CuCl-K2CO3-catalyzed highly selective borylcupration of internal alkynes - Ligand effect

Article abstract of DOI:10.1039/c2ob26147b

An efficient and practical copper-catalyzed highly regio- and stereoselective borylcupration of internal alkynes with bis(pinacolato)diboron using a catalytic amount of K₂CO₃ as base producing Z-alkenylboron compounds has been demonstrated by applying the ligand effect: commercially available electron-rich tris(p-methoxyphenyl) phosphine ensures a smooth and efficient reaction. Functionalized alkynes, such as propargylic alcohols and derivatives as well as N-propargyl tosylamide, may also be used with excellent selectivity.

Full text of DOI:10.1039/c2ob26147b

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CuCl/K2CO3-catalyzed highly selective borylcupration of internal alkynes-ligand
effect
Weiming Yuana and Shengming Ma*a,b
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
to promote this borylcupration reaction (entries 6ꢀ8). Thus, we
chose 5 mol% CuCl, 6 mol% P(C6H4OMeꢀp)3, and 20 mol%
50 K2CO3 as the standard conditions for further study on this
borylcupration reaction (entry 4).
An efficient and practical copper-catalyzed highly regio- and
stereoselective borylcupration of internal alkynes with
bis(pinacolato)diboron using a catalytic amount of K2CO3 as
base producing Z-alkenylboron compounds has been
10 demonstrated by applying the ligand effect: commerically
available electron-rich tris(p-methoxyphenyl) phosphine
ensures a smooth and efficient reaction. Functionalized
alkynes, such as propargylic alcohols and derivatives as well
as N-propargyl tosylamide, may also be used with an excellent
15 selectivity.
Table 1 Optimization of reaction conditions for copperꢀcatalyzed regioꢀ
and stereoselective borylcupration of internal alkynesa
Vinylboron compounds are highly important synthetic
intermediates widely utilized in transition metalꢀcatalyzed
crossꢀcoupling reactions and other synthetically useful
transformations.1ꢀ4 Transition metalꢀcatalyzed addition
20 reactions of boronꢀcontaining reagents to unsaturated carbonꢀ
carbon bonds have become an important strategy for the
synthesis of these compounds.5ꢀ8 Among which, recently
developed catalytic borylcupration of internal alkynes with
commercial bis(pinacolato)diboron followed by protonolysis
25 is an efficient methodology for the stereoselective preparation
of alkenyl boranes with a high regioselectivity.6 However,
moistureꢀ and airꢀsensitive NaOtꢀBu or KOtꢀBu as base was
used in these reactions. In this paper, we wish to report a
CuClꢀcatalyzed practical protocol for such a purpose by using
Entry
Ligand
PPh3
TFP
Base
K2CO3
K2CO3
K2CO3
K2CO3
ꢀ
Na2CO3
NaOAc
K3PO4
Time (h) NMR yield (%)
1
2
3
4
5
6
7
8
23
23
16
15
43
24
24
12
57 (38)b
61 (31)b
94
P(oꢀtoyl)3
P(C6H4OMe-p)3
P(C6H4OMeꢀp)3
P(C6H4OMeꢀp)3
P(C6H4OMeꢀp)3
P(C6H4OMeꢀp)3
98
0 (95)b
86 (11)b
44 (43)b
95
a
Reaction conditions: 0.5 mmol of internal alkynes, 0.6 mmol of
bis(pinacolato)diboron, 5 mol% CuCl, 6 mol% Ligand, 20 mol% base and
1.0 mmol of iꢀPrOH in 2 mL of Et2O at rt. b The number in the parenthesis
is the recovery of starting material.
55
30
a catalytic amount of K2CO3 as the base with the
With the optimized conditions in hand, we next explored
the scope of the reaction using various disubstituted alkynes.
Firstly, with Ar = Ph, different alkyl group R may be applied
to afford the corresponding products in good yields with
commercially available electronꢀrich P(C6H4OMeꢀp)3 as the
ligand bearing a nice substrate scope.
With the purpose of avoiding the use of NaOtꢀBu, initially,
we chose 20 mol% of the easyꢀtoꢀhandle and readily available
60 B(pin) always adding to the carbon atom connected to the
alkyl group with an exclusive Zꢀgeometry (Table 2, entries 1ꢀ
4); both electronꢀdonating substituents, such as pꢀMe, pꢀEt, pꢀ
(nꢀBu) or pꢀOMe, and electronꢀwithdrawing groups such as pꢀ
F or mꢀCl or oꢀCl, may be accommodated in the aryl group
65 (entries 5ꢀ12); heteroaromatic substituted internal alkynes
such as 2ꢀthienylꢀ1ꢀpropyne (1m) and 2ꢀ(1ꢀhexynyl)pyridine
(1n) were examined as well with the same excellent regioꢀ and
stereoselectivity (entries 13ꢀ14). The structure of Zꢀ2j was
confirmed by the Xꢀray single crystal diffraction study (Fig.
70 1).9
35 K2CO3 as base: with PPh3 as the ligand, the borylcupration
reaction at room temperature with 1a afforded Zꢀ2a in 57%
yield with 38% recovery of 1a within 23 h, indicating a very
slow reaction (Table 1, entry 1)! Subsequently, we
investigated the ligand effect: when more electronꢀdonating
40 ligand such as TFP was used, the yield had slightly increased
with 31% recovery of 1a (entry 2); further increasing
electronꢀdonating ability of the ligand by using P(oꢀtoyl)3 led
to a satisfactory result with no recovery (entry 3); finally, we
were glad to observe that P(C6H4OMeꢀp)3 is even better (entry
45 4). Control experiment showed that this reaction did not
proceed in absence of a base (entry 5); screening other readily
available bases lead to the conclusion that K2CO3 is the best
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Table 2 CuCl/K2CO3ꢀcatalyzed boron additions to various
K2CO3 to complete the reaction (Table 3, entry 4). The
structure of Zꢀ2s was confirmed by NOE experiment and the
Xꢀray single crystal diffraction study (Fig. 2),10
internal aryl alkynesa
Table 3 CuCl/K2CO3ꢀcatalyzed borylcupration of internal alkynes with a
25 tꢀbutyl groupa
Entry
Ar
R
Time (h) Yield of Zꢀ2
(%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Ph
Ph
Ph
Ph
CH3 (1a)
nꢀC3H7 (1b)
nꢀC4H9 (1c)
nꢀC6H13 (1d)
CH3 (1e)
15
12
15
17
15
21
36
36
11
12
12
11
12
10
87 (Z-2a)
86 (Z-2b)
87 (Z-2c)
86 (Z-2d)
88 (Z-2e)
83 (Z-2f)
82 (Z-2g)
82 (Z-2h)
85 (Z-2i)
85 (Z-2j)
83 (Z-2k)
78 (Z-2l)
83 (Z-2m)
75 (Z-2n)
Entry
Ar
Time (h)
Yield of Zꢀ2 (%)b
76 (Z-2p)
pꢀMeC6H4
pꢀEtC6H4
pꢀnꢀBuC6H4
pꢀMeOC6H4
pꢀFC6H4
pꢀBrC6H4
mꢀClC6H4
oꢀClC6H4
2ꢀthienyl
2ꢀpyridinyl
1
2
Ph (1p)
36
24
22
22
38
CH3 (1f)
pꢀAcC6H4 (1q)
pꢀFC6H4 (1r)
pꢀMeC6H4 (1s)
1ꢀnaphthyl (1t)
74 (Z-2q)
CH3 (1g)
CH3 (1h)
CH3 (1i)
CH3 (1j)
CH3 (1k)
CH3 (1l)
3
4c
75 (Z-2r)
92 (Z-2s)
5
73 (Z-2t)
a
Reaction conditions: 0.5 mmol of internal alkynes, 0.6 mmol of
bis(pinacolato)diboron, 5 mol% CuCl, 6 mol% P(C6H4OMeꢀp)3, 20
b
mol% K2CO3 and 1.0 mmol of iꢀPrOH in 2 mL of Et2O at rt. Isolated
CH3 (1m)
CH3 (1n)
yield. c The loading of K2CO3 is 40 mol%.
a
Reaction conditions: 0.5 mmol of internal alkynes, 0.6 mmol of
bis(pinacolato)diboron, 5 mol% CuCl, 6 mol% P(C6H4OMeꢀp)3, 20
b
mol% K2CO3 and 1.0 mmol of iꢀPrOH in 2 mL of Et2O at rt. The
yield is the isolated yield.
5
Fig. 1 ORTEP representation of Zꢀ2j.
The reaction of 1,2ꢀbis(pꢀtolyl)ethyne 1o may also proceed
smoothly to afford Zꢀ2o in good yield (eq 1).
Fig. 2 ORTEP representation of Zꢀ2s.
30
Functionalized internal alkynes were also investigated
under these conditions,6d for example, when unprotected 2ꢀ
butylꢀ1ꢀol was used as the substrate, βꢀborylated allylic
alcohol Zꢀ2u was afforded in a high yield with an excellent βꢀ
regioselectivity and Zꢀstereoselectivity (Table 4, entry 1);
10
When sterically demanding tꢀbutyl substituted alkynes 1pꢀ
1t were subjected to the reaction conditions (Table 3), it is
interesting to observe that the regioselectivity is absolutely
inverted with B(pin) adding to the side of arylꢀsubstituent
15 affording the synꢀaddition products exclusively, which is just
opposite to what was reported in the literature with an antiꢀ
selectivity.6b The results showed that the substrates bearing
electronꢀwithdrawing group can increase the reactivity (Table
3, entries 2 and 3); when electronꢀdonating group such as pꢀ
20 Me was installed, it is necessary to increase the loading of
35 propargylic alcohol derivatives such as benzyl or acetylꢀ
protected substrates proved also to be suitable (entries 2ꢀ3);
same selectivity was also observed with NꢀTsꢀprotected
propargylamine (entry 4). These stereodefined functionalized
1ꢀalkenylboronates would not be easily available from the
40 traditional hydroboration and are very useful intermediates for
crossꢀcoupling reaction and other transformations.1ꢀ4
2
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Table 4 CuCl/K2CO3ꢀcatalyzed borylcupration of propargylic derivativesa
3
(a) T. Ohishi, M. Nishiura, Z. Hou, Angew. Chem. Int. Ed.; 2008, 47,
5792; (b) R. Shintani, M. Takeda, Y. T. Soh, T. Ito, T. Hayashi, Org.
Lett.; 2011, 13, 2977; (c) J. Takaya, S. Tadami, K. Ukai, N. Iwasawa,
Org. Lett.; 2008, 10, 2697.
45
50
55
60
65
70
75
80
85
90
4
5
(a) M. Sakai, H. Hayashi, N. Miyaura, Organometallics, 1997, 16,
4229; (b) S. Sakuma, M. Sakai, R. Itooka, N. Miyaura, J. Org. Chem.;
2000, 65, 5951.
Entry
FG
Time (h)
4.5
7
6
4.5
β:α (ratio)b
> 99:1
> 99:1
> 99:1
Yield of Zꢀ2 (%)c
85 (Z-2u)
For reports on catalytic hydroboration of alkenes, see: (a) Y. Lee, A.
H. Hoveyda, J. Am. Chem. Soc.; 2009, 131, 3160; (b) V. Lillo, M. R.
Fructos, J. Ramirez, A. A. C. Braga, F. Maseras, M. M. Diazꢀ
Reguejo, P. J. Pérez, E. Fernández, Chem. –Eur. J.; 2007, 13, 2614;
(c) K. Buegess, M. J. Ohlmeyer, Chem. Rev.; 1991, 91, 1179; (d) C.
Crudden, Y. Hleba, A. Chen, J. Am. Chem. Soc.; 2004, 126, 9200; (e)
S. M. Smith, N. C. Thacker, J. M. Takacs, J. Am. Chem. Soc.; 2008,
130, 3734.
For Cuꢀcatalyzed borylcupration of alkyne with B2(pin)2 see: (a) H. R.
Kim, II. G. Jung, K. Yoo, K. Jang, E. S. Lee, J. Yun, S. U. Son,
Chem. Commun.; 2010, 46, 758; (b) H. R. Kim, J. Yun, Chem.
Commun.; 2011, 47, 2943; (c) H. Jang, A. R. Zhugralin, Y. Lee, A.
H. Hoveyda, J. Am. Chem. Soc.; 2011, 133, 7859; (d) A. L. Moure,
R. G. Arrayás, D. J. Cárdenas, I. Alonso, J. C. Carretero, J. Am.
Chem. Soc.; 2012, 134, 7219. For stoichiometric amouts of a Cu
complex promoted hydroboration of alkynes, see: K. Takahashi, T.
Ishiyama, N. Miyaura, J. Organomet. Chem.; 2001, 625, 47.
For Cuꢀcatalyzed hydroboration of 1,3ꢀenynes with B2(pin)2 see: Y.
Sasaki, Y. Horita, C. M. Zhong, M. Sawamura, H. Ito, Angew. Chem.
Int. Ed.; 2011, 50, 2778.
For reports on diboration of alkynes, see: (a) T. Ishiyama, N.
Matsuda, N. Miyaura, A. Suzuki, J. Am. Chem. Soc.; 1993, 115,
11018; (b) H. Yishida, S. Kawashima, Y. Takemoto, K. Okada, J.
Ohshita, K. Takaki, Angew. Chem. Int. Ed.; 2012, 51, 235.
Crystal data for compound Zꢀ2j: C15H20BBrO2; MW = 323.03,
Monoclinic space group P2(1)/c, final R indices [I > 2σ(I)], R1 =
0.0369, wR2 = 0.0892, R indices (all data) R1 = 0.0563, wR2 =
0.0990, a = 10.0397(8) Å, b = 7.5575(6) Å, c = 20.5113(15) Å, α =
90o, β = 97o, γ = 90o, V = 1544.3(2) Å3, T = 296(2) K, Z = 4,
reflections collected/unique 14022/2704 (Rint = 0.0305), number of
observations [> 2σ(I)] 1988, parameters: 172. Supplementary
crystallographic data have been deposited at the Cambridge
Crystallographic Data Center. CCDC.
1
2
3
4
OH (1u)d
OBn (1v)
OAc (1w)
NHTs (1x)
76 (Z-2v)
72 (Z-2w)
87 (Z-2x)
> 99:1
a
Reaction conditions: 0.5 mmol of substrate, 0.6 mmol of
bis(pinacolato)diboron, 5 mol% CuCl, 6 mol% P(C6H4OMeꢀp)3, 20
b
mol% K2CO3 and 1.0 mmol of iꢀPrOH in 2 mL of Et2O at rt.
Determined by 1H NMR from the crude mixture. Isolated yield.
c
d
6
Reaction carried out in the absence of MeOH.
5
To further show the practicality and efficiency of this
catalytic system, the reaction of 1ꢀphenylꢀ1ꢀpropyne 1a has
been conducted on a 20 gꢀscale, showing high efficiency and
practicality (eq 2).
7
8
9
10
In summary, we have developed an efficient and practical
protocol to synthesize stereodefined alkenylboronates from
internal alkynes in good yields with excellent regioꢀ and
stereoselectivity. This convenient procedure applying the
readily available ligand (P(C6H4OMeꢀp)3) and base (K2CO3)
15 may show its potential in organic synthesis. The electronꢀrich
P(C6H4OMeꢀp)3 has increased the catalytic activity of CuCl
greatly by pumping more electrons to the metal center.
Further studies in this area is being carried out in this
laboratory.
10 Crystal data for compound Zꢀ2s: C19H29BO2; MW
= 300.23,
Monoclinic space group P2(1)/c, final R indices [I > 2σ(I)], R1 =
0.0494, wR2 = 0.1186, R indices (all data) R1 = 0.0651, wR2 =
0.1302, a = 12.1475(11) Å, b = 6.0763(6) Å, c = 24.653(2) Å, α =
90o, β = 90o, γ = 90o, V = 1819.6(3) Å3, T = 173(2) K, Z = 4,
reflections collected/unique 19852/3210 (Rint = 0.0441), number of
observations [> 2σ(I)] 2549, parameters: 199. Supplementary
crystallographic data have been deposited at the Cambridge
Crystallographic Data Center. CCDC.
20
We thank the National Basic Research Program of China (No.
2011CB808700) and National Natural Science Foundation of
China for financial support.
Notes and references
25 a Shanghai Key Laboratory of Green Chemistry and Chemical Process,
Department of Chemistry, East China Normal University, 3663 North
Zhongshan Lu, Shanghai 200062, P. R. China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu,
30 Shanghai 200032, P. R. China
Fax: (+86)21ꢀ64167510 Eꢀmail: masm@sioc.ac.cn
† Electronic Supplementary Information (ESI) available: [experimental
procedures, NMR spectra. For ESI and other electronic format see
DOI: 10.1039/b000000x/
35
1
For reviews, see: (a) D. S. Matteson, Chem. Rev.; 1989, 89, 1535; (b)
D. S. Matteson, Acc. Chem. Res.; 1988, 21, 294; (c) I. Beletskaya, C.
Moberg, Chem. Rev.; 2006, 106, 2320; (d) G. J. Irvine, G. Lesley, T.
B. Marder, N. C. Norman, C. R. Rice, E. G. Robins, W. R. Roper, G.
R. Whittell, L. J. Wright, Chem. Rev.; 1998, 98, 2685.
40
2
For reviews, see: (a) N. Miyaura, A. Suzuki, Chem. Rev.; 1995, 95,
2457; (b) A. Suzuki, J. Organomet. Chem.; 1999, 576, 147.
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