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DOI: 10.1039/C5CC09162D
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Received 00th January 20xx, Accepted 00th January 20xx
a
a,
Sharareh Bagherzadeh and Neal P. Mankad *
DOI: 10.1039/x0xx00000x www.rsc.org/
A readily available copper carbene complex, (IPr)CuOtBu, catalyses the hydroboration of ketones and aldehydes even at very low catalyst loadings (0.1 mol%), in some cases with turnover -1 frequencies exceeding 6000 h . Carbonyl reduction occurs selectivitely in the presence of other reducible functional groups including alkenes, nitriles, esters, and alkyl chlorides. Reduction of carbonyl compounds is an effective strategy for synthesizing alcohols, and catalytic hydrosilylation and hydroboration represent methods that can be conducted under mild conditions as alternatives to using flammable and pressurized H2 or hazardous metal-hydride reductants. In comparison to catalytic hydrosilylation, carbonyl 1 hydroboration catalysis is surprisingly underdeveloped. Because silyl groups and boryl groups represent orthogonal alcohol protecting groups, further advancement of catalytic hydroboration would add significantly to the synthetic toolkit. Hydroboration of organic C=O groups with benign reagents such as pinacolborane (HBpin) and catecholborane (HBcat) has 2-6 7-11 12,13 been catalysed with transition metals (Ti, Zn, and Ru ) 14-16 17 18 and with main group elements (Mg, P, Ga, Ge, and 19 Sn ). In selected cases, modest to good levels of 3,4,6-9,11,18 enantioselectivity were achieved using chiral ligands, although further development of stereoselectivity is needed. 20 Readily available copper carbene catalysts, such as 21 (IPr)CuOtBu (IPr = N,N’-bis(2,6-diisopropylphenyl)imidazol-2ylidene) which can be generated in situ from air-stable (IPr)CuCl, have been explored extensively for hydrosilylation 22-31 reactions. Furthermore, the same catalysts are active for 32 33 hydroboration of CO2 and for diboration of aldehydes. Therefore, we were surprised to find that no reports exist for hydroboration of carbonyl compounds by copper carbene catalysis. During our on-going studies of bimetallic reduction 34 reactions of small molecules, we have discovered that (IPr)CuOtBu is an extremely efficient catalyst for
hydroboration of ketones and aldehydes with HBpin. Here we highlight the impressive catalyst loadings (0.1 mol%) and -1 turnover frequencies (>6000 h ) that can be achieved for various ketone and aldehyde substrates in the presence of other reducible functional groups. Given the recent development of chiral copper carbenes by several research 23,35-40 groups, this communication provides the basis for future development of C=O hydroboration reactions that are both efficient and stereoselective. During the course of studying our group’s bimetallic 34 hydroboration catalysts, we discovered that 10 mol% loading of (IPr)CuOtBu catalyses ketone hydroboration to quantitative conversion within minutes. Using the acetophenone derivative 1 as a test substrate (Table 1), we tried lower catalyst loadings and ultimately determined that quantitative hydroboration with HBpin was achieved within 10 min even at 0.1 mol% loading. Using the same conditions (room temperature, 10 min, 0.1 mol% catalyst, 1.0 eq. HBpin) we tested various other ketone substrates. The more electron deficient acetophenone derivative 2 also underwent quantitative hydroboration, while the more electron rich acetophenone derivative 3 produced the hydroboration product in lower yield. Similarly, the more sterically hindered ketones 4 and 5 gave moderate yields under these conditions. Interestingly, aldehyde 6 also underwent hydroboration with moderate yield. Because the reaction time was not optimized for each individual substrate, these yields likely reflect relative reaction rates rather than maximum yields. As evidence for this, we note that all reactions approached quantitative conversion when reaction times were increased to 1 h (Table 1).
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Extremely Efficient Hydroboration of Ketones and Aldehydes by Copper Carbene Catalysis†
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Table 1. Hydroboration of carbonyl compounds by copper carbene catalysis
HBpin (1.0 eq.) (IPr)CuOtBu (0.1 mol%)
O R'
R
C6D 6, room temperature
R'
iPr
iPr
N
N
O HBpin = HB
IPr = O iPr
Published on 08 February 2016. Downloaded by New York University on 08/02/2016 15:30:56.
I
Substrate O Me
Yield (%) at 10 min 98
F 3C
HBpin OBpin
MeO
O
O
R
H
R'
Bpin R' R
O
O
R'
(IPr)Cu
R
H TS1
TS2
55
94
HBpin
(IPr)Cu
O
R' R
Me
5
Figure 1. Proposed mechanism for hydroboration by copper carbene catalysis
49
94 1
O
62
87
92
94
87
96
H
6
O Me I
7
a
95
(IPr)CuH
R'
Me
O
8
46
R
(IPr)Cu
4
>99
O
Br
94 Me
3
O
2
Yield (%) at 1 h >99
a
(IPr)CuOtBu
1
a
iPr
O H
Determined by 1H NMR integration against an internal standard (mesitylene).
A σ-bond metathesis type mechanism is likely operative here (Figure 1), proposed in analogy to the accepted 22-29 mechanism for hydrosilylation by copper carbene catalysis. First, the (IPr)CuOtBu precatalyst reacts with HBpin to generate a copper-hydride intermediate, which takes the 21 dimeric form [(IPr)Cu]2(µ-H)2 in the solid state and which may 28 41 be either monomeric or dimeric in solution under the reaction conditions. Second, the carbonyl substrate inserts into the Cu-H bond via transition state TS1 to generate the corresponding copper-alkoxide intermediate. Finally, reaction with HBpin via σ-bond metathesis transition state TS2 produces the alkoxyboronate ester product and regenerates the copper-hydride species for further reaction. In the related hydrosilylation catalysis with copper carbenes, TS1 is thought to be primarily under steric control, the Si analogue of TS2 is thought to be primarily under electronic control, and the two barrier heights are generally similar enough that the ratedetermining step changes based on the natures of the silane 28 reductant and the carbonyl substrate. Both sterically hindered substrates and electron-rich substrates give slow catalytic rates for the hydroboration reaction (Table 1), and further studies are necessary to determine whether TS1, TS2,
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
ChemComm Accepted Manuscript
R
OBpin
Gratifyingly, even the ortho-substituted View arylcarbonyl Article Online DOI: 10.1039/C5CC09162D complexes 7 and 8 underwent hydroboration to high conversions under these conditions (Table 1). Because this method produces no byproducts and utilizes catalyst loadings below the detection limits of NMR spectroscopy, the reduction products can be isolated in spectroscopically pure form simply by removal of volatiles in vacuo (see ESI). However, selectivity between ketones and aldehydes is poor, as evidenced by the reduction of 4-acetylbenzaldehyde, which reacted efficiently but was unselective for ketone vs. aldehyde hydroboration (see Figure S9).
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COMMUNICATION
or both are rate determining and responsible for these observed effects.
4
Table 2. Robustness of ketone hydroboration towards reducible functional groups
Me
I
5
HBpin (1.0 eq.) additive (1.0 eq.) (IPr)CuOtBu (0.1 mol%)
O
C6D 6, room temperature
1
Additive
OBpin
6
Me I
Yield (%) at a 10 min 81
Yield (%) at 1 a h >99
8
7
16
10
70 71
90 84
11
Published on 08 February 2016. Downloaded by New York University on 08/02/2016 15:30:56.
7
9
Me
N
O OMe
12 13
Cl
N
81
87
46
99
15
a
14
Determined by 1H NMR integration against an internal standard (mesitylene).
16
Lastly, to determine whether carbonyl groups can undergo hydroboration in the presence of other reducible functional groups, we conducted a brief additive screen as pioneered by 42 Glorius. Substrate 1 was subjected to the standard reaction conditions in the presence of different additives (1.0 eq.) as indicated in Table 2. Hydroboration of the carbonyl group in 1 was observed in the presence of alkene, nitrile, ester, and alkyl chloride functional groups. In all of these cases, the additive was detected in the product mixture and had not been reduced. On the other hand, the presence of an alkyne functional group poisoned the carbonyl reduction. Alkyne 43,44 hydroboration by copper carbene catalysis apparently outcompetes even the highly efficient ketone hydroboration reaction reported here. Additives with coordinating functional groups – especially pyridine – slow the rate of catalysis but do no prevent the reaction from reaching high conversion at longer reaction times (Table 2). Funding for this study was provided by the National Science Foundation (CHE-1362294) and by an Alfred P. Sloan Research Fellowship (to N.P.M.). The authors thank Malkanthi Karunananda for verifying reproducibility of selected catalytic results. The authors also are grateful to the reviewers of this manuscript for helpful suggestions.
17
Notes and references
31
1 2
32
3
C. C. Chong and R. Kinjo, ACS Catal., 2015, 5, 3238–3259. C. W. Lindsley and M. DiMare, Tetrahedron Lett., 1994, 35, 5141–5144. G. Giffels, C. Dreisbach, U. Kragl, M. Weigerding, H.
18 19 20 21 22 23 24 25 26 27 28 29 30
33
Waldmann and C. Wandrey, Angew. Chem. Int. Ed. Engl., View Article Online DOI: 10.1039/C5CC09162D 1995, 34, 2005–2006. F. Almqvist, L. Torstensson, A. Gudmundsson and T. Frejd, Angew. Chem. Int. Ed. Engl., 1997, 36, 376–377. A. A. Oluyadi, S. Ma and C. N. Muhoro, Organometallics, 2013, 32, 70–78. I. Sarvary, F. Almqvist and T. Frejd, Chem. Eur. J., 2001, 7, 2158–2166. M. Bandini, P. G. Cozzi, M. de Angelis and A. Umani-Ronchi, Tetrahedron Lett., 2000, 41, 1601–1605. S. G. Roh, J. U. Yoon and J. H. Jeong, Polyhedron, 2004, 23, 2063–2067. S. G. Roh, Y. C. Park, D. K. Park, T. J. Kim and J. H. Jeong, Polyhedron, 2001, 20, 1961–1965. P. A. Lummis, M. R. Momeni, M. W. Lui, R. McDonald, M. J. Ferguson, M. Miskolzie, A. Brown and E. Rivard, Angew. Chem. Int. Ed., 2014, 53, 9347–9351. M. Locatelli and P. G. Cozzi, Angew. Chem. Int. Ed., 2003, 42, 4928–4930. A. Kaithal, B. Chatterjee and C. Gunanathan, Org. Lett., 2015, 17, 4790–4793. L. Koren-Selfridge, H. N. Londino, J. K. Vellucci, B. J. Simmons, C. P. Casey and T. B. Clark, Organometallics, 2009, 28, 2085– 2090. N. L. Lampland, M. Hovey, D. Mukherjee and A. D. Sadow, ACS Catal., 2015, 5, 4219–4226. M. Arrowsmith, T. J. Hadlington, M. S. Hill and G. KociokKöhn, Chem. Commun., 2012, 48, 4567–4. D. Mukherjee, A. Ellern and A. D. Sadow, Chem. Sci., 2014, 5, 959–964. C. C. Chong, H. Hirao and R. Kinjo, Angew. Chem. Int. Ed., 2015, 54, 190–194. A. J. Blake, A. Cunningham, A. Ford, S. J. Teat and S. Woodward, Chem. Eur. J., 2000, 6, 3586–3594. T. J. Hadlington, M. Hermann, G. Frenking and C. Jones, J. Am. Chem. Soc., 2014, 136, 3028–3031. S. Díez-González and S. Nolan, Synlett, 2007, 14, 2158–2167. N. P. Mankad, D. S. Laitar and J. P. Sadighi, Organometallics, 2004, 23, 3369–3371. H. Kaur, F. K. Zinn, E. D. Stevens and S. P. Nolan, Organometallics, 2004, 23, 1157–1160. A. Albright and R. E. Gawley, J. Am. Chem. Soc., 2011, 133, 19680–19683. S. Díez-González, H. Kaur, F. K. Zinn, E. D. Stevens and S. P. Nolan, J. Org. Chem., 2005, 70, 4784–4796. S. Díez-González, N. M. Scott and S. P. Nolan, Organometallics, 2006, 25, 2355–2358. S. Díez-González, E. C. Escudero-Adán, J. Benet-Buchholz, E. D. Stevens, A. M. Z. Slawin and S. P. Nolan, Dalton Trans., 2010, 39, 7595–7606. S. Díez-González, E. D. Stevens, N. M. Scott, J. L. Petersen and S. P. Nolan, Chem. Eur. J., 2008, 14, 158–168. T. Vergote, F. Nahra, A. Merschaert, O. Riant, D. Peeters and T. Leyssens, Organometallics, 2014, 33, 1953–1963. J. Yun, D. Kim and H. Yun, Chem. Commun., 2005, 5181–5183. T. Vergote, F. Nahra, D. Peeters, O. Riant and T. Leyssens, J. Organomet. Chem., 2013, 730, 95–103. H. Ito, T. Ishizuka, T. Okumura and H. Yamanaka, J. Organomet. Chem., 1999, 730, 95–103. R. Shintani and K. Nozaki, Organometallics, 2013, 32, 2459– 2462. D. S. Laitar, E. Y. Tsui and J. P. Sadighi, J. Am. Chem. Soc.,
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34 35 36 37 38
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39 40 41 42 43 44
Journal Name
2006, 128, 11036–11037. S. Bagherzadeh and N. P. Mankad, J. Am. Chem. Soc., 2015, 137, 10898–10901. J. J. Van Veldhuizen, J. E. Campbell, R. E. Giudici and A. H. Hoveyda, J. Am. Chem. Soc., 2005, 127, 6877–6882. A. Albright, D. Eddings, R. Black, C. J. Welch, N. N. Gerasimchuk and R. E. Gawley, J. Org. Chem., 2011, 76, 7341–7351. J. M. O’Brien, K.-S. Lee and A. H. Hoveyda, J. Am. Chem. Soc., 2010, 132, 10630–10633. J. K. Park, H. H. Lackey, M. D. Rexford, K. Kovnir, M. Shatruk and D. T. McQuade, Org. Lett., 2010, 12, 5008–5011. K. B. Selim, Y. Matsumoto, K.-I. Yamada and K. Tomioka, Angew. Chem. Int. Ed., 2009, 48, 8733–8735. K. Takatsu, R. Shintani and T. Hayashi, Angew. Chem. Int. Ed., 2011, 50, 5548–5552. S. R. Parmelee, T. J. Mazzacano, Y. Zhu, N. P. Mankad and J. A. Keith, ACS Catal., 2015, 5, 3689–3699. K. D. Collins and F. Glorius, Nature Chem., 2013, 5, 597–601. B. H. Lipshutz, Z. V. Bošković and D. H. Aue, Angew. Chem. Int. Ed., 2008, 47, 10183–10186. K. Semba, T. Fujihara, J. Terao and Y. Tsuji, Chem. Eur. J., 2012, 18, 4179–4184.
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This article can be cited before page numbers have been issued, to do this please use: S. Bagherzadeh and N. Mankad, Chem. Commun., 2016, DOI: 10.1039/C5CC09162D.
This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.
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Received 00th January 20xx, Accepted 00th January 20xx
a
a,
Sharareh Bagherzadeh and Neal P. Mankad *
DOI: 10.1039/x0xx00000x www.rsc.org/
A readily available copper carbene complex, (IPr)CuOtBu, catalyses the hydroboration of ketones and aldehydes even at very low catalyst loadings (0.1 mol%), in some cases with turnover -1 frequencies exceeding 6000 h . Carbonyl reduction occurs selectivitely in the presence of other reducible functional groups including alkenes, nitriles, esters, and alkyl chlorides. Reduction of carbonyl compounds is an effective strategy for synthesizing alcohols, and catalytic hydrosilylation and hydroboration represent methods that can be conducted under mild conditions as alternatives to using flammable and pressurized H2 or hazardous metal-hydride reductants. In comparison to catalytic hydrosilylation, carbonyl 1 hydroboration catalysis is surprisingly underdeveloped. Because silyl groups and boryl groups represent orthogonal alcohol protecting groups, further advancement of catalytic hydroboration would add significantly to the synthetic toolkit. Hydroboration of organic C=O groups with benign reagents such as pinacolborane (HBpin) and catecholborane (HBcat) has 2-6 7-11 12,13 been catalysed with transition metals (Ti, Zn, and Ru ) 14-16 17 18 and with main group elements (Mg, P, Ga, Ge, and 19 Sn ). In selected cases, modest to good levels of 3,4,6-9,11,18 enantioselectivity were achieved using chiral ligands, although further development of stereoselectivity is needed. 20 Readily available copper carbene catalysts, such as 21 (IPr)CuOtBu (IPr = N,N’-bis(2,6-diisopropylphenyl)imidazol-2ylidene) which can be generated in situ from air-stable (IPr)CuCl, have been explored extensively for hydrosilylation 22-31 reactions. Furthermore, the same catalysts are active for 32 33 hydroboration of CO2 and for diboration of aldehydes. Therefore, we were surprised to find that no reports exist for hydroboration of carbonyl compounds by copper carbene catalysis. During our on-going studies of bimetallic reduction 34 reactions of small molecules, we have discovered that (IPr)CuOtBu is an extremely efficient catalyst for
hydroboration of ketones and aldehydes with HBpin. Here we highlight the impressive catalyst loadings (0.1 mol%) and -1 turnover frequencies (>6000 h ) that can be achieved for various ketone and aldehyde substrates in the presence of other reducible functional groups. Given the recent development of chiral copper carbenes by several research 23,35-40 groups, this communication provides the basis for future development of C=O hydroboration reactions that are both efficient and stereoselective. During the course of studying our group’s bimetallic 34 hydroboration catalysts, we discovered that 10 mol% loading of (IPr)CuOtBu catalyses ketone hydroboration to quantitative conversion within minutes. Using the acetophenone derivative 1 as a test substrate (Table 1), we tried lower catalyst loadings and ultimately determined that quantitative hydroboration with HBpin was achieved within 10 min even at 0.1 mol% loading. Using the same conditions (room temperature, 10 min, 0.1 mol% catalyst, 1.0 eq. HBpin) we tested various other ketone substrates. The more electron deficient acetophenone derivative 2 also underwent quantitative hydroboration, while the more electron rich acetophenone derivative 3 produced the hydroboration product in lower yield. Similarly, the more sterically hindered ketones 4 and 5 gave moderate yields under these conditions. Interestingly, aldehyde 6 also underwent hydroboration with moderate yield. Because the reaction time was not optimized for each individual substrate, these yields likely reflect relative reaction rates rather than maximum yields. As evidence for this, we note that all reactions approached quantitative conversion when reaction times were increased to 1 h (Table 1).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins
ChemComm Accepted Manuscript
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Extremely Efficient Hydroboration of Ketones and Aldehydes by Copper Carbene Catalysis†
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Journal Name
Table 1. Hydroboration of carbonyl compounds by copper carbene catalysis
HBpin (1.0 eq.) (IPr)CuOtBu (0.1 mol%)
O R'
R
C6D 6, room temperature
R'
iPr
iPr
N
N
O HBpin = HB
IPr = O iPr
Published on 08 February 2016. Downloaded by New York University on 08/02/2016 15:30:56.
I
Substrate O Me
Yield (%) at 10 min 98
F 3C
HBpin OBpin
MeO
O
O
R
H
R'
Bpin R' R
O
O
R'
(IPr)Cu
R
H TS1
TS2
55
94
HBpin
(IPr)Cu
O
R' R
Me
5
Figure 1. Proposed mechanism for hydroboration by copper carbene catalysis
49
94 1
O
62
87
92
94
87
96
H
6
O Me I
7
a
95
(IPr)CuH
R'
Me
O
8
46
R
(IPr)Cu
4
>99
O
Br
94 Me
3
O
2
Yield (%) at 1 h >99
a
(IPr)CuOtBu
1
a
iPr
O H
Determined by 1H NMR integration against an internal standard (mesitylene).
A σ-bond metathesis type mechanism is likely operative here (Figure 1), proposed in analogy to the accepted 22-29 mechanism for hydrosilylation by copper carbene catalysis. First, the (IPr)CuOtBu precatalyst reacts with HBpin to generate a copper-hydride intermediate, which takes the 21 dimeric form [(IPr)Cu]2(µ-H)2 in the solid state and which may 28 41 be either monomeric or dimeric in solution under the reaction conditions. Second, the carbonyl substrate inserts into the Cu-H bond via transition state TS1 to generate the corresponding copper-alkoxide intermediate. Finally, reaction with HBpin via σ-bond metathesis transition state TS2 produces the alkoxyboronate ester product and regenerates the copper-hydride species for further reaction. In the related hydrosilylation catalysis with copper carbenes, TS1 is thought to be primarily under steric control, the Si analogue of TS2 is thought to be primarily under electronic control, and the two barrier heights are generally similar enough that the ratedetermining step changes based on the natures of the silane 28 reductant and the carbonyl substrate. Both sterically hindered substrates and electron-rich substrates give slow catalytic rates for the hydroboration reaction (Table 1), and further studies are necessary to determine whether TS1, TS2,
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
ChemComm Accepted Manuscript
R
OBpin
Gratifyingly, even the ortho-substituted View arylcarbonyl Article Online DOI: 10.1039/C5CC09162D complexes 7 and 8 underwent hydroboration to high conversions under these conditions (Table 1). Because this method produces no byproducts and utilizes catalyst loadings below the detection limits of NMR spectroscopy, the reduction products can be isolated in spectroscopically pure form simply by removal of volatiles in vacuo (see ESI). However, selectivity between ketones and aldehydes is poor, as evidenced by the reduction of 4-acetylbenzaldehyde, which reacted efficiently but was unselective for ketone vs. aldehyde hydroboration (see Figure S9).
ChemComm Please do not adjust margins
Page 3 of 4
COMMUNICATION
or both are rate determining and responsible for these observed effects.
4
Table 2. Robustness of ketone hydroboration towards reducible functional groups
Me
I
5
HBpin (1.0 eq.) additive (1.0 eq.) (IPr)CuOtBu (0.1 mol%)
O
C6D 6, room temperature
1
Additive
OBpin
6
Me I
Yield (%) at a 10 min 81
Yield (%) at 1 a h >99
8
7
16
10
70 71
90 84
11
Published on 08 February 2016. Downloaded by New York University on 08/02/2016 15:30:56.
7
9
Me
N
O OMe
12 13
Cl
N
81
87
46
99
15
a
14
Determined by 1H NMR integration against an internal standard (mesitylene).
16
Lastly, to determine whether carbonyl groups can undergo hydroboration in the presence of other reducible functional groups, we conducted a brief additive screen as pioneered by 42 Glorius. Substrate 1 was subjected to the standard reaction conditions in the presence of different additives (1.0 eq.) as indicated in Table 2. Hydroboration of the carbonyl group in 1 was observed in the presence of alkene, nitrile, ester, and alkyl chloride functional groups. In all of these cases, the additive was detected in the product mixture and had not been reduced. On the other hand, the presence of an alkyne functional group poisoned the carbonyl reduction. Alkyne 43,44 hydroboration by copper carbene catalysis apparently outcompetes even the highly efficient ketone hydroboration reaction reported here. Additives with coordinating functional groups – especially pyridine – slow the rate of catalysis but do no prevent the reaction from reaching high conversion at longer reaction times (Table 2). Funding for this study was provided by the National Science Foundation (CHE-1362294) and by an Alfred P. Sloan Research Fellowship (to N.P.M.). The authors thank Malkanthi Karunananda for verifying reproducibility of selected catalytic results. The authors also are grateful to the reviewers of this manuscript for helpful suggestions.
17
Notes and references
31
1 2
32
3
C. C. Chong and R. Kinjo, ACS Catal., 2015, 5, 3238–3259. C. W. Lindsley and M. DiMare, Tetrahedron Lett., 1994, 35, 5141–5144. G. Giffels, C. Dreisbach, U. Kragl, M. Weigerding, H.
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Waldmann and C. Wandrey, Angew. Chem. Int. Ed. Engl., View Article Online DOI: 10.1039/C5CC09162D 1995, 34, 2005–2006. F. Almqvist, L. Torstensson, A. Gudmundsson and T. Frejd, Angew. Chem. Int. Ed. Engl., 1997, 36, 376–377. A. A. Oluyadi, S. Ma and C. N. Muhoro, Organometallics, 2013, 32, 70–78. I. Sarvary, F. Almqvist and T. Frejd, Chem. Eur. J., 2001, 7, 2158–2166. M. Bandini, P. G. Cozzi, M. de Angelis and A. Umani-Ronchi, Tetrahedron Lett., 2000, 41, 1601–1605. S. G. Roh, J. U. Yoon and J. H. Jeong, Polyhedron, 2004, 23, 2063–2067. S. G. Roh, Y. C. Park, D. K. Park, T. J. Kim and J. H. Jeong, Polyhedron, 2001, 20, 1961–1965. P. A. Lummis, M. R. Momeni, M. W. Lui, R. McDonald, M. J. Ferguson, M. Miskolzie, A. Brown and E. Rivard, Angew. Chem. Int. Ed., 2014, 53, 9347–9351. M. Locatelli and P. G. Cozzi, Angew. Chem. Int. Ed., 2003, 42, 4928–4930. A. Kaithal, B. Chatterjee and C. Gunanathan, Org. Lett., 2015, 17, 4790–4793. L. Koren-Selfridge, H. N. Londino, J. K. Vellucci, B. J. Simmons, C. P. Casey and T. B. Clark, Organometallics, 2009, 28, 2085– 2090. N. L. Lampland, M. Hovey, D. Mukherjee and A. D. Sadow, ACS Catal., 2015, 5, 4219–4226. M. Arrowsmith, T. J. Hadlington, M. S. Hill and G. KociokKöhn, Chem. Commun., 2012, 48, 4567–4. D. Mukherjee, A. Ellern and A. D. Sadow, Chem. Sci., 2014, 5, 959–964. C. C. Chong, H. Hirao and R. Kinjo, Angew. Chem. Int. Ed., 2015, 54, 190–194. A. J. Blake, A. Cunningham, A. Ford, S. J. Teat and S. Woodward, Chem. Eur. J., 2000, 6, 3586–3594. T. J. Hadlington, M. Hermann, G. Frenking and C. Jones, J. Am. Chem. Soc., 2014, 136, 3028–3031. S. Díez-González and S. Nolan, Synlett, 2007, 14, 2158–2167. N. P. Mankad, D. S. Laitar and J. P. Sadighi, Organometallics, 2004, 23, 3369–3371. H. Kaur, F. K. Zinn, E. D. Stevens and S. P. Nolan, Organometallics, 2004, 23, 1157–1160. A. Albright and R. E. Gawley, J. Am. Chem. Soc., 2011, 133, 19680–19683. S. Díez-González, H. Kaur, F. K. Zinn, E. D. Stevens and S. P. Nolan, J. Org. Chem., 2005, 70, 4784–4796. S. Díez-González, N. M. Scott and S. P. Nolan, Organometallics, 2006, 25, 2355–2358. S. Díez-González, E. C. Escudero-Adán, J. Benet-Buchholz, E. D. Stevens, A. M. Z. Slawin and S. P. Nolan, Dalton Trans., 2010, 39, 7595–7606. S. Díez-González, E. D. Stevens, N. M. Scott, J. L. Petersen and S. P. Nolan, Chem. Eur. J., 2008, 14, 158–168. T. Vergote, F. Nahra, A. Merschaert, O. Riant, D. Peeters and T. Leyssens, Organometallics, 2014, 33, 1953–1963. J. Yun, D. Kim and H. Yun, Chem. Commun., 2005, 5181–5183. T. Vergote, F. Nahra, D. Peeters, O. Riant and T. Leyssens, J. Organomet. Chem., 2013, 730, 95–103. H. Ito, T. Ishizuka, T. Okumura and H. Yamanaka, J. Organomet. Chem., 1999, 730, 95–103. R. Shintani and K. Nozaki, Organometallics, 2013, 32, 2459– 2462. D. S. Laitar, E. Y. Tsui and J. P. Sadighi, J. Am. Chem. Soc.,
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2006, 128, 11036–11037. S. Bagherzadeh and N. P. Mankad, J. Am. Chem. Soc., 2015, 137, 10898–10901. J. J. Van Veldhuizen, J. E. Campbell, R. E. Giudici and A. H. Hoveyda, J. Am. Chem. Soc., 2005, 127, 6877–6882. A. Albright, D. Eddings, R. Black, C. J. Welch, N. N. Gerasimchuk and R. E. Gawley, J. Org. Chem., 2011, 76, 7341–7351. J. M. O’Brien, K.-S. Lee and A. H. Hoveyda, J. Am. Chem. Soc., 2010, 132, 10630–10633. J. K. Park, H. H. Lackey, M. D. Rexford, K. Kovnir, M. Shatruk and D. T. McQuade, Org. Lett., 2010, 12, 5008–5011. K. B. Selim, Y. Matsumoto, K.-I. Yamada and K. Tomioka, Angew. Chem. Int. Ed., 2009, 48, 8733–8735. K. Takatsu, R. Shintani and T. Hayashi, Angew. Chem. Int. Ed., 2011, 50, 5548–5552. S. R. Parmelee, T. J. Mazzacano, Y. Zhu, N. P. Mankad and J. A. Keith, ACS Catal., 2015, 5, 3689–3699. K. D. Collins and F. Glorius, Nature Chem., 2013, 5, 597–601. B. H. Lipshutz, Z. V. Bošković and D. H. Aue, Angew. Chem. Int. Ed., 2008, 47, 10183–10186. K. Semba, T. Fujihara, J. Terao and Y. Tsuji, Chem. Eur. J., 2012, 18, 4179–4184.
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