Synthesis of dialkyl cyanoboronates and their application in palladium-catalyzed cyanation of aryl halides

Article abstract of DOI:10.1016/S0040-4020(00)01139-X

A new type of cyanoboronate 4 was prepared and used as a new cyano group source in palladium-catalyzed cyanations of aryl and heteroaryl halides to afford the corresponding aryl and heteroaryl nitriles.

Full text of DOI:10.1016/S0040-4020(00)01139-X

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1581±1584
Synthesis of dialkyl cyanoboronates and their application
in palladium-catalyzed cyanation of aryl halides
Biao Jiang,p Ying Kan and Ao Zhang
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, People's Republic of China
Received 21 September 2000; revised 15 November 2000; accepted 30 November 2000
AbstractÐA new type of cyanoboronate 4 was prepared and used as a new cyano group source in palladium-catalyzed cyanations of aryl
and heteroaryl halides to afford the corresponding aryl and heteroaryl nitriles. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
preparation of aryl and heteroaromatic nitriles, has not been
well developed. Furthermore, there is no report about the
application of dialkyl cyanoboronate as the cyanide source
in the palladiun-mediated cyanation, although potassium,
sodium, trimethylsilyl and zinc cyanides have been used
widely. In this paper we introduce the synthesis of dialkyl
cyanoboronates and their application as a new cyanide
source in palladium-catalyzed cyanation.
Aryl nitriles are very important materials because of their
wide applications in laboratory and industry studies.
Various methods have been reported for their synthesis.1
The most convenient one is the stoichiometric reaction of
aryl halides with copper(I) cyanide at high temperature, but
the product isolation is very troublesome due to the for-
mation of the copper complex in the course of reaction.2
The Reissert±Henze cyanation of p-de®cient heteroarene
N-oxides,3 and the electrophilic cyanation of p-excessive
heteroaromatics4 are also known as ef®cient methods for
preparation of aryl and heteroaryl cyanides. But these
methods have proven to be of limited use for some speci®c
substrates.
2. Results and discussions
Cyanoboronate derivatives are new types of organoboron
compounds, the preparation and properties of which have
been not reported up to now in any literatures.10±14 In our
initial studies, we wanted to synthesize cyclic dialkyl cyano-
boronate 3 (Scheme 1), by treatment of 1,2-dihydroxy
compound 2 with one equivalent of sodium cyanoboro-
hydride NaBH3CN 1. But as a result, we found acyclic
compound 4 was produced and no cyclic compound 3 was
observed. More interestingly, dialkyl cyanoboronate 4 was
obtained as the single product whether one or two equiva-
lents of 1,2-dihydroxy compound 2a or 2b was used in the
Palladium-catalyzed displacement of aryl halides and
tri¯ates with cyanide ion to afford the corresponding aryl
nitrile has been reported as a more favorable alternative.5,6
Although many modi®cations5c±d,7±9 have been developed
about the ligand sets, the use of covalent or the cyano group
sources, these procedures have only been useful for the
preparation of benzonitrile derivatives.6 A general pro-
cedure of palladium-catalyzed cyanation, applicable to the
Scheme 1.
Keywords: dialkyl cyanoboronate; palladium; cyanation; aryl halide.
Corresponding author. Tel.: 186-21-6416-3300; fax: 186-21-6416-6128; e-mail: jiangb@pub.sioc.ac.cn
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01139-X

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B. Jiang et al. / Tetrahedron 57 (2001) 1581±1584
As shown above, the best result was obtained by using Pd
(PPh3)4 as the catalyst (entry 4), the yields dropped signi®-
cantly when PdCl2(Ph3P)4 was used. Potassium phosphate
was the best choice of base over other organic and inorganic
bases. THF was a better solvent than toluene in this reaction.
Under these optimum conditions, we expanded the cya-
nation reaction to other aryl and heterocyclic aryl halides.
The results are described in Table 2.
Scheme 2.
reaction. Under the same conditions, treating 2c with
compound 1 afforded compound 4c (Scheme 2).
As shown in Table 2, most of aryl halides react with dialkyl
cyanoboronate 4 to afford the corresponding nitrile products
(entries 1±10), but the cyanation reaction proceeded slowly
and the yields changed widely according to different sub-
stituents in the aryl halide substrates. It was reported15 the
treatment of 1-chloro-3-iodobenzene with KCN in HMPA
in the presence of palladium acetate afforded a mixture of
3-chlorobenzonitrile and 1,3-benzenedicarbonitrile (77:23),
while in our system 4-chloro-1-iodobenzene and 1,4-di-
iodobenzene gave 4-chloro-benzonitrile and 4-iodobenzo-
nitrile as the single product, respectively. No dicyanation
products were detected (entries 3±4), but the yields were
unsatisfactory. At the same time, heteroaryl halides, such as
2-iodo-thiophene (entry 12) and N-methylsulfonyl-3-iodo-
indole (entry 11), can also react with dialkyl cyanoboronate
4 to give heteroaryl nitriles. The mechanism of the
Although the mechanism of production of compound 4 in
our reaction was unclear, it was necessary to employ
vicinal-dihydroxy compound 2. Employing simple alcohols
such as methanol, ethanol and tert-butanol in place of
1,2-dihydroxy compounds 2 gave trialkylborates and no
dialkyl cyanoboronate 4 was observed.
In order to explore the properties of dialkyl cyanoboronate
4, we carried out the cyanation reaction of compound 4 with
aryl or heterocyclic aryl halides catalyzed by palladium.
First we studied the effects of different bases, palladium
catalysts, temperature and solvents using the model reaction
of 4-bromo-1-nitro benzene with dialkyl cyanboronate 4b.
The results are summarized in Table 1.
Table 1. Effects of reaction conditions on Pd-catalyzed cynation of 4-nitro-bromobenzene with compound 4b
Entry
Base
M-complex
T (8C)
Time, days
%,Conversiona
1
2
3
4
5
6
K3PO4
K3PO4
Et3N
K3PO4
AgNO3
K3PO4
Pd(PPh3)4±PPh3
PdCl2(PPh3)2±PPh3
Pd(PPh3)4±PPh3
Pd(PPh3)4±PPh3
Pd(PPh3)4±PPh3
Pd(PPh3)4±PPh3
25b
50b
50b
50b
50b
100c
6
6
10
6
6
6
76
12
15
97
2
80
a
Conversion determined by GC±MS.
Reaction in THF.
Reaction in toluene.
b
c
Table 2. Pd-catalyzed cyantion of aryl and heterocydic aryl halides with compound 4
Entrya
Substrate
Iodobenzene
4-Trifuloromethyl-2-nitro-1-
chlorobenzene
Time
%, Convb
Product
1
2
24 h
24 h
80 (78)
40 (19)
Benzonitrile
4-Trifuloromethyl-2-
nitrobenzonitrile
3
4
5
6
7
8
9
10
11
4-Chloro-1-iodobenzene
1,4-Diiodobenzene
17 h
42 h
6 d
48 h
12 h
10 h
24 h
10 h
24 h
67 (37)
13 (10)
97 (89)
58 (50)
33 (32)
64 (60)
87 (72)
72 (69)
49 (39)
4-Chloro-benzonitrile
4-Iodobenzonitrile
4-Nitrobenzonitrile
4-Nitrobenzonitrile
2,4-Dinitro-benzonitrile
2,4-Dinitro-benzonitrile
1-Cyano-naphthalene
1-Cyano-naphthalene
N-Methylsulfonyl-3-
cyano-indole
4-Nitro-1-bromobenzene
4-Nitro-1-iodobenzene
2,4-Dinitro-1-chlorobenzene
2,4-Dinitro-1-bromobenzene
1-Bromo-naphthalene
1-Iodo-naphthalene
N-Methylsulfonyl-3-iodoindole
12
2-Iodo-thiophene
24 h
83 (75)
2-Cyano-thiophene
a
Compound 4a was used in entry 1and compound 4b was used in entries 2±12.
Conversion was determined by GC±MS and the parenthesis is the isolated yield based on starting halide.
b

B. Jiang et al. / Tetrahedron 57 (2001) 1581±1584
1583
palladium-catalyzed cyanation of dialkyl cyanoboronate 4
with aryl halides, would be similar to that of cross-coupling
reaction,6 including oxidative addition of aryl halides to
catalyst, ligand exchange of cyano anion with halogen
anion and reductive elimination.
3.1.3. Di(2-hydroxyphenyl) cyanoboronate 4c. (2.08 g,
82%); bp 173±1758C/0.1 mmHg; nmax(neat) 3451, 2299,
1364, 1192, 1095 cm21; dH (300 MHz, CDCl3) dH 6.65±
6.98 (m, Ar±H); m/z (EI) 255 (M1, 1), 254 (100), 228 (2),
109 (64%); HRMS (EI): M1, found 255.0705. C13H10NO4B
requires 255.0703. M121, found 254.0588. C13H9NO4B
requires 254.0624.
In conclusion, a new type of cyanoboronate 4 was prepared.
As a new cyano group source, they can be used in
palladium-catalyzed cyanation of aryl and heteroaryl
halides to afford the corresponding aryl and heteroaryl
nitriles, but the yields were unsatisfactory.
3.2. General procedure for palladium-catalyzed
cyanation using dialkyl cyanoboronate 4a or 4b as the
cyano group source
The substrate (0.5 mmol), dialkyl cyanoboronate 4a or 4b
(0.6 mmol), Pd(PPh3)4 (28 mg, 0.025 mmol), PPh3 (12 mg,
0.05 mmol), and anhydrous potassium phosphate (80 mg, 0.
75 mmol) were placed in a ¯ask which was ¯ushed with
Argon. Freshly redistilled THF (5 mL) was added via
syringe. The resulting mixture was heated to 508C under
argon with vigorous agitation. Then the mixture was cooled
to room temperature, diluted with diethyl ether (20 mL), and
®ltered through a pad of celite. The ®ltrate was washed with
water and brine, dried over anhydrous Na2SO4, and concen-
trated by rotary evaporation. This residue was subjected to
GC±MS for determination of the conversion, the isolated
yields were obtained after further puri®cation of the residue
by silica gel chromatography (ethyl acetate/petroleum).
3. Experimental
NMR spectra were recorded as CDCl3 solutions on a VXL-
300 instrument. The H NMR (300 MHz) chemical shifts
1
are reported as d values in ppm relative to tetramethylsilane
as internal standard. Infrared spectra were recorded on a
Perkin±Elmer 983 FT±IR spectrometer. Mass spectral
measurements were performed on a Fining 4021 or Fining
MAT 8403 gas chromatography/mass spectrometer at
70 eV. All solvents were puri®ed and dried by standard
techniques before use. NaBH3CN was purchased from
Aldrich. Pd (PPh3)4 and PdCl2(PPh3)2 were prepared
according to literature procedures.5a,16 All reactions were
monitored by thin layer chromatography (TLC) using silica
gel GF254. Products were puri®ed by chromatography on
silica gel manufactured in Qingdao Marine Chemical
Factory, eluting with the solvent mixture of petroleum
ether (bp 60±908C) and ethyl acetate.
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3.1. General procedure for the preparation of dialkyl
cyanoboronates 4
To a 08C cooled solution of sodium cyanoborohydride 1
(630 mg, 0.01 mol) and vicinal dihydroxy compound 2
(0.02 mol) in THF (4 mL), under argon was dropped a
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77%); bp 80±858C/0.1 mmHg; nmax(neat) 3401, 2265,
1399, 1349,1106, 1083 cm21; dH (300 MHz, CDCl3)
4.03±4.05 (4H, m), 4.21 (4H, t); m/z (EI) 159 (M1, 24),
157 (M122,100), 133 (M12CN, 6), 128 (M12CH2OH,
41%); HRMS (EI): M1, found: 159.0700. C5H10NO4B
requires 159.0703. M122, found 157.0512. C5H8NO4B
requires 157.0546.
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-
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(EI): M1, found 271.1953. C13H26NO4B requires 271.1955.
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