Copper(i)-catalysed transfer hydrogenations with ammonia borane

Article abstract of DOI:10.1039/c6cc09067b

Highly Z-selective alkyne transfer semihydrogenations and conjugate transfer hydrogenations of enoates can be effected by employing a readily available and air-stable copper(i)/N-heterocyclic carbene (NHC) complex, [IPrCuOH]. As an easy to handle and potentially recyclable H₂ source, ammonia borane (H₃NBH₃) is used.

Full text of DOI:10.1039/c6cc09067b

ChemComm
View Article Online
View Journal
COMMUNICATION
Copper(I)-catalysed transfer hydrogenations with
ammonia borane†
Cite this:DOI: 10.1039/c6cc09067b
Eva Korytiakova, Niklas O. Thiel, Felix Pape and Johannes F. Teichert*
´
Received 13th November 2016,
Accepted 12th December 2016
DOI: 10.1039/c6cc09067b
www.rsc.org/chemcomm
Highly Z-selective alkyne transfer semihydrogenations and conjugate
transfer hydrogenations of enoates can be effected by employing
a readily available and air-stable copper(I)/N-heterocyclic carbene
(NHC) complex, [IPrCuOH]. As an easy to handle and potentially
recyclable H2 source, ammonia borane (H3NBH3) is used.
Ammonia borane (H3NBH3), an easy to prepare and manipulate
solid, has attracted interest as a potential dihydrogen (H2) storage
material.1–6 Based on the fact that ammonia borane dehydrogena-
tion products (e.g., borazines and polyiminoboranes) can poten-
tially be recycled,7 and its exceptionally high H2 content, many
studies have been directed toward controlled catalytic release of
H2 (dehydrocoupling) from ammonia borane.1–6,8 Notably, to a
much lesser extent has H3NBH3 been employed as a reagent for
synthesis, for example in the reduction of functional groups or
transfer hydrogenations.9–11
Scheme 1 Hydride and dihydrogen sources employed for copper(I)
hydride catalysis.
Copper(I) hydride complexes have emerged as powerful catalysts for high pressure equipment. Given the synthetic utility of copper
for a wide variety of reductive transformations, generally relying on hydride complexes, we decided to investigate ammonia borane as
silanes12–15 or, to a much lesser extent, on tin hydrides16 or a reagent for copper-catalysed transfer hydrogenations.
dihydrogen17,18 (Scheme 1). These terminal reducing agents differ
We decided to optimise the copper(I)-catalysed transfer
conceptually: Si- and Sn-based compounds will deliver a hydride hydrogenation with H3NBH3 employing alkyne transfer semi-
equivalent and the reaction products remain silylated or hydrogenation of pentynol-derived alkyne 1 as a test reaction
stannylated until hydrolysis or protonation. On the other hand, (Table 1).23 Due to the reported reactivity with H2,18–20 we chose
reactions with H2 can directly deliver the hydride and proton well-defined copper(I)/NHC complexes bearing a copper–oxygen
equivalent, circumventing the need for an additional proton bond as the starting point for our studies. With a copper(I) tert-
source and reducing the waste generated in these processes. As butanolate complex, generated in situ from [IMesCuCl] and
an example, copper(I)-catalysed alkyne semihydrogenations have NaOtBu, we observed no turnover to the corresponding alkene
recently demonstrated the potential replacement of silanes with Z-2 at room temperature, but full conversion at 50 1C (Table 1,
H2.18–20 However, most of these procedures require elevated H2 entries 1 and 2). A similar trend was observed with a copper(I)
pressure and/or have a limited substrate scope.
hydroxide/NHC complex, [IPrCuOH],18b,24,25 which also under-
On the other hand, homogeneous transfer hydrogenations went full conversion to Z-2 at 50 1C (Table 1, entries 3–5).
with copper catalysts are scarce,21,22 but circumvent the need Increasing the temperature further to 60 1C led to diminished
conversion of 60% (Table 1, entry 6). The use of [IPrCuOH] is
¨
¨
Institut fur Chemie, Technische Universitat Berlin, Strasse des 17. Juni 115,
10623 Berlin, Germany. E-mail: johannes.teichert@chem.tu-berlin.de;
Fax: +49 30 314 28829; Tel: +49 30 314 22791
particularly attractive, as it does not require the generally
common in situ preactivation (to give activated copper(I) alkoxide
complexes) and is air-stable for months. It should be noted that in
all cases excellent Z-selectivity and negligible overreduction to the
corresponding alkane 3 were maintained. This is synthetically
† Electronic supplementary information (ESI) available: Preparation and char-
acterisation data as well as 1H and 13C NMR spectra of all compounds. See DOI:
10.1039/c6cc09067b
This journal is ©The Royal Society of Chemistry 2016
Chem. Commun.

View Article Online
Communication
ChemComm
Table 1 Optimisation of Cu-catalysed transfer semihydrogenation of alkynes
Entry
Conditions
Conv.a [%]
Z-2/E-2/3a
1
2
3
4
5
6
7
8
[IMesCuCl], 7.5 mol% NaOtBu, 3 equiv. of H3NBH3, THF, rt, 16 h
[IMesCuCl], 7.5 mol% NaOtBu, 3 equiv. of H3NBH3, THF, 50 1C, 16 h
[IPrCuOH], 3 equiv. of H3NBH3, THF, rt, 16 h
As entry 3, 40 1C
As entry 3, 50 1C
As entry 3, 60 1C
As entry 5, in C6H6
As entry 5, in CH2Cl2
[IPrCuOH], 3 equiv. of H3NBH3, THF, 50 1C, 4 h
[IPrCuOH], 2 equiv. of H3NBH3, THF, 50 1C, 4 h
[IPrCuOH], 20 mol% H3NBH3, 1 bar H2, THF, 50 1C, 16 h
—
499
9
—
499 : 0 : 0
499 : 0 : 0
499 : 0 : 0
499 : 0 : 0
499 : 0 : 0
499 : 0 : 0
n.d.
499 : 0 : 0
499 : 0 : 0
499 : 0 : 0
68
499
60
18
6
9b
10b
11
499c
88
20
a
b
c
Determined by 1H NMR and GC analysis. Slow addition of H3NBH3 in THF solution over 3 h. Isolated yield: 96%.
appealing, as alkyne semihydrogenations are commonly carried semihydrogenation. A variety of phenylacetylene derivatives with
out with heterogeneous palladium catalysts which generally suffer both electron-donating and electron-withdrawing functional groups
from these particular limitations.26 Furthermore, another report 4a–4g could successfully be transformed into alkenes 5a–5g with
of alkyne transfer semihydrogenation with copper catalysts does good yields and consistently high Z-selectivity (Table 2, entries 1–7).
not give turnover with internal alkynes,21c which underscores the Of note is the low conversion achieved with 3-anisole derivative 4d
orthogonal reactivity of the present catalyst.27
(30%, Table 2, entry 4); we suspect substrate coordination
The use of THF as a solvent proved to be optimal, as the reactions detrimental to the catalyst, which is absent with the other two
in benzene and dichloromethane under otherwise similar reaction regioisomers 4c and 4e (Table 2, entries 3 and 5). With strongly
conditions gave lower conversion of 1 (Table 1, entries 7 and 8). At electron-withdrawing substituents (as in 5h–5j, Table 2, entries 8–10),
the onset of the described reactions in THF, gas evolution (most we observed partial overreduction to the corresponding alkanes,
likely H2) was observed, accompanied by a relatively slow reaction although the Z/E-ratios remained high. The same is true for
rate (499% conversion was reached after B12 h reaction time). This the acetophenone derivative 4k, where overreduction to the
hinted at the loss of H2 equivalents for the desired transfer semihy- benzyl alcohol 5k was detected (Table 2, entry 11).29 A variety
drogenation through concomitant dehydrocoupling. Consequently, of Z-stilbenes 5l–5o can be synthesised from the corresponding
when an H3NBH3 solution in THF was added slowly (3 h) to the tolane derivatives 4l–4o with good yields (Table 2, entries 12–15).
reaction mixture, a generally faster conversion and higher yield of Here, a similarly detrimental influence of the electron-withdrawing
Z-2 were observed (Table 1, entry 9, 96%). Nevertheless, a total of trifluoromethyl substituent in 5o was observed as 8% alkane was
three equivalents of H3NBH3 were required for 499% conversion detected (Table 2, entry 15). The alkyne transfer semihydrogenation
since slow addition of two equivalents of ammonia borane did not can also be applied to dialkylalkynes, as demonstrated by the
lead to complete consumption of 1 (Table 1, entry 10).28 Based formation of Z-alkenes 5p and 5q (Table 2, entries 16 and 17). For
on these results, we decided to probe whether a direct transfer of full consumption of the former, one more equivalent of H3NBH3 was
a hydride equivalent to copper or H2 activation after dehydro- added. Finally, protected allyl alcohols 5r and 5s can be obtained
coupling of ammonia borane was present. Therefore, we carried with high Z-selectivity from the corresponding propargylic silyl ethers
out the alkyne transfer semihydrogenation with a catalytic 4r and 4s (Table 2, entries 18 and 19). Generally, the obtained yields
amount of H3NBH3 under a H2 atmosphere. These reactions are good; in some cases we observed undesired hydroboration/
gave only 20% conversion of 1 (Table 1, entry 11); hence, we oxidation of the alkene products.23 We attribute the somewhat
conclude that a direct hydride transfer mechanism is present. diminished yields to this side reaction.
With the optimised reaction conditions in hand, we explored
Finally, we investigated the transfer semihydrogenation of alkyl
the substrate scope of the copper-catalysed alkyne transfer and aryl propiolates 6 (Scheme 2). In both cases the desired
Chem. Commun.
This journal is ©The Royal Society of Chemistry 2016

View Article Online
ChemComm
Communication
Table 2 Cu-catalysed transfer semihydrogenation of alkynes with ammonia
borane: substrate scope
Scheme 2 Transfer semihydrogenation of propiolates.
Entry
1
Product
Yield [%]
Z/E/alkanea
499 : 0 : 0
5a: R = 4-Me
Z-acrylates 7a and 7b were found, however, in the presence of
overreduced esters 8a and 8b. This indicated the viability of a
conjugate transfer hydrogenation of the initially formed acrylates 7.
We therefore decided to investigate the conjugate transfer hydro-
genation of a,b-unsaturated esters with ammonia borane next.
After initial optimisation we also found that conjugate transfer
hydrogenation of enoates 9 with ammonia borane was feasible
under similar reaction conditions (Table 3). Conjugate transfer
hydrogenation of disubstituted ethyl esters 9a–9i could be
realised with generally good isolated yields when the reaction
was carried out under previously optimised conditions (Table 3,
entries 1–9). Isolated yields for esters 10 generally are higher
than in the alkyne transfer semihydrogenation. This is possibly
due to the absence of a reactive double bond in the products,
which could lead to further reactions. Only thiophene deriva-
tive 10f was obtained in a somewhat lower yield (Table 3,
entry 6). Of note is the different reactivity of the catalyst toward
double bond isomers: while the E-enoate 9d underwent smooth
conversion to the desired saturated product 10d (Table 3, entry 4),
the reaction with Z-enoate 9e proceeded sluggishly (46% con-
version to 10e after 16 h) under otherwise similar conditions
(Table 3, entry 5). Higher substituted acrylates 10j–10l proved
to be more difficult to obtain, most probably due to steric
hindrance (Table 3, entries 10–12). However, by addition of
6 equivalents of H3NBH3, esters 10j–10l could be isolated in
good yields.30
63
2
3
4
5
6
7
8
9
5b: R = 4-tBu
5c: R = 4-OMe
5d: R = 3-OMe
5e: R = 2-OMe
5f: R = Br
5g: R = Cl
5h: R = CO2Me
5i: R = CN
50
69
30 conv.
71
80
63
65
51
71
499 : 0 : 0
95 : 5 : 0
499 : 0 : 0
499 : 0 : 0
499 : 0 : 0
499 : 0 : 0
80 : 0 : 20
89 : 4 : 7
10
5j: R = CF3
5k:
81 : 0 : 19
11
55
84 : 1 : 15
5l: R = H
12
57
499 : 0 : 0
13
14
15
5m: R = 4-OMe
5n: R = 4-Cl
5o: R = 4-CF3
5p:
66
77
50
499 : 0 : 0
499 : 0 : 0
92 : 0 : 8
Table 3 Cu-catalysed conjugate transfer hydrogenation: substrate scope
16b
74
499 : 0 : 0
499 : 0 : 0
499 : 0 : 0
5q:
5r:
Entry
Product
Yield [%]
17
80 conv.
1a
2a
3a
4
10a: R1 = Ph, R2 = H
82
83
83
87
46 conv.
66
88
82
89
10b: R1 = 2-naphthyl, R2 = H
10c: R1 = 4-OMe-C6H4, R2 = H
10d: R1 = 4-OBn-C6H4, R2 = H
10e: R1 = H, R2 = 4-OBn-C6H4
10f: R1 = 2-thiophenyl, R2 = H
10g: R1 = cyclohexyl, R2 = H
10h: R1 = 4-Br-C6H4, R2 = H
10i: R1 = 4-CF3-C6H4, R2 = H
10j: R1 = 2-naphthyl, R2 = Me
10k: R1 = Ph, R2 = Me
5b
6
18
74
7a
8
9
5s:
10c
11c
12c
93
76
10l: R1 = Ph, R2 = Ph
73d
19
63
499 : 0 : 0
a
These reactions reached 499% conversion with 2 equiv. of H3NBH3.
The methyl ester of 9e was employed. 6 equiv. of H3NBH3 was used.
Contains 14% of the starting material.
b
d
c
a
b
Determined by 1H NMR and GC analysis. 4 equiv. of H3NBH3 was used.
This journal is ©The Royal Society of Chemistry 2016
Chem. Commun.

View Article Online
Communication
ChemComm
N.-Y. Chen, X. Liu, Z. Shao, S.-P. Luo and Q. Liu, J. Am. Chem. Soc.,
2016, 138, 8588–8594.
12 A. J. Jordan, G. Lalic and J. P. Sadighi, Chem. Rev., 2016, 116, 8318–8372.
13 C. Deutsch, N. Krause and B. H. Lipshutz, Chem. Rev., 2008, 108,
2916–2927.
14 S. Rendler and M. Oestreich, Angew. Chem., Int. Ed., 2007, 46,
498–504.
15 B. H. Lipshutz, in Copper(I)-mediated 1,2- and 1,4-Reductions. Modern
Organocopper Chemistry, ed. N. Krause, Wiley-VCH, Weinheim, 2002,
pp. 167–187.
16 (a) B. H. Lipshutz, C. Ung and S. Sengupta, Synlett, 1989, 64–66; (b) L. T.
Leung, S. K. Leung and P. Chiu, Org. Lett., 2005, 7, 5249–5252.
17 (a) W. S. Mahoney and J. M. Stryker, J. Am. Chem. Soc., 1989, 111,
8818–8823; (b) H. Shimizu, D. Igarashi, W. Kuriyama, Y. Yusa,
N. Sayo and T. Saito, Org. Lett., 2007, 9, 1655–1657; (c) K. Junge,
B. Wendt, D. Addis, S. Zhou, S. Das, S. Fleischer and M. Beller,
Chem. – Eur. J., 2011, 17, 101–105.
18 (a) F. Pape, N. O. Thiel and J. F. Teichert, Chem. – Eur. J., 2015, 21,
15934–15938; (b) N. O. Thiel and J. F. Teichert, Org. Biomol. Chem.,
2016, 14, 10660–10666.
19 K. Semba, R. Kameyama and Y. Nakao, Synlett, 2015, 318–322.
20 T. Wakamatsu, K. Nagao, H. Ohmiya and M. Sawamura, Organo-
metallics, 2016, 35, 1354–1357.
21 For examples of homogeneous copper-catalysed transfer hydrogena-
tions, see: (a) J. W. Yang and B. List, Org. Lett., 2006, 8, 5653–5655;
(b) K. Saito, Y. Kajiwara and T. Akiyama, Angew. Chem., Int. Ed., 2013,
52, 13284–13288; (c) H. Cao, T. Chen, Y. Zhou, D. Han, S.-F. Yin and
L.-B. Han, Adv. Synth. Catal., 2014, 356, 765–769.
In summary, we have developed copper(I) hydride-mediated
transfer hydrogenation reactions employing ammonia borane
(H3NBH3) as a H2 equivalent. Alkynes can be converted into the
corresponding alkenes with high Z-selectivities in transfer
semihydrogenations. Also, the protocol enables a conjugate transfer
hydrogenation of enoates. An air-stable and preactivated copper(I)
hydroxide/NHC complex is used, circumventing the need for
generally common in situ activation of the copper catalyst. We
think that these results could be of importance with foresight
to the use of readily available transition metal catalysts (such as
copper) for transfer hydrogenations.
This research was supported by the Fonds der Chemischen
Industrie (Liebig-Stipendium for J. F. T.) and the German Academic
Exchange Service (DAAD) through a Leistungsstipendium
(for E. K.). F. P. is supported by a predoctoral scholarship of
the Berlin International Graduate School of Natural Sciences
and Engineering (BIG-NSE). We kindly thank Prof. Dr. Martin
Oestreich (TU Berlin) for generous support. Prof. Dr. Gerhard
Erker (WWU Mu¨nster) is thanked for fruitful discussion.
Notes and references
1 C. W. Hamilton, R. T. Baker, A. Staubitz and I. Manners, Chem. Soc.
Rev., 2009, 38, 279–293.
2 A. Staubitz, A. P. M. Robertson and I. Manners, Chem. Rev., 2010,
110, 4079–4124.
22 For alkyne transfer semihydrogenations with ammonia borane and
heterogeneous catalysts, see: (a) D. van der Waals, A. Pettman and
J. M. J. Williams, RSC Adv., 2014, 4, 51845–51849; (b) E. Vasilikogiannaki,
I. Titilas, G. Vassilikogiannakis and M. Stratakis, Chem. Commun., 2015,
51, 2384–2387.
3 H.-L. Jiang and Q. Xu, Catal. Today, 2011, 170, 56–63.
4 F. H. Stephens, V. Pons and R. T. Baker, Dalton Trans., 2007,
2613–2626.
23 See the ESI† for details and additional optimisation (reaction
parameters, Cu catalysts, addition mode) data.
24 G. C. Fortman, A. M. Z. Slawin and S. P. Nolan, Organometallics,
2010, 29, 3966–3972.
5 P. Wang and X.-D. Kang, Dalton Trans., 2008, 5400–5413.
6 J. Yang, A. Sudik, C. Wolverton and D. J. Siegel, Chem. Soc. Rev., 25 For the use of IPrCuOH as the catalyst in carboxylation reactions, see:
2010, 39, 656–675.
(a) I. I. F. Boogaerts, G. C. Fortman, M. R. L. Furst, C. S. J. Cazin and
S. P. Nolan, Angew. Chem., Int. Ed., 2010, 49, 8674–8677; (b) O. Santoro,
F. Lazreg, Y. Minenkov, L. Cavallo and C. S. J. Cazin, Dalton Trans.,
2015, 44, 18138–18144.
7 (a) Y. Tan and X. Yu, RSC Adv., 2013, 3, 23879–23894; (b) N. C.
Smythe and J. C. Gordon, Eur. J. Inorg. Chem., 2010, 509–521.
8 (a) A. Rossin and M. Peruzzini, Chem. Rev., 2016, 116, 8848–8872;
(b) R. Waterman, Chem. Soc. Rev., 2013, 42, 5629–5641; (c) R. J. Less, 26 (a) C. Oger, L. Balas, T. Durand and J.-M. Galano, Chem. Rev., 2013,
´
R. L. Melen and D. S. Wright, RSC Adv., 2012, 2, 2191–2199;
(d) G. Alcaraz and S. Sabo-Etienne, Angew. Chem., Int. Ed., 2010,
49, 7170–7179.
113, 1313–1350; (b) M. Crespo-Quesada, F. Cardenas-Lizana, A.-L.
Dessimoz and L. Kiwi-Minsker, ACS Catal., 2012, 2, 1773–1786;
(c) H. Lindlar, Helv. Chim. Acta, 1952, 35, 446–450.
9 X. Yang, Z. Xie, J. He and L. Yu, Chin. J. Org. Chem., 2015, 35, 603–609. 27 The transfer semihydrogenation of terminal alkynes with the present
10 For selected examples, see: (a) Z. M. Heiden and T. B. Rauchfuss,
J. Am. Chem. Soc., 2007, 129, 14303–14310; (b) N. Blaquiere, S. Diallo-
catalyst leads to mixtures of products with the terminal alkene and a
dimerised 1,3-diene as the major products. See the ESI† for details.
Garcia, S. I. Gorelsky, D. A. Black and K. Fagnou, J. Am. Chem. Soc., 28 Reaction analysis by 11B NMR shows the formation of polyamino-
2008, 130, 14034–14035; (c) Y. Jiang, O. Blacque, T. Fox, C. M. Frech
and H. Berke, Organometallics, 2009, 28, 5493–5504; (d) R. Barrios-
boranes (see the ESI† for details), which indicates the transfer of
1 equiv. of H2 per molecule of ammonia borane. This could account
for the high loadings of ammonia borane required.
´
Francisco and J. J. Garcıa, Appl. Catal., A, 2010, 385, 108–113;
(e) H. Dong and H. Berke, J. Organomet. Chem., 2011, 696, 29 The reduction of ketones with H3NBH3 is most likely an uncatalysed
1803–1808; ( f ) T.-P. Lin and J. C. Peters, J. Am. Chem. Soc., 2013,
135, 15310–15313; (g) J. K. Pagano, J. P. W. Stelmach and
R. Waterman, Dalton Trans., 2015, 44, 12074–12077.
process, see: (a) G. C. Andrews and T. C. Crawford, Tetrahedron Lett.,
1980, 21, 693–696; (b) G. C. Andrews, Tetrahedron Lett., 1980, 21,
697–700; (c) L. Shi, Y. Liu, Q. Liu, B. Wei and G. Zhang, Green Chem.,
2012, 14, 1372–1375.
11 For the use of ammonia borane as the H2 donor in transfer
hydrogenations with alkynes and/or alkenes, see for example: 30 Even though varying amounts of H3NBH3 are necessary in these
´
(a) R. Barrios-Francisco and J. J. Garcıa, Appl. Catal., A, 2010, 385,
transformations, it should be noted that from a practical perspec-
tive, the exact amount required can be determined by in situ analysis
of the reaction: later addition of further equivalents of H3NBH3 is
possible, as the catalyst remains active in solution.
108–113; (b) M. E. Sloan, A. Staubitz, K. Lee and I. Manners, Eur.
J. Org. Chem., 2011, 672–675; (c) C. E. Hartmann, V. Jurcık, O. Songis
and C. S. J. Cazin, Chem. Commun., 2013, 49, 1005–1007; (d) S. Fu,
ˇ´
Chem. Commun.
This journal is ©The Royal Society of Chemistry 2016