Iridium-CNP complex catalyzed cross-coupling of primary alcohols and secondary alcohols by a borrowing hydrogen strategy

Article abstract of DOI:10.1039/c4ra06474g

A highly efficient C-C bond formation has been developed through the cross-coupling of primary and secondary alcohols. The corresponding functionalized ketones were obtained with an iridium-CNP complex as a catalyst through the borrowing hydrogen strategy. The present methodology provides an easy alternative method to aldol reaction derivatives. More importantly, the complexes were also effective catalysts for the alkylation of an aromatic amine with a tertiary alkyl amine. This journal is

Full text of DOI:10.1039/c4ra06474g

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Iridium–CNP complex catalyzed cross-coupling of
primary alcohols and secondary alcohols by a
borrowing hydrogen strategy†
Cite this: RSC Adv., 2014, 4, 42924
Received 1st July 2014
Accepted 29th August 2014
*
*
Dawei Wang, Keyan Zhao, Xin Yu, Hongyan Miao and Yuqiang Ding
DOI: 10.1039/c4ra06474g
www.rsc.org/advances
A highly efficient C–C bond formation has been developed through
the cross-coupling of primary and secondary alcohols. The corre-
sponding functionalized ketones were obtained with an iridium–CNP
complex as a catalyst through the borrowing hydrogen strategy. The
present methodology provides an easy alternative method to aldol
reaction derivatives. More importantly, the complexes were also
effective catalysts for the alkylation of an aromatic amine with a
tertiary alkyl amine.
Scheme 2 Benzothienyl skeleton phosphine ligand Ir(III) complexes.
The borrowing hydrogen reaction has attracted considerable
attention over the past ten years, emerging as a promising new
catalytic transformation that provides a useful alternative
method to the conventional alkylation of amines with a more
atom-efficient, greener process.1,2 The borrowing hydrogen
process usually involves the activation of alcohols through the
removal of hydrogen to form aldehydes or ketones, which react
with amines to form imines, followed by reduction using the
hydrogen generated in a dehydrogenation step to obtain an
N-alkylated amine product.3,4 Compared to the reactions of
alcohols with amines, the development of borrowing hydrogen
Table 1 Screening of optimized reaction conditions for benzyl alcohol
(3a) with 1-phenylethanol (4a)a
Entry
Catalyst
Base
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
1a
1b
2a
2b
2c
2d
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2a
2c
2d
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
none
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
DMSO
DMF
Toluene
MeCN
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
32
38
52
55
54
55
67
65
74
64
45
69
55
66
89
87
85
86
88
9
10
11
12
13
14
15
16
17
18
19
KOH
Et3N
Na2CO3
CsCO3
tBuOK
CsCO3
CsCO3
CsCO3
Scheme 1 C–C formation using the borrowing hydrogen strategy.
The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School
of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, Jiangsu
Province, China. E-mail: wangdw@jiangnan.edu.cn; yding@jiangnan.edu.cn
† Electronic supplementary information (ESI) available: Detailed experimental
procedures, 1H NMR, 13C NMR data for 5 and 7. See DOI: 10.1039/c4ra06474g
a
Reagents and conditions: benzyl alcohol (1.1 mmol), 1-phenylethanol
(1 mmol), cat [Ir] loading (2 mol%), base (1 mmol), solvent (2 mL), 110
ꢀC, 16 h, N2. b Isolated yield.
42924 | RSC Adv., 2014, 4, 42924–42929
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
Table 2 Iridium(III) complex 2b catalyzed reaction of primary and secondary alcoholsa
Entry
1
Primary alcohol
Secondary alcohol
Product
Yieldb (%)
5a, 89
2
3
5b, 97
5c, 81
4
5d, 85
5
6
7
5e, 82
5f, 78
5g, 74
8
5h, 69
9
5i, 73
5j, 81
5k, 79
10
11
12
13
5l, 82
5m, 78
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 42924–42929 | 42925

View Article Online
RSC Advances
Communication
Table 2 (Contd.)
Entry
14
Primary alcohol
Secondary alcohol
Product
Yieldb (%)
5n, 58
15
16
5o, 63
5p, 73
17c
18c
19c
5q, 46
5r, 31
5s, 62
20d
5t, 59
a
Reagents and conditions: primary alcohol (1.1 mmol), secondary alcohol (1 mmol), cat 3b (2 mol%), Cs2CO3 (1 mmol), toluene (2 mL), 110 ꢀC, 16 h,
N2. b Isolated yield. c Primary alcohol (10–15 mmol). d Primary alcohol (5 mmol).
reactions with respect to alcohols with alcohols is slower and functionalized ketones were obtained with iridium–CNP
more difficult, as it is burdened by the problems of low effi- complexes as catalysts through the borrowing hydrogen
ciency and high temperature.5 The cross-coupling reaction strategy.
involves the following process: (1) successive dehydrogenation
In order to evaluate the inuence of the various reported
of two molecules of alcohol to the corresponding carbonyl iridium catalysts, the reaction of benzyl alcohol (3a) with 1-
compounds; (2) aldol condensation of the foregoing to form an phenylethanol (4a) was chosen as the model substrate for the
unsaturated carbonyl compound (Scheme 1); and (3) reduction optimization of catalytic activity and selectivity (Table 1). First,
of the C–C double bond using the borrowed H2 from one we examined the activity of those iridium complexes, whereby
molecule of alcohol6 water and hydrogen are produced as the results showed that the yield of the product (5a) increased
byproducts, and the atom efficiency of this system is high.7
with benzothienyl skeleton phosphine ligand iridium(III)
We recently reported on the phosphorescent benzothienyl complexes in the following order: 2b > 2d > 2c > 2a > 1b > 1a. It
iridium(III) complexes8 with catalytic activity enhanced by should be noted that nearly all the catalysts with non-coordi-
phosphine ligand and non-coordinating anion (Scheme 2).9 nating anion gave excellent yields.
These complexes provide a very efficient alternative method for
The reaction conditions were further optimized through the
the alkylation of amines. Here, in this paper we report that the use of various solvents. The yield of product was signicantly
42926 | RSC Adv., 2014, 4, 42924–42929
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
lower in polar solvent, toluene was found to be the most suit-
able among the solvents tested. The blank test showed that
bases played an important role in the reaction, so a number of
bases were checked. The result of the comparison of alkaline
carbonates suggested that the alcohol-dehydrogenation and
aldol-condensation steps demand stronger basic sites. Cs2CO3
and tBuOK efficiently provided the C–C formation reaction, but
Cs2CO3 was relatively more effective. Under the optimized
conditions (benzyl alcohol (1.1 mmol), 1-phenylethanol (1
mmol), [Ir] loading (2 mol%), Cs2CO3 (1 mmol), toluene (2 mL),
110 ꢀC, 16 h, under nitrogen), phenethyl phenylketone (5a) was
formed at a yield of 89% with catalyst 2b, while 3a, 3c, 3d
afforded more than 85% yield of the desired product.
Scheme 3 The reaction pathway of alkylation of an aromatic amine
with a tertiary alkyl amine.
58% yield of the desired product. This, we believe, it is attrib-
utable to the triuoromethyl strong electron-withdrawal
(Table 2, entry 14).
Given the optimized reaction conditions, we investigated the
scope of the reaction with a series of secondary and primary
alcohols (Table 2). The reactions of 1-phenylethanol with
different types of aromatic alcohols occurred well, providing
moderate to excellent yields (Table 2, entries 1–8). Chlorinated
aromatic alcohol and electron-donating substituent were well
tolerated in the reactions, while pyridyl-, furyl-, thienyl-hetero-
cyclic alcohols could react under the optimal reaction condi-
tions with the overall yield in 69–85%. Next, pyridyl heterocyclic
alcohols with diverse phenylethanols were explored (Table 2,
entries 9–13 and 15–16). Generally, phenylethanols possessing
electron-donating groups gave the corresponding products in
higher yields as compared to electron-poor ones, while benzyl
alcohol with 1-[4-(triuoromethyl)phenyl]ethanol afforded only
We were pleased that aliphatic alcohols were effective
for this methodology. Of those, iso-octyl alcohol, 1-pentanol,
n-propanol and isobutanol are representative (Table 2, entries
17–20). The corresponding target products were all separated
smoothly, while the yields were signicantly lower than those of
aromatic alcohols.
In addition, we also explored the borrowing hydrogen reac-
tion of an aromatic amine with a tertiary alkyl amine10 To our
surprise, the substrate experiments showed that the reactions
carried on smoothly and the desired products were separated
with moderate to good yields (Table 3). When meta-substituted
aniline was tried in this reaction, the product was also obtained
with moderate yield (Table 3, entry 5). It should be noted that
substrate containing a pyridine group showed only 58% yield
(Table 3, entry 3).
Finally, a reaction pathway was proposed about this alkyl-
ation of an aromatic amine with a tertiary alkyl amine (Scheme
3). This transformation is a litter different from alkylation of
two molecules of alcohols, despite the intermediate iminium
ion is identical. Diethylamine is produced as a byproduct in this
transformation,10a,10c while there are water and H2 as byproducts
in alkylation of two molecules alcohols.
Table 3 The alkylation of an aromatic amine with a tertiary alkyl amine
by borrowing hydrogen strategya
Entry
1
Amine
Product
Yieldb (%)
Conclusions
In summary, highly efficient C–C bond formation was devel-
oped through the hydrogen autotransfer cross-coupling of
secondary and primary alcohols. The corresponding function-
alized ketones were obtained with iridium–CNP complex as a
catalyst through the borrowing hydrogen strategy, and the
substrate scope was wide. The present work is providing an easy
step forward for the synthesis of ketones. The borrowing
hydrogen reaction of an aromatic amine with a tertiary alkyl
amine also works well.
7a, 65
2
3
4
7b, 72
7c, 58
7d, 78
Acknowledgements
We gratefully acknowledge nancial support of this work by the
National Natural Science Foundation of China (nos 21401080,
21371080), the Natural Science Foundation of Jiangsu Province
of China (BK20130125), and MOE & SAFEA for the 111 Project
(B13025).
5
7e, 63
a
Conditions: 5 (1.0 mmol), triethylamine (20 mmol), 2b (2 mol%),
Cs2CO3 (1.1 mmol), xylene (2 mL), 150 ꢀC, 24 h, N2. b Isolated yield.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 42924–42929 | 42927

View Article Online
RSC Advances
Communication
M. K. Brinks, F. Rominger, P. Hofmann and M. Limbach,
ACS Catal., 2014, 4, 152; (g) J. Kamalraja, P. Murugasan
and P. T. Perumal, RSC Adv., 2014, 4, 19422; (h)
M. Koohshari, M. Dabiri and P. Salehi, RSC Adv., 2014, 4,
10669; (i) R. Mudududdla, R. Sharma, S. K. Guru,
M. Kushwaha, A. P. Gupta, S. S. Bharate, S. Aravinda,
R. Kant, S. Bhushan, R. A. Vishwakarma and S. B. Bharate,
RSC Adv., 2014, 4, 14081; (j) M. Sathishkumar and
K. I. Sathiyanarayanan, RSC Adv., 2014, 4, 8808.
5 (a) K.-I. Fujita, C. Asai, T. Yamaguchi, F. Hanasaka and
R. Yamaguchi, Org. Lett., 2005, 7, 4017; (b) M. Viciano,
M. Sanau and E. Peris, Organometallics, 2007, 26, 6050; (c)
A. Prades, M. Viciano, M. Sanau and E. Peris,
Organometallics, 2008, 27, 4254; (d) A. P. da Costa,
M. Viciano, M. Sanau, S. Merino, J. Tejeda, E. Peris and
References
1 For recent reviews, see: (a) M. H. S. A. Hamid, P. A. Slatford
and J. M. J. Williams, Adv. Synth. Catal., 2007, 349, 1555; (b)
´
´
S. Dıez-Gonzalez, N. Marion and S. P. Nolan, Chem. Rev.,
´
2009, 109, 3612; (c) G. Guillena, D. J. Ramon and M. Yus,
Chem. Rev., 2010, 110, 1611; (d) T. Suzuki, Chem. Rev.,
2011, 111, 1825; (e) M. Stratakis and H. Garcia, Chem. Rev.,
2012, 112, 4469; (f) S. E. Allen, R. R. Walvoord, R. Padilla-
Salinas and M. C. Kozlowski, Chem. Rev., 2013, 113, 6234.
2 (a) D. Hollmann, S. Bahn, A. Tillack and M. Beller, Chem.
Commun., 2008, 3199; (b) O. Saidi, A. J. Blacker,
M. M. Farah, S. P. Marsden and J. M. J. Williams, Angew.
Chem., Int. Ed., 2009, 48, 7375; (c) X. Tan, B. Li, S. Xu,
H. Song and B. Wang, Organometallics, 2013, 32, 3253; (d)
A. Quintard, T. Constantieux and J. Rodriguez, Angew.
Chem., Int. Ed., 2013, 52, 12883; (e) M. Zhang, H. Neumann
and M. Beller, Angew. Chem., Int. Ed., 2013, 52, 597; (f)
M. Zhang, X. Fang, H. Neumann and M. Beller, J. Am.
Chem. Soc., 2013, 135, 11384; (g) C. Sun, X. Zou and F. Li,
Chem.–Eur. J., 2013, 19, 14030; (h) C. Gunanathan and
D. Milstein, Science., 2013, 341, 249; (i) P. Qu, C. Sun, J. Ma
and F. Li, Adv. Synth. Catal., 2014, 356, 447; (j) F. Xie,
M. Chen, X. Wang, H. Jiang and M. Zhang, Org. Biomol.
Chem., 2014, 12, 2761; (k) X. Ye, P. N. Plessow,
M. K. Brinks, M. Schelwies, T. Schaub, F. Rominger,
R. Paciello, M. Limbach and P. Hofmann, J. Am. Chem.
Soc., 2014, 136, 5923; (l) Y. Zhang, C.-S. Lim, D. S. B. Sim,
H.-J. Pan and Y. Zhao, Angew. Chem., Int. Ed., 2014, 53, 1399.
3 For some selected recent examples, see: (a) A. Kumar,
S. Sharma and R. A. Maurya, Adv. Synth. Catal., 2010, 352,
B. Royo, Organometallics,
2008, 27, 1305;
(e)
P. Satyanarayana, G. M. Reddy, H. Maheswaran and
M. L. Kantama, Adv. Synth. Catal., 2013, 355, 1859; (f)
D. Gelman and R. Romm, Top. Organomet. Chem., 2013, 40,
289; (g) S. Musa, R. Romm, C. Azerraf, S. Kozuch and
D. Gelman, Dalton Trans., 2011, 40, 8760; (h) K. Oded,
S. Musa, D. Gelman and J. Blum, Catal. Commun., 2012, 20,
68; (i) S. Musa, I. Shaposhnikov, S. Cohen and D. Gelman,
Angew. Chem., Int. Ed., 2011, 50, 3533; (j) S. Musa,
S. Fronton, L. Vaccaro and D. Gelman, Organometallics,
2013, 32, 3069; (k) G. R. A. Adair and J. M. J. Williams,
Tetrahedron Lett., 2005, 46, 8233; (l) L. J. Allen and
R. H. Crabtree, Green Chem., 2010, 12, 1362; (m) Q. Xu,
J. Chen and Q. Liu, Adv. Synth. Catal., 2013, 355, 697; (n)
S. Musa, L. Ackermann and D. Gelman, Adv. Synth. Catal.,
2013, 355, 3077.
´
´
6 (a) L. Guo, Y. Liu, W. Yao, X. Leng and Z. Huang, Org. Lett.,
2013, 15, 1144; (b) K. Park, Angew. Chem., Int. Ed., 2005, 44,
6913; (c) Y. M. A. Yamada and Y. Uozumi, Org. Lett., 2006,
8, 1375; (d) K.-I. Shimizu, R. Sato and A. Satsuma, Angew.
Chem., Int. Ed., 2009, 48, 3982; (e) X. Cui, Y. Zhang, F. Shi
and Y. Deng, Chem.–Eur. J., 2011, 17, 1021; (f)
S. Gowrisankar, H. Neumann and M. Beller, Angew. Chem.,
Int. Ed., 2011, 50, 5139; (g) T. Miura, O. Kose, F. Li, S. Kai
and S. Saito, Chem.–Eur. J., 2011, 17, 11146; (h) L. Guo,
Y. Liu, W. Yao, X. Leng and Z. Huang, Org. Lett., 2013, 15,
1144; (i) S. Ogawa and Y. Obora, Chem. Commun., 2014, 50,
2491; (j) L. K. M. Chan, D. L. Poole, D. Shen, M. P. Healy
and T. J. Donohoe, Angew. Chem., Int. Ed., 2014, 53, 761; (k)
F.-X. Yan, M. Zhang, X.-T. Wang, F. Xie, M.-M. Chen and
H. Jiang, Tetrahedron, 2014, 70, 1193; (l) Y. Obora,
S. Ogawa and N. Yamamoto, J. Org. Chem., 2012, 77, 9429;
(m) I. S. Makarov and R. Madsen, J. Org. Chem., 2013, 78,
6593; (n) C. Xu, Y. Goh and S. A. Pullarkat, Organometallics,
2011, 30, 6499; (o) X. Gong, H. Zhang and X. Li,
Tetrahedron Lett., 2011, 52, 5596; (p) X. Chang,
L. W. Chuan, Y. Li and S. A. Pullarkat, Tetrahedron Lett.,
2012, 53, 1450; (q) S. Liao, K. Yu, Q. Li, H. Tian, Z. Zhang,
X. Yu and Q. Xu, Org. Biomol. Chem., 2012, 10, 2973; (r)
D. Wang, R. Cai, S. Sharma, J. Jirak, S. K. Thummanapelli,
N. G. Akhmedov, H. Zhang, X. Liu, J. L. Petersen and
X. Shi, J. Am. Chem. Soc., 2012, 134, 9012.
2227; (b) A. Martınez-Asencio, D. J. Ramon and M. Yus,
´
Tetrahedron Lett., 2010, 51, 325; (c) R. Cano, D. J. Ramon
and M. Yus, J. Org. Chem., 2011, 76, 5547; (d) R. Ghosh and
A. Sarkar, J. Org. Chem., 2011, 76, 8508; (e) W. He, L. Wang,
C. Sun, K. Wu, S. He, J. Chen, P. Wu and Z. Yu, Chem.–Eur.
J., 2011, 17, 13308; (f) S. Agrawal, M. Lenormand and
B. Martın-Matute, Org. Lett., 2012, 14, 1456; (g)
A. Bartoszewicz, R. Marcos, S. Sahoo, A. K. Inge, X. Zou
´
´
and B. Martın-Matute, Chem.–Eur. J., 2012, 18, 14510; (h)
H.-Y. Kuo, Y.-H. Liu, S.-M. Peng and S.-T. Liu,
Organometallics, 2012, 31, 7248; (i) F. Xie, M. Chen,
X. Wang, H. Jiang and M. Zhang, Org. Biomol. Chem., 2014,
12, 2761; (j) X. Xu, M. Zhang, H. Jiang, J. Zheng and Y. Li,
´
Org. Lett., 2014, 16, 3540; (k) C. Segarra, E. Mas-Marza,
J. Mata and E. Peris, Adv. Synth. Catal., 2011, 353, 2078.
4 (a) D. Wang, X.-Q. Guo, C.-X. Wang, Y.-N. Wang, R. Zhong,
X.-H. Zhu, L.-H. Cai, Z.-W. Gao and X.-F. Hou, Adv. Synth.
Catal., 2013, 355, 1117; (b) D. Weickmann, W. Frey and
B. Plietker, Chem.–Eur. J., 2013, 19, 2741; (c) A. Wetzel,
¨
S. Wockel, M. Schelwies, M. K. Brinks, F. Rominger,
P. Hofmann and M. Limbach, Org. Lett., 2013, 15, 266; (d)
F. Santoro, R. Psaro, N. Ravasio and F. Zaccheria, RSC Adv.,
2014, 4, 2596; (e) M. Ousmane, G. Perrussel, Z. Yan,
J. M. Clacens, F. De Campo and M. Pera-Titus, J. Catal.,
2014, 309, 439; (f) S. Wockel, P. Plessow, M. Schelwies,
42928 | RSC Adv., 2014, 4, 42924–42929
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
7 (a) M. H. S. A. Hamid, C. L. Allen, G. W. Lamb, A. C. Maxwell,
H. C. Maytum, A. J. A. Watson and J. M. J. Williams, J. Am.
Chem. Soc., 2009, 131, 1766; (b) K. Yamaguchi, J. He,
T. Oishi and N. Mizuno, Chem.–Eur. J., 2010, 16, 7199; (c)
Q. Song, S. Zhang, Q. Wang and Y. Ding, Organometallics,
2013, 32, 4130.
9 D. Wang, K. Zhao, H. Wang, X. Yu and Y. Ding, RSC Adv.,
under review.
H. Liu, G.-K. Chuah and S. Jaenicke, J. Catal., 2012, 292, 10 (a) O. Saidi, A. J. Blacker, M. M. Farah, S. P. Marsden and
130; (d) J. F. Soule, H. Miyamura and S. Kobayashi, Chem.
Commun., 2013, 49, 355; (e) W. Baumann, A. Spannenberg,
J. Pfeffer, T. Haas, A. Kockritz, A. Martin and J. Deutsch,
Chem.–Eur. J., 2013, 19, 17702; (f) J. A. Mata, F. E. Hahn
and E. Peris, Chem. Sci., 2014, 5, 1723; (g) A. I. Carrillo,
J. M. Williams, Angew. Chem., Int. Ed., 2009, 48, 7375–7378;
(b) K.-I. Shimizu, K. Shimura, K. Ohshima, M. Tamura and
A. Satsuma, Green Chem., 2011, 13, 3096–3100; (c)
K.-I. Shimizu, K. Ohshima, Y. Tai, M. Tamura and
A. Satsuma, Catal. Sci. Technol., 2012, 2, 730–738; (d)
X. Tan, B. Li, S. Xu, H. Songand and B. Wang,
Organometallics, 2013, 32, 3253–3261.
´
L. C. Schmidt, M. L. Marınab and J. C. Scaiano, Catal. Sci.
Technol., 2014, 4, 435.
8 (a) W. Yang, H. Fu, Q. Song, M. Zhang and Y. Ding,
Organometallics, 2011, 30, 77; (b) W. Yang, D. Wang,
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 42924–42929 | 42929