chem. Res. 2015, 48, 986 –
997.
[6] For selected reviews on enantioselective catalysis of photo-
chemical reactions, see: a) R. Brimioulle, D. Lenhart, M. M.
Maturi, T. Bach, Angew. Chem. Int. Ed. 2015, 54, 3872 – 3890;
Angew. Chem. 2015, 127, 3944 – 3963; b) E. Meggers, Chem.
Commun. 2015, 51, 3290 – 3301.
[7] For selected reviews on dual catalysis, see: a) A. E. Allen,
D. W. C. Macmillan, Chem. Sci. 2012, 3, 633 – 658; b) M. N.
Hopkinson, B. Sahoo, J.-L. Li, F. Glorius, Chem. Eur. J. 2014, 20,
3874 – 3886; c) J. C. Tellis, C. B. Kelly, D. N. Primer, M. Jouf-
froyb, N. R. Patel, G. A. Molander, Acc. Chem. Res. 2016, 49,
1429 – 1439; d) K. L. Skubi, T. R. Blum, T. P. Yoon, Chem. Rev.
2016, 116, 10035 – 10074.
[8] For leading examples by merging photocatalysis and amino-
catalysis, see: a) A. Cꢂrdova, H. Sundꢁn, M. Engqvist, I.
Ibrahem, J. Casas, J. Am. Chem. Soc. 2004, 126, 8914 – 8915;
b) D. A. Nicewicz, D. W. C. MacMillan, Science 2008, 322, 77 –
80; c) H.-W. Shih, M. N. V. Wal, R. L. Grange, D. W. C. Mac-
Millan, J. Am. Chem. Soc. 2010, 132, 13600 – 13603; d) M. T.
Pirnot, D. A. Rankic, D. B. C. Martin, D. W. C. MacMillan,
Science 2013, 339, 1593 – 1596; e) M. Cherevatskaya, M. Neu-
mann, S. Fꢃldner, C. Harlander, S. Kꢃmmel, S. Dankesreiter, A.
Pfitzner, K. Zeitler, B. Kçnig, Angew. Chem. Int. Ed. 2012, 51,
4062 – 4066; Angew. Chem. 2012, 124, 4138 – 4142; f) Y. Zhu, L.
Zhang, S. Luo, J. Am. Chem. Soc. 2014, 136, 14642 – 14645;
g) J. J. Murphy, D. Bastida, S. Paria, M. Fagnoni, P. Melchiorre,
Nature 2016, 532, 218 – 222.
672 – 675; b) X. Liu, X. Ye, F. Bures, H. Liu, Z. Jiang, Angew.
Chem. Int. Ed. 2015, 54, 11443 – 11447; Angew. Chem. 2015, 127,
11605 – 11609.
[11] a) X.-Z. Shu, Y.-F. Yang, X.-F. Xia, K.-G. Ji, X.-Y. Liu, Y.-M.
Liang, Org. Biomol. Chem. 2010, 8, 4077 – 4079; b) M. Rueping,
J. Zoller, D. C. Fabry, K. Poscharny, R. M. Koenigs, T. Weirich, J.
Mayer, Chem. Eur. J. 2012, 18, 3478 – 3481; c) F. Rusch, L.-N.
Unkel, D. Alpers, F. Hoffmann, M. Brasholz, Chem. Eur. J. 2015,
21, 8336 – 8340; d) J. F. Franz, W. B. Krausab, K. Zeitler, Chem.
Commun. 2015, 51, 8280 – 8283.
[12] a) H. Bartling, A. Eisenhofer, B. Kçnig, R. M. Gschwind, J. Am.
Chem. Soc. 2016, 138, 11860 – 11871; b) J. Xie, Q. Xue, H. Jin, H.
Li, Y. Cheng, C. Zhu, Chem. Sci. 2013, 4, 1281 – 1286; c) A. G.
Condie, J. C. Gonzꢄlez-Gꢂmez, C. R. J. Stephenson, J. Am.
Chem. Soc. 2010, 132, 1464 – 1465.
[13] C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013,
113, 5322 – 5363.
[14] We did not detect obvious absorption at l > 350 nm, thus
indicating that such an EDA complex may be weak or transient
under the current reaction conditions. In addition, the photo-
catalytic mechanism between 1a/m-NO2C6H4COOH and the
RuII complex remains obscure. Either PET or energy transfer
may work in this context. Comparing with Rovisꢅ system
(Ref. [3n]), the low irradiation power in our case (0.5 W vs.
15 W) may be the reason why additional photocatalyst was
required to facilitate the photocatalytic cycle with EDA-type
complex.
[15] a) L. Zhang, C. Xu, X. Mi, S. Z. Luo, Chem. Asian J. 2014, 9,
3565; b) A. Simon, A. J. Yeh, Y.-H. Lam, K. N. Houk, J. Org.
Chem. 2016, 81, 12408 – 12415.
[16] In the transition-state 8, we speculate that the protonated
tertiary amine moiety guides the Re–Si coupling of iminium
cation and the secondary enamine by mixed steric and electro-
static repulsion effects (see Figure S15 for a full list of TSs). A
detailed mechanistic investigation of this reaction is under way
in our laboratory.
[9] a) J.-J. Zhong, Q.-Y. Meng, B. Liu, X.-B. Li, X.-W. Gao, T. Lei,
C.-J. Wu, Z.-J. Li, C.-H. Tung, L.-Z. Wu, Org. Lett. 2014, 16,
1988 – 1991; b) X.-W. Gao, Q.-Y. Meng, J.-X. Li, J.-J. Zhong, T.
Lei, X.-B. Li, C.-H. Tung, L.-Z. Wu, ACS Catal. 2015, 5, 2391 –
2396; c) G. Zhang, C. Liu, H. Yi, Q. Meng, C. Bian, H. Chen, J.-
X. Jian, L.-Z. Wu, A. Lei, J. Am. Chem. Soc. 2015, 137, 9273 –
9280; d) Y.-W. Zheng, B. Chen, P. Ye, K. Feng, W. Wang, Q.-Y.
Meng, L.-Z. Wu, C.-H. Tung, J. Am. Chem. Soc. 2016, 138,
10080 – 10083; e) J.-J. Zhong, C.-J. Wu, Q.-Y. Meng, X.-W. Gao,
T. Lei, C.-H. Tung, L.-Z. Wu, Adv. Synth. Catal. 2014, 356, 2846 –
2852.
[17] CCDC 1532741 (3ac) and 1532659 (3cd) contain the supple-
mentary crystallographic data for this paper. These data are
provided free of charge by The Cambridge Crystallographic
Data Centre.
Manuscript received: January 17, 2017
Final Article published: && &&, &&&&
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Cross-Coupling
Q. Yang, L. Zhang, C. Ye, S. Luo,*
L.-Z. Wu,* C.-H. Tung
&&&& — &&&&
Visible-Light-Promoted Asymmetric
Cross-Dehydrogenative Coupling of
Tertiary Amines to Ketones by Synergistic
Multiple Catalysis
Working together: Synergistic multiple
catalytic cycles enable an asymmetric
cross-dehydrogenative coupling between
tertiary amines and simple ketones with
high diastereo- and enantioselectivity
under visible-light irradiation. This pro-
cess is enabled by a simple chiral primary
amine catalyst through the coupling of
a catalytic enamine intermediate and an
iminium cation intermediate in situ gen-
erated from tetrahydroisoquinoline
derivatives by Ru/Co catalysis.
6
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!