Palladium-catalyzed carboboration of alkynes using chloroborane and organozirconium reagents

Article abstract of DOI:10.1039/b809433k

Three-component coupling of bis(dialkylamino)chloroborane, alkynes and organozirconium reagents proceeded in the presence of palladium catalysts, leading to the formation of stereo-defined alkenylborane derivatives via cis-carboboration of carbon-carbon t

Full text of DOI:10.1039/b809433k

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Palladium-catalyzed carboboration of alkynes using chloroborane
and organozirconium reagentsw
Masaki Daini and Michinori Suginome*
Received (in Cambridge, UK) 3rd June 2008, Accepted 16th July 2008
First published as an Advance Article on the web 12th September 2008
DOI: 10.1039/b809433k
Three-component coupling of bis(dialkylamino)chloroborane,
alkynes and organozirconium reagents proceeded in the presence
of palladium catalysts, leading to the formation of stereo-defined
Scheme 1 Palladium-catalyzed cis-carboboration of alkynes using
chloroborane and organozirconium reagents.
alkenylborane derivatives via cis-carboboration of carbon–carbon
triple bonds.
Organoboronic acid derivatives play important roles in syn-
thetic organic chemistry.1 Their high synthetic value primarily
relies on the availability of a variety of organoboron-based
transformation reactions, including Suzuki–Miyaura cross-
coupling,2 Rh-catalyzed conjugate addition,3 the Petasis
reaction,4 etc. To take full advantage of the characteristic
reactivity of the organoboronic acid derivatives, exploration
of new methods for their synthesis is highly desirable.5
bonds undergoing carboboration are tethered to a chloro-
borane moiety. Tethering the alkyne and the chloroborane
moieties has significantly facilitated the reaction, although it
narrows the substrate scope. Herein, we wish to report a three-
component carboboration of alkynes, in which diaminochlor-
oboranes and organozirconium reagents are used as the sources
of the boron and organic substituents, respectively (Scheme 1).
As haloboranes employed in the optimization, we chose
monohalobis(dialkylamino)borane derivatives 1a–e, which
showed much lower Lewis acidity than trihaloboranes, which
have been used in uncatalyzed haloboration reactions.15 In
fact, the diaminohaloborane derivatives did not react at all
with alkynes at 120 1C in toluene for 12 h either in the absence
or presence of palladium catalysts. To pursue the optimum set
of reagents, we initially carried out the reactions of 4-octyne
and hexen-1-yldicyclopentadienylzirconium chloride with
chloroboranes 1a–e in the presence of palladium catalysts
carrying several different phosphine ligands (Table 1). In the
reactions of N,N0-dimethylethylenediamine-derived chloro-
borane 1a, trimethylphosphine served as the best yielding
ligand (entry 1). The reaction proceeded at 120 1C within
12 h, affording the alkenylboration product 4aaa in 93% yield
with high stereoselectivity for cis-addition. It is important to
note that use of a smaller amount (3 equiv.) of 4-octyne
resulted in a significant decrease in yield (entry 2). Use of more
bulky phosphine ligands such as tricyclohexylphosphine and
tri-t-butylphosphine gave lower yields of products (entries 3
and 4). Triphenylphosphine and bidentate phosphine ligands
such as dppe and dppf afforded the corresponding product in
moderate yields (entries 5–7). We then varied the diamine
ligands of chloroboranes. By increasing the bulkiness of the
alkyl groups on the nitrogen atoms of ethylenediamine, yields
decreased significantly (entries 8 and 9). Bicyclic chloroboranes
derived from 1,2-diaminocyclohexane and phenylenediamine
afforded the alkenylboration products 4daa and 4eaa in
moderate yields (entries 10 and 11). Although phenylboronic
acid, phenyltrimethylsilane, and phenyltriisopropoxytitanium
were tested in place of organozirconium reagent, no carbo-
boration product was detectable in the reaction mixtures.
Under the optimized reaction conditions, other alkynes
were reacted with hexen-1-ylzirconium reagent (Table 2). To
The transition metal-catalyzed borylation reaction is
regarded as one of the most efficient and selective means for
the synthesis of organoboronic acid derivatives. Besides the
catalytic hydroboration,6 additions of boron–element bonds
across carbon–carbon multiple bonds, in which functional
groups are selectively introduced in the close proximity of
the boryl groups, have been developed.7 Our effort has focused
on the development of transition metal-catalyzed additions of
element–boron bonds, such as a silicon–boron bond, to
carbon–carbon unsaturated bonds.8 These reactions provide
new routes to highly functionalized organoboron compounds
that are otherwise difficult to synthesize.
Our recent interest concerns catalytic carboborations, in
which a B–C and a C–C bond are created simultaneously on
unsaturated organic molecules. Uncatalyzed variants of the
reaction9 have been achieved only by using highly reactive
triorganoboranes such as triallylborane10 or unsaturated car-
bon compounds such as bisstannylethyne.11 We have recently
achieved a catalytic carboboration reaction through activation
of the boron–carbon bond of cyanoboranes and alkynyl-
boranes, which led to cyanoboration12 and alkynylboration13
of alkynes, respectively. We more recently established another
mode of catalytic carboboration, in which the organic and the
boryl groups are provided by organometallic reagents and
chloroboranes, respectively.14 In the previous reports, we used
a two-component system in which the carbon–carbon triple
Department of Synthetic Chemistry and Biological Chemistry, Graduate
School of Engineering, Kyoto University Katsura, Nishikyo-ku, Kyoto
615-8510, Japan. E-mail: suginome@sbchem.kyoto-u.ac.jp;
Fax: +81-75-383-2722; Tel: +81-75-383-2723
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization data for new compounds. See DOI:
10.1039/b809433k
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Table
1
Palladium-catalyzed
intermolecular
carboboration
Table
2
Palladium-catalyzed intermolecular carboboration of
of 4-octyne with chloroboranes 1a–e and hexenylzirconium 3aa
alkynes 2a-d with chloroborane 1a and organozirconiums 3a–ga
Alkyne
(R1, R2)
Organozirconium
(R3, R4)
% Yieldb
(product)
Equiv.
of 2a
% Yieldb
(product)
Entry
Entry
1
Chloroborane 1
(1a)
Ligand
PMe3
1
2
3
4
5
6
7
8
9
10
a
2a (Pr, Pr)
2b (H, Bu)
2c (H, t-Bu)
2d (Me, Ph)
2b
2b
2b
2b
2b
2b
3a (H, Bu)
3a
3a
89 (93) (5aaa)
75 (86) (5aba)
51 (63) (5aca)
66 (77) (5ada)
82 (91) (5abb)
85 (92) (5abc)
76 (85) (5abd)
68 (77) (5abe)
64 (71) (5abf)
73 (82) (5abg)
10
93 (4aaa)
3a
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
3
10
10
10
10
10
10
PMe3
PCy3
PBut3
PPh3
dppe
dppf
55 (4aaa)
32 (4aaa)
28 (4aaa)
63 (4aaa)
57 (4aaa)
69 (4aaa)
78 (4baa)
3b (H, Ph)
3c (H, p-MeOC6H4)
3d (H, p-CF3C6H4)
3e (H, TMS)
3f (H, t-Bu)
3g (Pr, Pr)
PMe3
A mixture of chloroborane 1a (0.20 mmol), alkyne (2.0 mmol),
alkenyldicyclopentadienylzirconium chloride (0.30 mmol), Cp(allyl)Pd
(0.010 mmol), and PMe3 (0.020 mmol) in toluene was heated at 120 1C
for 12 h under a nitrogen atmosphere. After removal of the solvent
in vacuo, pinacol (2.0 mmol) and TsOH (0.60 mmol) were added.
(1b)
9
10
10
PMe3
PMe3
16 (4caa)
40 (4daa)
(1c)
b
Isolated yield. NMR yield is in parentheses.
10
(1d)
Further synthetic utility was demonstrated by an arylbora-
tion reaction using arylzirconium reagents 6 (Table 3). Phe-
nylzirconium and its p-substituted derivatives afforded the
corresponding arylboration products 7 in good yields with
high stereoselectivity for cis-addition. Under the current reac-
tion conditions, however, alkylzirconium compounds failed to
take part in the carboboration reaction.
11
10
PMe3
55 (4eaa)
(1e)
a
A mixture of chloroborane (0.20 mmol), 4-octyne (amount indicated
in the table), hexen-1-yldicyclopentadienylzirconium chloride
(0.30 mmol), Cp(allyl)Pd (0.010 mmol), and a phosphine ligand
(0.020 mmol for entries 1–5 and 8–11, 0.010 mmol for entries 6 and
7) in toluene was heated at 120 1C for 12 h under a nitrogen
atmosphere. The alkenylzirconium reagent was prepared by the reac-
tion of 1-hexyne with Cp2ZrHCl and used after evaporation of the
The carboboration product 5aaa was successfully coupled
with p-tolyl bromide under the Suzuki–Miyaura coupling
b
solvent without further purification. NMR yield using an internal
standard.
Table
3 Palladium-catalyzed intermolecular carboboration of
alkynes 2a,b with chloroborane 1a and arylzirconiums 6a–ca
make the isolation easier, the diamine ligand on the boron
atom was replaced with a pinacol ligand in situ after comple-
tion of the carboboration step. The adduct 5aaa derived from
4-octyne and hexen-1-ylzirconium was isolated in 89% yield
by silica gel column chromatography (entry 1).z Terminal
alkynes (R1 = H) such as 1-hexyne and t-butylacetylene
afforded the corresponding carboboration products, in which
the boron atom is attached to the terminal position, in high
yields with high regio- and stereoselectivity (entries 2 and 3).
1-Phenylpropyne afforded the product in which the
boryl group is attached selectively to the methyl-substituted
carbon atom (entry 4). Various alkenylzirconium reagents
could be used in the reactions with 1-hexyne. b-Styrylzirco-
nium reagents with or without p-substituents (entries 5–7),
b-silylethenyl (entry 8), b-t-butylvinyl (entry 9), and 4-octen-
4-ylzirconium (entry 10) reagents afforded the corresponding
dienylborane derivatives in good isolated yields.16
Alkyne
Organozirconium
(Ar)
% Yieldb
(product)
Entry
(R1, R2)
1
2
3
4
5
6
a
2a (Pr, Pr)
2a
2a
2b (H, Bu)
2b
2b
6a (Ph)
6b (p-MeOC6H4)
6c (p-CF3C6H4)
6a
6b
6c
92 (97) (7aaa)
89 (96) (7aab)
81 (89) (7aac)
82 (90) (7aba)
82 (93) (7abb)
77 (87) (7abc)
A mixture of chloroborane 1a (0.20 mmol), alkyne (2.0 mmol),
aryldicyclopentadienylzirconium chloride (0.30 mmol), Cp(allyl)Pd
(0.010 mmol), and PMe3 (0.020 mmol) in toluene was heated at
120 1C for 12 h under a nitrogen atmosphere. After removal of the
solvent in vacuo, pinacol (2.0 mmol) and TsOH (0.60 mmol) were
b
added. Isolated yield. NMR yield is in parentheses.
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CH2Cl2 (0.3 mL) at room temperature. The mixture was stirred for 3 h
at room temperature, and then the volatile material was removed in
vacuo, leaving hexen-1-yldicyclopentadienylzirconium chloride 3a as
the residue. In another flask, Cp(p-allyl)Pd (0.010 mmol) and PMe3
(0.020 mmol) were dissolved in toluene (0.05 mL). Chloroborane 1a
(0.20 mmol), 4-octyne 2a (2.0 mmol), and a solution of 3a (0.30 mmol)
in toluene (0.05 mL) were added to the catalyst solution. The mixture
was heated at 120 1C for 12 h under a nitrogen atmosphere. After
removal of the solvent in vacuo, pinacol (2.0 mmol), THF (0.3 mL),
and TsOH (0.60 mmol) were added, and the mixture was stirred for 3 h
at room temperature. The mixture was passed through a pad of
Florisils, and the solvent was removed in vacuo. The residue was
purified by silica gel column chromatography (hexane : EtOAc =
20 : 1), affording cis-alkenylboration product 5aaa in 89% yield.
Scheme 2 Suzuki–Miyaura coupling of 5aaa with aryl halide.
1 D. Hall, in Boronic Acid, ed. D. Hall, Wiley, Weinheim, 2005, p. 1.
2 (a) N. Miyaura, Top. Curr. Chem., 2002, 219, 11; (b) N. Miyaura
and A. Suzuki, Chem. Rev., 1995, 95, 2457.
3 (a) M. Sakai, H. Hayashi and N. Miyaura, Organometallics, 1997,
16, 4229. Reviews: ; (b) K. Fagnou and M. Lautens, Chem. Rev.,
2003, 103, 169; (c) T. Hayashi and K. Yamasaki, Chem. Rev., 2003,
103, 2829.
4 (a) N. A. Petasis and I. Akritopoulou, Tetrahedron Lett., 1993, 34, 583;
(b) N. A. Petasis and I. A. Zavialov, J. Am. Chem. Soc., 1997, 119, 445.
5 A. Suzuki and H. C. Brown, Organic Synthesis via Boranes,
Aldrich, Milwaukee, WI, 2003, vol. 3.
6 Catalytic hydroborations: (a) H. Noth and D. Mannig, Angew.
¨
¨
Chem., Int. Ed. Engl., 1985, 24, 878; For reviews, see: (b) K.
Burgess and M. J. Ohlmeyer, Chem. Rev., 1991, 91, 1179; (c) I.
Beletskaya and A. Pelter, Tetrahedron, 1997, 53, 4957; (d) C. M.
Crudden and D. Edwards, Eur. J. Org. Chem., 2003, 24, 4695.
7 Reviews on the catalytic boron–element addition: (a) T. B. Marder
and N. C. Norman, Top. Catal., 1998, 5, 63; (b) T. Ishiyama and N.
Miyaura, J. Organomet. Chem., 2000, 611, 392; (c) T. Ishiyama and
N. Miyaura, Chem. Rec., 2004, 3, 271; (d) V. M. Dembitsky, H.
Abu Ali and M. Srebnik, Adv. Organomet. Chem., 2004, 51, 193; (e)
I. Beletskaya and C. Moberg, Chem. Rev., 2006, 106, 2320; (f) M.
Suginome, T. Matsuda, T. Ohmura, A. Seki and M. Murakami, in
Comprehensive Organometallic Chemistry III, ed. R. Crabtree, M.
Mingos and I. Ojima, Elsevier, Oxford, 2007, vol. 10, p. 725.
8 (a) M. Suginome, H. Nakamura and Y. Ito, Chem. Commun., 1996,
2777; (b) T. Ohmura, H. Taniguchi and M. Suginome, J. Am.
Chem. Soc., 2006, 128, 13682; (c) T. Ohmura, H. Furukawa and M.
Suginome, J. Am. Chem. Soc., 2006, 128, 13366; (d) T. Ohmura, H.
Taniguchi, Y. Kondo and M. Suginome, J. Am. Chem. Soc., 2007,
129, 3518.
Scheme 3 A possible mechanism for the palladium-catalyzed carbo-
boration of alkynes using chloroborane and organozirconium reagents.
conditions using P(t-Bu)3 as a ligand,17 giving 1-aryl-1,3-diene
8 in high yield (Scheme 2).
The mechanism of the present carboboration reaction is
postulated on the basis of the reported stoichiometric reaction
of chloroboranes with palladium complexes (Scheme 3).18,19
Oxidative addition of the B–Cl bond to palladium affords boryl-
chlorobis(phosphine)palladium(II) intermediate A, which under-
goes insertion of alkynes at the B–Pd bond, resulting in the
formation of (b-borylalkenyl)chloropalladium(II) intermediate C.
The alkenylpalladium intermediate C does not undergo reductive
elimination, but reacts with organozirconium compounds, giving
a diorganopalladium intermediate D from which the carbobora-
tion products are produced via reductive elimination.
9 P. Knochel, in Comprehensive Organic Synthesis, ed. B. M. Trost,
Pergamon Press, Oxford,1991, vol. 4, p. 865.
10 B. M. Mihailov and Y. N. Bubnov, Tetrahedron Lett., 1971, 4597
and references therein.
In summary, we found a new palladium-catalyzed three-
component coupling reaction of diaminochloroboranes,
alkynes, and organozirconium reagents that afforded cis-
carboboration products in good yields. Terminal alkynes and
1-phenylpropyne undergo the carboboration regioselectively,
giving products in which the boryl group is attached to the less
sterically hindered position. Further modifications to the
reaction conditions and reagents are now being undertaken
in our laboratory to expand the substrate scope and to reduce
the amounts of alkynes needed.
11 B. Wrackmeyer and H. Noth, J. Organomet. Chem., 1976, 108, C21.
¨
12 (a) M. Suginome, A. Yamamoto and M. Murakami, J. Am. Chem.
Soc., 2003, 125, 6358; (b) M. Suginome, A. Yamamoto and M.
Murakami, Angew. Chem., Int. Ed., 2005, 44, 2380; (c) M.
Suginome, A. Yamamoto, T. Sasaki and M. Murakami,
Organometallics, 2006, 25, 2911.
13 M. Suginome, M. Shirakura and A. Yamamoto, J. Am. Chem.
Soc., 2006, 128, 14438.
14 (a) A. Yamamoto and M. Suginome, J. Am. Chem. Soc., 2005, 127,
15706; (b) M. Daini, A. Yamamoto and M. Suginome, J. Am.
Chem. Soc., 2008, 130, 2918.
15 S. Hara, T. Kato, H. Shimizu and A. Suzuki, Tetrahedron Lett.,
1985, 26, 1065.
This work is supported by a Grant-in-Aid for Scientific
Research on Priority Areas ‘‘Advanced Molecular Transfor-
mations of Carbon Resources’’ from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan.
16 For selected synthetic applications of dienylboranes, see: (a) P.-Y.
Renard, Y. Six and J.-Y. Lallemand, Tetrahedron Lett., 1997, 38,
6589; (b) X. Gao and D. Hall, Tetrahedron Lett., 2003, 44, 2231; (c)
G. Hilt, W. Hess and K. Harms, Org. Lett., 2006, 8, 3287; (d) M.
Tortosa, N. A. Yakelis and W. R. Roush, J. Am. Chem. Soc., 2008,
130, 2722.
17 A. F. Littke, C. Dai and G. C. Fu, J. Am. Chem. Soc., 2000, 122, 4020.
18 S. Onozawa and M. Tanaka, Organometallics, 2001, 20, 2956.
19 A catalytic reaction that involves oxidative addition of in situ generated
B–I to palladium was reported. See: F.-Y. Yang and C.-H. Cheng,
J. Am. Chem. Soc., 2001, 123, 761; K.-J. Chang, D. K. Rayabarapu,
F.-Y. Yang and C.-H. Cheng, J. Am. Chem. Soc., 2005, 127, 126.
Notes and references
z General procedure for Pd-catalyzed intermolecular carboboration of
alkynes with chloroboranes and organozirconiums: 1-Hexyne (25 mg,
0.30 mmol) was added to Cp2ZrHCl (77 mg, 0.30 mmol) suspended in
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This journal is The Royal Society of Chemistry 2008
5226 | Chem. Commun., 2008, 5224–5226