Copper-catalyzed three-component carboboration of alkynes and alkenes

Article abstract of DOI:10.1021/ol4001526

Carboboration of alkynes was found to take place efficiently by a three-component coupling reaction with diboron and carbon electrophiles under copper catalysis to afford diverse multisubstituted borylalkenes in a stereoselective manner. The carboboration was also applicable to alkenes, leading to the formation of multisubstituted borylalkanes via regioselective carbon-boron and carbon-carbon bond-forming processes.

Full text of DOI:10.1021/ol4001526

ORGANIC
LETTERS
2013
Vol. 15, No. 4
952–955
Copper-Catalyzed Three-Component
Carboboration of Alkynes and Alkenes
Hiroto Yoshida,* Ikuo Kageyuki, and Ken Takaki
Department of Applied Chemistry, Graduate School of Engineering,
Hiroshima University, Higashi-Hiroshima 739-8527, Japan
yhiroto@hiroshima-u.ac.jp
Received January 17, 2013
ABSTRACT
Carboboration of alkynes was found to take place efficiently by a three-component coupling reaction with diboron and carbon electrophiles under
copper catalysis to afford diverse multisubstituted borylalkenes in a stereoselective manner. The carboboration was also applicable to alkenes,
leading to the formation of multisubstituted borylalkanes via regioselective carbonꢀboron and carbonꢀcarbon bond-forming processes.
Inviewofthehighsyntheticsignificanceoforganoboron
compounds,1 which can be utilized especially for carbonꢀ
carbon bond-forming processes through SuzukiꢀMiyaura
coupling,2 the Petasis reaction,3 transition metal-catalyzed
conjugate addition,4 etc., the development of new synthetic
routes to hitherto unprecedented classes of organoboron
compounds is of great importance. Recently, much atten-
tion has been paid to copper-catalyzed borylation reactions
of unsaturated carbon linkages, in which nucleophilic
borylcopper species derived from copper(I) complexes
and diborons serve as key intermediates.5,6 In these
transformations, the borylcopper species add across the
unsaturated CꢀC bonds to give β-borylorganocopper
species, which are convertible into final products via proto-
nation, β-oxygen elimination, cyclization, etc. We have just
reported copper-catalyzed diborylation7a and borylstanny-
lation7b of alkynes through capture of the β-borylalkenyl
copper species with a boron (diboron) or a tin electrophile
(tin alkoxide) and, thus, envisaged that the use of a suitable
carbon electrophile for trapping the β-borylalkenyl copper
species would lead to a carboboration reaction, in which a
BꢀC and a CꢀC bond are formed all in one pot (Scheme 1).
Although pioneering work by Suginome demonstrated
that the nickel- and palladium-catalyzed carboboration of
(1) Boronic Acids; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2011.
(2) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Miyaura, N. Top. Curr. Chem. 2002, 219, 11.
(3) (a) Petasis, N. A.; Goodman, A.; Zavialov, I. A. Tetrahedron
€
1997, 53, 16463. (b) Koolmeister, T.; Sodergren, M.; Scobie, M. Tetra-
hedron Lett. 2002, 43, 5965.
(4) (a) Hayashi, T. Synlett 2001, 879. (b) Hayashi, T.; Yamazaki, K.
Chem. Rev. 2003, 103, 2829.
(5) For examples, see: (a) Ito, H.; Yamanaka, H.; Tateiwa, J.;
Hosomi, A. Tetrahedron Lett. 2000, 41, 6821. (b) Takahashi, K.;
Ishiyama, T.; Miyaura, N. J. Organomet. Chem. 2001, 625, 47. (c) Ito,
H.; Ito, S.; Sasaki, Y.; Matsuura, K.; Sawamura, M. J. Am. Chem. Soc.
2007, 129, 14856. (d) Ito, H.; Sasaki, Y.; Sawamura, M. J. Am. Chem.
Soc. 2008, 130, 15774. (e) Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed. 2008,
47, 145. (f) Ito, H.; Kosaka, Y.; Nonoyama, K.; Sasaki, Y.; Sawamura,
M. Angew. Chem., Int. Ed. 2008, 47, 7424. (g) Lee, J.-E.; Kwon, J.; Yun,
J. Chem. Commun. 2008, 733. (h) Lee, Y.; Hoveyda, A. H. J. Am. Chem.
Soc. 2009, 131, 3160. (i) Lee, Y.; Jang, H.; Hoveyda, A. H. J. Am. Chem.
Soc. 2009, 131, 18234. (j) Lillo, V.; Prieto, A.; Bonet, A.; Dıaz-Requejo,
€
(6) For studies on borylcopper species, see: (a) Laitar, D. S.; Muller,
ꢀ
ꢀ
M. M.; Ramırez, J.; Perez, P. J.; Fernandez, E. Organometallics 2009, 28,
659. (k) Kim, H.-R.; Jung, I.-G.; Yoo, K.; Jang, K.; Lee, E.-S.; Yun, J.;
Son, S.-U. Chem. Commun. 2010, 46, 758. (l) Sasaki, Y.; Zhong, C.;
Sawamura, M.; Ito, H. J. Am. Chem. Soc. 2010, 132, 1226. (m) Ito, H.;
Toyoda, T.; Sawamura, M. J. Am. Chem. Soc. 2010, 132, 5990.
(n) Zhong, C.; Kunii, S.; Kosaka, Y.; Sawamura, M.; Ito, H. J. Am.
Chem. Soc. 2010, 132, 11440. (o) Kim, H.-R.; Yun, J. Chem. Commun.
2011, 47, 2943. (p) Sasaki, Y.; Horita, Y.; Zhong, C.; Sawamura, M.; Ito,
H. Angew. Chem., Int. Ed. 2011, 50, 2778. (q) Jang, H.; Zhugralin, A. R.;
Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133, 7859.
(r) Kobayashi, S.; Xu, P.; Endo, T.; Ueno, M.; Kitanosono, T. Angew.
Chem., Int. Ed. 2012, 51, 12763. (s) Thorpe, S. B.; Calderone, J. A.;
Santos, W. L. Org. Lett. 2012, 14, 1918.
P.; Sadighi, J. P. J. Am. Chem. Soc. 2005, 127, 17196. (b) Segawa, Y.;
Yamashita, M.; Nozaki, K. Angew. Chem., Int. Ed. 2007, 46, 6710.
(7) (a) Yoshida, H.; Kawashima, S.; Takemoto, Y.; Okada, K.; Ohshita,
J.; Takaki, K. Angew. Chem., Int. Ed. 2012, 51, 235. (b) Takemoto, Y.;
Yoshida, H.; Takaki, K. Chem.;Eur. J. 2012, 18, 14841.
(8) (a) Suginome, M.; Yamamoto, A.; Murakami, M. J. Am. Chem.
Soc. 2003, 125, 6358. (b) Suginome, M.; Yamamoto, A.; Murakami, M.
Angew. Chem., Int. Ed. 2005, 44, 2380. (c) Suginome, M.; Yamamoto,
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metallics 2006, 25, 2911.
r
10.1021/ol4001526
Published on Web 02/05/2013
2013 American Chemical Society

The carboboration was also applicable to variously
substituted diarylalkynes (1bꢀ1e) to give the respective
products (4baꢀ4ea) in moderate to good yields (Table 2,
entries 1ꢀ4), and it should benotedthatthe arylꢀBr bonds
in 4da and 40da totally remained intact,14 demonstrating
the high functional group compatibility of the carboboration.
The exclusive formation of a single regioisomer (4fa and
4ga), whose benzyl moiety was attached to the geminal
position of the phenyl moiety, was observed in the reaction
of alkyl(aryl)alkynes (1f and 1g) (entries 5 and 6),15 and
furthermore dialkylalkynes (1h and 1i) could participate in
the reaction to furnish the products (entries 7 and 8). The
reaction of phenylacetylene (1j) proceeded with perfect
regioselectivity to afford 4ja bearing the benzyl moiety at
the more substituted site (entry 9), and such terminal
aliphaticalkynesas1-octyne (1k) and cyclopentylacetylene
(1l) were also convertible into the carboboration products
(entries 10 and 11), being in marked contrast to the results
recently reported by Tortosa.11
Scheme 1. Copper-Catalyzed Borylations of Alkynes
alkynes occurred via direct activation of a BꢀC bond8 or
three-component coupling with a boron electrophile (boron
chloride) and a carbon nucleophile (organometallic com-
pound),9 the search for carboboration of other modes10 is
highly desirable. We report herein the copper-catalyzed
three-component carboboration of alkynes and alkenes, in
which a boron nucleophile and a carbon electrophile are
installed into CꢀC multiple bonds. The closely related
copper-catalyzed carboboration11 and boracarboxylation12
of alkynes have been recently reported.
Table 2. Carboboration of Alkynes with Benzyl Chloridea
First we conducted the reaction of diphenylacetyl-
ene (1a) with bis(pinacolato)diboron ((pin)BꢀB(pin)) (2)
and benzyl chloride (3a) in toluene in the presence of
13
Cu(OAc)2ꢀPCy3 and KOtBu and observed that BꢀC
and CꢀC bonds were constructed in one pot to afford a
carboboration product in 45% yield as a mixture of two
stereoisomers (4aa:40aa = 87:13) (entry 1, Table 1). The use
of such polar solvents as acetonitrile, DMF, and DMI was
found to improve the yield and the stereoselectivity signifi-
cantly (entries 2ꢀ4), whereas the reaction in THF only gave
unsatisfactory results (entry 5).
time yield ratio
entry
R
R0
(h) (%)b 4:40
4
1
4-MeOC6H4 4-MeOC6H4 (1b) 54 67
ꢀ
4ba
2
Ph
Ph
Ph
Me
Et
nPr
Me
H
4-MeOC6H4 (1c) 29 84
52:48 4ca, 40ca
51:49 4da, 40da
55:45 4ea, 40ea
>99:1 4fa
3
4-BrC6H4 (1d)
2-Thienyl (1e)
Ph (1f)
27 58
27 49
24 54
15 50
24 57
Table 1. Solvent Effect on Cu-Catalyzed Carboborationa
4
5
6
Ph (1g)
>99:1 4ga
7
nPr (1h)
ꢀ
4ha
8
nPent (1i)
Ph (1j)
8
46
80:20 4ia, 40ia
9
46 44
32 51
52 48
>99:1 4ja
10
11
H
nHex (1k)
Cyclopent (1l)
56:44 4ka, 40ka
55:45 4la, 40la
H
a General procedure: 1 (0.30 mmol), 2 (0.39 mmol), 3a (0.90 mmol),
KOtBu (0.45 mmol), Cu(OAc)2 (6.0 μmol), PCy3 (0.021 mmol), DMF
(0.55 mL). b Yield of isolated 4 and 40.
entry
solvent
toluene
time (h)
yield (%)b
4aa:40aa
1
2
3
4
5
27
30
29
33
28
45
63
67
56
38c
87:13
94:6
(10) (a) Mikhaikov, B. M.; Bubnov, Y. N. Tetrahedron Lett. 1971,
2127. (b) Bubnov, Y. N.; Nesmeyanova, O. A.; Rudashevskaya, T. Y.;
Mikhaikov, B. M.; Kazansky, B. A. Tetrahedron Lett. 1971, 2153.
acetonitrile
DMF
>99:1
>99:1
78:22
DMI
€
(c) Wrackmeyer, B.; Noth, H. J. Organomet. Chem. 1976, 108, C21.
THF
(d) Okuno, Y.; Yamashita, M.; Nozaki, K. Angew. Chem., Int. Ed. 2011,
50, 920.
a General procedure: 1a (0.30 mmol), 2 (0.39 mmol), 3a (0.90 mmol),
KOtBu (0.45 mmol), Cu(OAc)2 (6.0 μmol), PCy3 (0.021 mmol), solvent
(0.55 mL). b Yield of isolated 4aa and 40aa. c NMR yield.
(11) A part of this work was presented at the 59th symposium on
organometallic chemistry, Japan on September 15, 2012 (No. P3B-04).
For copperꢀxantphos-catalyzed carboboration of alkynes, see: Alfaro,
ꢀ
R.; Parra, A.; Alemean, J.; G. Ruano, J. L.; Tortosa, M. J. Am. Chem.
Soc. 2012, 134, 15165.
(12) Zhang, L.; Cheng, J.; Carry, B.; Hou, Z. J. Am. Chem. Soc. 2012,
134, 14314.
(13) Copper(II) acetate would be reduced to a copper(I) complex in
situ. See: Hammond, B.; Jardine, F. H.; Vohra, A. G. J. Inorg. Nucl.
Chem 1971, 33, 1017.
(9) (a) Yamamoto, A.; Suginome, M. J. Am. Chem. Soc. 2005, 127,
15706. (b) Daini, M.; Yamamoto, A.; Suginome, M. J. Am. Chem. Soc.
2008, 130, 2918. (c) Daini, M.; Suginome, M. Chem. Commun. 2008,
5224.
Org. Lett., Vol. 15, No. 4, 2013
953

at the γ-position solely (entry 8).16 Besides, simple alkyl
(pseudo)halides (3j and 3k) were transformable into the
carboboration products (4aj and 4ak) (entries 9 and 10),
and the formation of the cyclopropylmethylated product
(4al) in the reaction using cyclopropylmethyl bromide (3l)
suggests that a radical pathway is not operative in the
carboboration (entry 11). The reaction was also applicable
to 1,5-dibromopentane (3m), one of whose CꢀBr bonds
was converted into the CꢀC bond (entry 12).
Table 3. Carboboration of Diphenylacetylene with Various
Carbon Electrophilesa
The versatility of the copper catalysis was demon-
strated by the success in the carboboration of alkenes
(Scheme 2).17,18 Thus, treatment of dimethylphenylvinyl-
silane (5a) with 2 and 3a in the presence of SIMesCuCl
resulted in the exclusive formation of 6aa in 85% yield, and
moreover the reaction of vinylborane (5b) or styrene (5c)
also smoothly proceeded with a regioselectivity similar to
that with the vinylsilane, giving the carboboration pro-
ducts (6ba and 6ca) in 68% or 65% yield, respectively.19
Scheme 2. Carboboration of Alkenes with Benzyl Chloride
a General procedure: 1a (0.30 mmol), 2 (0.39 mmol), 3 (0.90 mmol),
KOtBu (0.45 mmol), Cu(OAc)2 (6.0 μmol), PCy3 (0.021 mmol), DMF
(0.55 mL). b Yield of isolated 4.
As depicted in Scheme 3, formation of borylcopper
species 7 from a CuꢀOR (R = Ac or tBu) complex with
2 triggers the carboboration. Subsequent insertion of an
alkyne (or an alkene) into the CuꢀB bond of 7 (step A),
followed by capture of the resulting β-borylalkenyl (or
alkyl) copper species 8 with a carbon electrophile, provides
a carboboration product and a copper tert-butoxide (step B),
The broad substrate scope on carbon electrophiles was
exemplified by use of substituted benzyl chlorides: treat-
ment of 2,4,6-trimethylbenzyl chloride (3b) or 2,4,6-triiso-
propylbenzyl chloride (3c) with 1a and 2 produced good
yields of the respectiveproducts(4ab and 4ac), despite their
considerable steric congestion (Table 3, entries 1 and 2).
The reaction of para-substituted (3dꢀ3g) or ortho-substi-
tuted (3h) benzyl chlorides also took place facilely (entries
3ꢀ7), and a cinnnamyl moiety could be installed into the
CꢀC triple bond by employing cinnamyl phosphate (3i) as
a carbon electrophile, where the substitution occurred
Scheme 3. A Plausible Catalytic Cycle for Carboboration
(14) For copper-catalyzed borylation of ArꢀBr bonds, see: Kleeberg,
C.; Dang, L.; Lin, Z.; Marder, T. B. Angew. Chem., Int. Ed. 2009, 48,
5350.
(15) The reaction of 1f, 2, and 3a under Tortosa’s conditions pro-
duced a mixture of regioisomers in contrast to the result described
herein. See ref 11.
(16) For copper-catalyzed SN20 selective substitution of allylic elec-
trophiles, see: (a) Ito, H.; Kawakami, C.; Sawamura, M. J. Am. Chem.
Soc. 2005, 127, 16034. (b) Whittaker, A. M.; Rucker, R. P.; Lalic, G.
Org. Lett. 2010, 12, 3216. (c) Ohmiya, H.; Yokokawa, N.; Sawamura, M.
Org. Lett. 2010, 12, 2438. (d) Ohmiya, H.; Yokobori, U.; Makida, Y.;
Sawamura, M. J. Am. Chem. Soc. 2010, 132, 2895. (e) Ito, H.; Okura, T.;
Matsuura, K.; Sawamura, M. Angew. Chem., Int. Ed. 2010, 49, 560.
(f) Guzman-Martinez, A.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132,
10634. (g) Tortosa, M. Angew. Chem., Int. Ed. 2011, 50, 3950. (h) Park,
J. K.; McQuade, D. T. Angew. Chem., Int. Ed. 2012, 51, 2717. See also
ref 5c.
954
Org. Lett., Vol. 15, No. 4, 2013

which was converted into 7 upon reaction with 2 (step C).
The perfect regioselectivity observed in the reaction of
alkyl(aryl)alkynes, phenylacetylene, or alkenes would be
attributable to the exclusive introduction of the copper
moiety to the more substituted carbon (step A), which is
induced by the electronic directing effect of the substitu-
ents (phenyl, silyl, and boryl groups).5f,m
carbon electrophiles to provide diverse multisubstituted
borylalkenes in a straightforward manner. Moreover, the
versatility of the copper catalysis toward the carbobora-
tion has been demonstrated by its application to simple
alkenes. Further studies on three-component borylation
reactions of unsaturated hydrocarbons with other elec-
trophiles under copper catalysis are in progress.
In conclusion, we have disclosed that the three-component
carboboration of alkynes facilely proceeds under copper
catalysis by utilizing a diboron reagent and suitable
Supporting Information Available. Experimental pro-
cedure including spectroscopic and analytical data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(17) Daini, M.; Suginome, M. J. Am. Chem. Soc. 2011, 133, 4758.
(18) For copper-catalyzed hydroboration of alkenes, see ref 5h.
(19) Catalyst screening in the reaction using styrene (5c): IiPrCuCl,
60% (1 h); CuIꢀxantphos, 47% (0.5 h); CuIꢀPCy3, 45% (0.5 h).
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 4, 2013
955