Dialkynylation of aryl aldehydes using dialkynylboron chlorides: A transition-metal-free route to 1,4-diynes

Article abstract of DOI:10.1016/j.jorganchem.2012.09.008

Dialkynylboron chlorides couple smoothly with aryl aldehydes at room temperature to afford 1,4-dialkynes in good to excellent yields. Dialkynylboron halides act simultaneously as Lewis acid and reactant in this coupling reaction.

Full text of DOI:10.1016/j.jorganchem.2012.09.008

Journal of Organometallic Chemistry 721-722 (2012) 164e166
Contents lists available at SciVerse ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Dialkynylation of aryl aldehydes using dialkynylboron chlorides: A transition-
metal-free route to 1,4-diynes
Min-Liang Yao b, Adam B. Pippin a, Zhong-Zhi Wu a, Michael P. Quinn a, Li Yong a, Marepally S. Reddy b,
,b,
George W. Kabalka a
*
a Department of Chemistry, The University of Tennessee, Knoxville, Tennessee 37996-1600, United States
b Department of Radiology, The University of Tennessee, Knoxville, Tennessee 37996-1600, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Dialkynylboron chlorides couple smoothly with aryl aldehydes at room temperature to afford
1,4-dialkynes in good to excellent yields. Dialkynylboron halides act simultaneously as Lewis acid and
reactant in this coupling reaction.
Received 6 July 2012
Received in revised form
13 September 2012
Ó 2012 Elsevier B.V. All rights reserved.
Accepted 14 September 2012
Keywords:
Diyne
Aldehyde
Alkynylboron
Boron halide
Alkynylation
1. Introduction
applications in the syntheses of complex organic molecules. Finally,
the reaction work-up can be tedious if stoichiometric quantities of
1,4-Diynes are valuable building blocks for the construction of
carbon networks due to their high carbon content [1e3]. In addi-
tion, 1,4-diynes are useful intermediates in the preparation of
pyrroles [4e6] and furans [6] as well as skipped dienes [7,8]. In fact,
a large number of polyunsaturated fatty acids have been synthe-
sized from 1,4-diynes through a catalytic Lindar partial reduction
reaction [9]. The generally used approach to 1,4-diynes [10]
involves the cross-coupling of propargylic electrophiles with
copper-acetylides [11,12]. The requisite acetylenic copper species
are usually generated in situ from combinative systems, such as
alkynylmetals/copper (I) salts [13e16], terminal acetylene/base/
copper (I) salts [6,17e21], and TMS-protected acetylene/fluoride
source/copper (I) salts [22]. Although widely employed, these
copper-mediated cross-coupling reactions suffer from several
limitations. First, the basic reaction conditions sometimes induce
the isomerization of the product 1,4-diyne to form an difficult-to-
separate alkynylallene [23]. Second, functional group incompati-
bility caused by highly nucleophilic alkynylmetals restricts their
copper salt are used. In addition to the copper-mediated cross-
coupling reactions, some scattered examples of Lewis acid medi-
ated coupling of soft nucleophiles (alkynylalane [24,25] and alky-
nylsilane [25,26]) with propargylic electrophiles have been
reported.
Recently we discovered a novel transition-metal-free route to
1,4-diynes via the coupling of propargyl alkoxides with alky-
nylboron dichlorides [27] (Scheme 1). Herein, we report a novel
route to 1,4-diynes via dialkynylation of aryl aldehydes using dia-
lkynylboron chlorides.
2. Results and discussion
The difunctionalization of aryl aldehydes using dual-reagent
catalyst systems has drawn considerable attention in recent years
[28e31]. Our research group has been investigating boron halide
chemistry for many years [32]; during this time we have discovered
that, in the absence of transition-metal catalysts, certain boron
halide derivatives are powerful reagents for use in difunctionali-
zation of aryl aldehydes. For example, we have reported the diha-
logenation [33], chloroalkylation [34,35], dialkenylation [36,37],
and haloallylation [38,39] of aryl aldehydes under very mild reac-
tion conditions.
* Corresponding author. Department of Chemistry, The University of Tennessee,
Knoxville, Tennessee 37996-1600, United States, Tel.: þ1 865 9742997.
E-mail address: kabalka@utk.edu (G.W. Kabalka).
0022-328X/$ e see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2012.09.008

M.-L. Yao et al. / Journal of Organometallic Chemistry 721-722 (2012) 164e166
165
4. Experimental
Previous work:
R
R
+
Cl2B
R2
All glassware was dried in an oven at 120 ꢀC and flushed
with dry argon. All reactions were carried out under an argon
atmosphere. Dichloromethane (DCM) was distilled from CaH2.
Other reagents were purchased from commercial sources and used
as received. Products were purified by flash chromatography using
silica gel (60 Å, 230e400 mesh). 1H NMR and 13C NMR were
obtained utilizing a Bruker 250 MHz or a Bruker 400 MHz (proton)
multinuclear analytical NMR. Chemical shifts for 1H NMR and 13C
NMR spectra were referenced to TMS and measured with respect to
the residual protons in the deuterated solvents.
OLi
R1
R1
R2
Ar
Cl
B
Current work:
+
R
ArCHO
R
R
R
Scheme 1.
Alkynylboranes are known to add to nonconjugated aldehydes
and more slowly to ketones to give the corresponding propargyl
alcohols [40e42]. However, to the best of our knowledge, the
reaction of dialkynylboron halides with aldehydes has never been
explored. Encouraged by the dialkenylation of aryl aldehydes using
dialkenylboron halide [37], we decided to examine the reaction of
dialkynylboron halides and aldehydes. The required dialkynylboron
chloride is readily synthesized by first deprotonating a terminal
alkyne (2.0 eq.) with butyllithium followed by addition of one
equivalent of BCl3. The resulting dialkynylboron chloride is used
directly without further purification. The results indicate that the
reaction of dialkynylboron chlorides with aldehydes proceeds
smoothly at room temperature to generate the desired 1,4-diynes
in good to excellent yields. As shown in Table 1, functional
groups, such as eBr, eCl, eOMe and eNO2, are unaffected under the
reaction conditions. This method is notable for its simplicity and
mildness.
4.1. Typical procedure for the dialkynylation reaction
Phenylacetylene (306 mg, 3.0 mmol), along with 10 mL of dry
hexanes, was placed in a dry, argon-flushed, 50 mL round-
bottomed flask equipped with a stirring bar. The solution was
cooled using an ice bath and n-butyllithium (3.2 mmol, 2 mL of
1.6 mmol hexane solution) was added via syringe. The ice bath was
removed and the solution allowed to stir for 20 min at room
temperature. The solution was then cooled in an ice bath and boron
trichloride (1.6 mmol, 1.6 mL of 1.0 M hexane solution) was added
via syringe. The ice bath was removed and the solution allowed to
stir for 20 min at room temperature. The solution was again cooled
using an ice bath and benzaldehyde (159 mg, 1. 5 mmol in 2 mL of
dry dichloromethane) was added. The ice bath was removed and
the solution allowed to stir at room temperature until completion
(monitored by TLC). Water was added to quench the reaction and
the reaction mixture was extracted with hexanes (3 ꢁ 10 mL). The
combined organic solvent was dried over anhydrous MgSO4,
filtered, and filtrate concentrated under reduced pressure. The
product was purified by silica gel column chromatography [elute:
hexane e ethyl acetate]. The 1H NMR and 13C NMR spectra of
known compounds 3a [30], 3b [27], 3c [30], 3d [31], 3f [31], 3g [30],
3k [30] are consistent with literature values.
Based on our previous achievements in coupling of alkoxides
with stereodefined halovinylboron dihalides [43e45] and alky-
nylboron dihalides [27], we believe that this dialkynylation reaction
begins with a Grignard-like addition of dialkynylboron chloride to
generate propargyloxoboron intermediate 2, followed by a rear-
rangement to afford the product 1,4-diyne (Scheme 2).
4.2. 1,5-Diphenyl-3-(2-fluorophenyl)-1,4-pentadiyne (3e)
3. Conclusion
NMR (250 MHz, CDCl3):
7.09e7.49 (m, 12 H), 6.80 (d, J ¼ 8.0 Hz, 1 H), 5.94 (s, 2H), 5.10 (s,
1H). 13C NMR (62.5 MHz, CDCl3):
161.8, 157.9, 131.8, 129.7, 129.5,
129.3, 129.2, 128.3, 128.2, 127.3, 126.6, 126.4, 125.6, 125.4, 125.4,
124.5, 122.8, 119.0, 115.7, 115.4, 85.5, 82.3, 23.9. HRMS for C23H15F:
310.1158. Found: 310.1166.
d 7.07e7.82 (m, 14 H), 5.42 (s, 1H).
In summary, a novel dialkynylation reaction of aryl aldehydes in
the absence of transition metal catalysts has been developed using
readily available dialkynylboron chlorides. The new method
provides an efficient route to symmetric 1,4-diynes. This study also
extends the knowledge-base related to carbonyl addition chemistry
and complements the well documented 1,2-addition reactions of
aldehydes with organometallic reagents (RMgX, RZnX, and 9-BBN
derivatives) [46e48].
d
d
4.3. 1,5-Diphenyl-3-(benzo[d][3,4]dioxole)-1,4-pentadiyne (3h)
NMR (250 MHz, CDCl3):
d
7.09e7.49 (m, 12H), 6.80 (d, J ¼ 8.0 Hz,
147.9,
1H), 5.94 (s, 2H), 5.10 (s, 1H). 13C NMR (62.5 MHz, CDCl3):
d
Table 1
147.0, 131.8, 128.2, 122.9, 120.5, 108.2, 108.0, 101.2, 86.6, 82.7, 29.8.
HRMS for C24H16O2: 336.1150. Found: 336.1162.
Dialkynylation of aryl aldehyde using dialkynylboron chloridea.
Entry
Ar
R
Product
Yield (%)b
1
2
3
4
5
6
7
8
Ph
4-MePh
4-BrPh
4-ClPh
2-FPh
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
n-C4H9
3a
3b
3c
3d
3e
3f
3g
3h
3i
76
87
67
85
82
90
75
63
53
42
50
25
4.4. 1,5-Diphenyl-3-(3-methoxyphenyl)-1,4-pentadiyne (3i)
NMR (250 MHz, CDCl3):
4 H), 7.22e7.32 (m, 7 H), 6.39e7.02 (m, 2 H), 5.51 (s, 1 H), 3.89 (s,
3 H). 13C NMR (62.5 MHz, CDCl3):
156.1, 131.8, 128.8, 128.6, 128.0,
d
7.81 (d, J ¼ 7.7 Hz, 1 H), 7.44e7.46 (m,
4-FPh
d
2-MePh
3,4-(OCH2O)Ph
3-MeOPh
4-NO2Ph
2-Naphthyl
4-ClPh
123.2, 120.9, 110.9, 87.2, 81.3, 55.8, 24.0. HRMS for C24H18O:
322.1358. Found: 322.1369.
9
10
11
12
3j
3k
3l
4.5. 1,5-Di(n-butyl)-3-(4-chlorophenyl)-1,4-pentadiyne (3l)
a
NMR (400 MHz, CDCl3):
d
7.24e7.32 (m, 4 H), 6.37 (s, 1H), 5.10 (s,
147.9, 147.0, 131.8, 128.2, 122.9,
Reactions run on a 1.5 mmol scale at room temperature.
Isolated yield based on benzaldehyde.
1H). 13C NMR (100 MHz, CDCl3):
d
b

166
M.-L. Yao et al. / Journal of Organometallic Chemistry 721-722 (2012) 164e166
Ar
R
O
Cl
B
R
B
1. BuLi
2. BCl
ArCHO
Cl
2 R
Ar
3
R
R
R
2
R
3
alkoxide intermediate
Scheme 2.
[22] F. Montel, R. Beaudegnies, J. Kessabi, B. Martin, E. Muller, S. Wendeborn,
P.M. Jung, J. Org. Lett. 8 (2006) 1905e1908.
[23] N.L. Hungerford, W. Kitching, J. Chem. Soc. Perkin Trans. 1 (1998) 1839e1859.
[24] M. Yoshimastu, H. Shimizu, T. Kataoka, J. Chem. Soc. Chem. Commun. (1995)
149e150.
120.5, 108.2, 108.0, 101.2, 86.6, 82.7, 29.8. HRMS for C19H23Cl:
286.1488. Found: 286.1503.
Acknowledgment
[25] J. Kessabi, R. Beaudegnies, P.M.J. Jung, B. Martin, F. Montel, S. Wendeborn, Org.
Lett. 8 (2006) 5629e5632;
L.T. Scott, G.J. DeCicco, J.L. Hyun, G. Reinhardt, J. Am. Chem. Soc. 107 (1985)
6546e6555.
[26] J.S. Yadav, B.V.S. Reddy, N. Thrimurtulu, N.M. Reddy, A.R. Prasad, Tetrahedron
Lett. 49 (2008) 2031e2033.
Financial support from the U. S. Department of Energy, the
Petroleum Research Fund, and the Robert H. Cole Foundation is
gratefully acknowledged.
[27] G.W. Kabalka, M.-L. Yao, S. Borella, Org. Lett. 8 (2006) 879e881.
[28] S. Podder, J. Choudhury, U.K. Roy, S. Roy, J. Org. Chem. 72 (2007) 3100e3103.
[29] Y. Fu, J.-X. Wang, K. Wang, Y. Hu, Tetrahedron 64 (2008) 11124e11128.
[30] Y. Kuninobu, E. Ishii, K. Takai, Angew. Chem. Int. Ed. 46 (2007) 3296e3299.
[31] C.A. Camois, J.B. Gianino, D.M. Pinkerton, B.L. Ashfeld, Org. Lett. 13 (2011)
5680e5683.
[32] M.-L. Yao, G.W. Kabalka, Organic synthesis using boron and organoboron
halides, in: N. Hosmane (Ed.), Boron Science: New Technologies & Applica-
tions, CRC Press, 2012, pp. 559e601.
[33] G.W. Kabalka, Z. Wu, Tetrahedron Lett. 41 (2000) 579e581.
[34] G.W. Kabalka, Z. Wu, Y. Ju, Tetrahedron Lett. 42 (2001) 6239e6241.
[35] G.W. Kabalka, Z. Wu, Y. Ju, M.-L. Yao, J. Org. Chem. 70 (2005) 10285e10291.
[36] G.W. Kabalka, Z. Wu, Y. Ju, Org. Lett. 4 (2002) 1491e1493.
[37] G.W. Kabalka, M.-L. Yao, S. Borella, Z. Wu, Y. Ju, T. Quick, J. Org. Chem. 73
(2008) 2668e2673.
[38] M.-L. Yao, S. Borella, T. Quick, G.W. Kabalka, J. Chem. Soc. Dalton (2008) 776e778.
[39] M.P. Quinn, M.-L. Yao, L. Yong, G.W. Kabalka, Synthesis (2011) 3815e3820.
[40] H.C. Brown, G.A. Molander, S.M. Singh, U.S. Racherla, J. Org. Chem. 50 (1985)
1577e1582.
[41] J.C. Evans, C.T. Goralski, D.L. Hasha, J. Org. Chem. 57 (1992) 2941e2943.
[42] E.J. Corey, K.A. Cimprich, J. Am. Chem. Soc. 116 (1994) 3151e3152.
[43] G.W. Kabalka, M.-L. Yao, S. Borella, Z. Wu, Chem. Commun. (2005) 2492e2494.
[44] G.W. Kabalka, M.-L. Yao, S. Borella, Z. Wu, Org. Lett. 7 (2005) 2865e2867.
[45] G.W. Kabalka, Z. Wu, Y. Ju, Org. Lett. 6 (2004) 3929e3931.
[46] P. Jacob, H.C. Brown, J. Org. Chem. 42 (1977) 579e580.
[47] H.C. Brown, R.S. Randad, K.S. Bhat, M. Zaidlewicz, U.S. Racherla, J. Am. Chem.
Soc. 112 (1990) 2389e2392.
References
[1] Review U.H.F. Bunz, Angew. Chem. Int. Ed. 33 (1994) 1073e1076.
[2] Review E.L. Spitler, C.A. Johnson, M.M. Haley, Chem. Rev. 106 (2006) 5344e5386.
[3] R. Amemiya, K. Suwa, J. Toriyama, Y. Nishimura, M. Yamaguchi, J. Am. Chem.
Soc. 127 (2005) 8252e8253.
[4] B.Ramanathan, A.J.Keith, D.Armstrong,A.L. Odom, Org. Lett.6(2004)2957e2960.
[5] S. López-Tosco, D. Tejedor, J. González-Platas, F. García-Tellado, Chem. Eur. J.
(2011) 6847e6850 (and references cited therein).
[6] T. Wang, X.-L. Chen, L. Chen, Z.-p. Zhan, Org. Lett. 13 (2011) 3324e3327.
[7] T. Chakraborty, P. Laxman, Tetrahedron Lett. 44 (2003) 4989e4992.
[8] G. Saha, M.K. Basu, S. Kim, Y.-J. Jung, Tetrahedron Lett. 40 (1999) 7179e7183.
[9] S. Durand, J.-L. Parrain, M. Santelli, J. Chem, Soc. Perkin Trans. 1 (2000) 253e273.
[10] Review C. Tedeschi, C. Saccavini, L. Maurette, M. Soleihavoup, R. Chauvin,
J. Organomet. Chem. 670 (2003) 151e169.
[11] Review K.M. Nicholas, Acc. Chem. Res. 20 (1987) 207e214.
[12] Review T.J.J. Müller, Eur. J. Org. Chem. (2001) 2021e2033.
[13] M.R. Gronquist, J. Meinwald, J. Org. Chem. 66 (2001) 1075e1081.
[14] M. Sanniere, Y. Le Merrer, B. Barbe, T. Koscielniak, J. Dumas, et al., Angew.
Chem. Int. Ed. Eng. 28 (1989) 614e617.
[15] P. Dussault, I.Q. Lee, J. Org. Chem. 60 (1995) 218e226.
[16] D. Mesnard, L. Miginiac, J. Organomet. Chem. 373 (1989) 1e10.
[17] A. Sevin, W. Chodkiewicz, P. Cadiot, Bull. Soc. Chim. Fr. 5-6 (1974) 913e917.
[18] T. Jeffery, S. Gueugnot, G. Linstrumelle, Tetrahedron Lett. 33 (1992) 5757e5760.
[19] K.K. Pivinistky, M.A. Lapitskaya, L.L. Vasiljeva, Synthesis (1993) 65e66.
[20] S. Durand, J. Parrain, M. Santelli, Synthesis (1998) 1015e1018.
[21] T. Caruso, A. Spinella, Tetrahedron 59 (2003) 7787e7790.
[48] C.H. Burgos, E. Canales, K. Matos, J.A. Soderquist, J. Am. Chem. Soc. 127 (2005)
8044e8049.