RhCl3-catalyzed hydroboration of alkenyl nitriles

Article abstract of DOI:10.1016/S0040-4039(03)01522-3

RhCl₃-promoted hydroboration-oxidation reactions of representative alkenyl nitriles have been carried out. Carbanion of acetonitrile is formed from the carbon-carbon heterolytic bond breaking in allyl cyanide during hydroboration. An unexpected process-trimerization of carbanion of acetonitrile has lead to the formation of 4-amino-2,6-dimethylpyrimidine.

Full text of DOI:10.1016/S0040-4039(03)01522-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6301–6304
RhCl3-catalyzed hydroboration of alkenyl nitriles
Anvar U. Buranova,* and Terence C. Morrillb,*
aDepartment of Organic Synthesis, Institute of the Chemistry of Plant Substances, Tashkent 700170, Uzbekistan
bDepartment of Chemistry, College of Science, Rochester Institute of Technology, Rochester, NY 14623, USA
Received 16 February 2003; revised 17 June 2003; accepted 18 June 2003
Abstract—RhCl3-promoted hydroboration–oxidation reactions of representative alkenyl nitriles have been carried out. Carbanion
of acetonitrile is formed from the carbonꢀcarbon heterolytic bond breaking in allyl cyanide during hydroboration. An unexpected
process-trimerization of carbanion of acetonitrile has lead to the formation of 4-amino-2,6-dimethylpyrimidine.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
dures.12–14 Therefore, catalyzed hydroborations of alke-
nes have been studied extensively,15–17 but catalyzed
hydroborations of alkenyl nitriles have never been stud-
ied in detail.18 Our previous studies on the hydrobora-
tion of 1-octene in the presence of rhodium trichloride
(RhCl3) showed unusual regioselectivity.19 Therefore, it
seems appropriate to study the hydroboration reactions
of alkenyl nitriles in the presence of rhodium trichlo-
ride, since they have two reactive centers for hydrobo-
ration reactions: the carbonꢀcarbon double bond and
carbon-nitrogen triple bond. We have chosen the fol-
lowing alkenyl nitriles for hydroboration reactions: allyl
cyanide, acrylonitrile and 5-hexenenitrile.
Hydroboration reactions of alkenes containing func-
tional groups such as alkenyl amines,1 alkenyl chlo-
rides,2 alkenyl alcohols,3 and their ethers,4 and alkenyl
amino-acids5 have been extensively studied since the
functional groups can serve as chiral auxiliaries in the
asymmetric induction and they have wide applications
in the enantio-selective synthesis of natural products.6,7
Hydroboration of aliphatic and aromatic nitriles yield
borazine derivatives which can be hydrolyzed to the
amines.8–11 Transition metal-catalyzed hydroboration
reactions are widely applicable to the synthetic proce-
Scheme 1.
* Corresponding authors. Tel.: 998-71-162-700; fax: 998-71-120-6475; e-mail: buranov71@yahoo.com (A.U.B.); Tel.: 716-475-2497; fax: 716-475-
7800; e-mail: icps2@uzsci.net; tcmsch@rit.edu (T.C.M.)
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01522-3

6302
A. U. Burano6, T. C. Morrill / Tetrahedron Letters 44 (2003) 6301–6304
2. Hydroboration of allyl cyanide
Initially butyramide and methacrylamide are formed
and then the formation of 4-amino-2,6-dimethylpyrim-
idine, ethanol, and acetonitrile occurs. The cleavage of
allyl cyanide and the trimerization of the newly formed
acetonitrile give rise to the formation of 4-amino-2,6-
dimethylpyrimidine. However, the hydroboration of
acetonitrile under the same conditions did not yield
4-amino-2,6-dimethylpyrimidine.8–11 This fact allowed
us to conclude that the carbonꢀcarbon bond cleavage
occurs heterolytically and the acetonitrile carbanion
and ethyl cation are formed. The highly reactive and
unstable carbanions of acetonitrile undergoes trimeriza-
tion process by forming 4-amino-2,6-dimethylpyrim-
idine (Scheme 2). The relatively high yield (10.5%) for
the 4-amino-2,6-dimethylpyrimidine was achieved when
the reaction kept going for 1.5 h (exp. 4). Longer
reaction times favored butyramide. We propose the
following possible mechanism for the formation of
4-amino-2,6-dimethylpyrimidine from the carbanion of
acetonitrile (Scheme 2).
The hydroboration of allyl cyanide in the presence of
RhCl3 and further oxidation lead to the following
transformations (Scheme 1).
(a) Heterolytic cleavage of CꢀC bond and the trimer-
ization of acetonitrile carbanion;
(b) Isomerization;
(c) Hydrogenation.
Three compounds can be formed in the result of
hydroboration-oxidation reaction of allyl cyanide in the
presence of RhCl3: 4-amino-2,6-dimethylpyrimidine 1,
methacrylamide 2 and butyramide 3. These compounds
are the results of different chemical processes. For
example: 4-amino-2,6-dimethylpyrimidine is formed
during the trimerization of acetonitrile carbanion
obtained in the result of the carbonꢀcarbon bond cleav-
age of allyl cyanide. Butyramide can be obtained as the
result of the hydrogenation of the double bond in the
allyl cyanide and methacrylamide via the isomerization
of allyl cyanide. The nitrile group in the allyl cyanide is
hydrolyzed to an amide group.
The reactive RhꢀBꢀH species first proposed by Mannig
and Noth20 are likely involved in our proposed mecha-
nism. The availability of two reactive centers in the allyl
cyanide molecule, the carbonꢀcarbon double bond and
carbonꢀnitrogen triple bond, allows the addition of
RhꢀBꢀH species at both centers. These additions cause
the carbonꢀcarbon bond in allyl cyanide break (Scheme
3) heterolytically because of the torsional strain
between hydroborated carbonꢀcarbon double bond and
carbonꢀnitrogen triple bond and as a result two reac-
tive species such as hydroborated carbanion of acetoni-
trile and ethyl carbocation are formed. The carbanion
of acetonitrile is bonded to the RhꢀBꢀH species on the
nitrogen end of the carbonꢀnitrogen triple bond and to
the nucleophilic carbon of this carbanion. The RhꢀBꢀH
These compounds can be selectively synthesized by
changing the ratio of starting materials (Table 1).
The ratio of starting compounds is an important factor
for the reaction control. The selective synthesis of one
compound can be achieved by changing the ratio of
starting materials. Table 1 shows that the optimal ratio
of reactants for the selective synthesis of the corre-
sponding compounds.
The hydroboration of allyl cyanide has been carried out
varying the hydroboration period (Table 2).
Table 1. Hydroboration of allyl cyanide with borane in the presence of RhCl3
Exp. c
Allyl cyanide
(ml)
Borane (ml)
Volume ratio
Mole ratio
Total yield (%) Yield of ethanol Yield of products
(%)
3/2/1 (%)
1
2
3
4
5
6
7
8
9
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
15.00
10.00
5.00
3.00
2.00
1.00
0.50
0.25
0.00
1:15
1:10
1:5
1:3
1:2
1:1
2:1
4:1
1:0
1:1.5
1:1
60
60
55
40
40
61
50
60
20
15
16
10
3.4
12
4.6
2.4
2.4
1.9
13.6/0.0/71.3
31.3/0.0/52.3
68.2/0.0/22.0
58.7/33.4/4.4
71.4/16.3/0.0
0.0/95.4/0.0
0.0/97.6/0.0
0.0/97.6/0.0
0.0/98.1/0.0
1:0.5
1:0.3
1:0.2
1:0.1
1:0.05
1:0.025
1:0.00
Table 2. Hydroboration of allyl cyanide for different reaction period (in %) (mole ratio of allyl cyanide:borane 1:0.3)
Exp. c Time (h)
Butyramide
Methacrylamide Uncoupled acetonitrile
Ethanol
4-Amino-2,6-dimethylpyrimidine
1
2
3
4
5
6
7
0.25
0.50
1.00
1.50
2.00
3.00
5.00
68.00
54.68
51.20
33.34
45.00
68.40
80.60
32.00
30.32
17.30
13.34
25.50
10.30
14.50
0.00
2.00
2.00
5.70
8.00
10.60
2.50
0.00
11.00
22.6
37.00
18.00
10.60
2.50
0.00
3.00
6.80
10.50
3.34
2.54
3.00

A. U. Burano6, T. C. Morrill / Tetrahedron Letters 44 (2003) 6301–6304
6303
Scheme 2.
Scheme 3.
intermediate migrates reversibly via these tautomeric
forms (Scheme 4).
ble bond of acrylonitrile. In this reaction the car-
bonꢀcarbon double bond gets reduced but
carbonꢀnitrogen triple bond remains unchanged.
Hydrolysis converts nitrile group into amide group.
Both room temperature and reflux conditions also
afforded the same product (Scheme 5).
The unsaturated centers in acrylonitrile that are close to
each other afford only one hydrogenated product. The
competition between carbonꢀcarbon double bond and
carbonꢀnitrogen triple bond results in the hydrogena-
tion of the former. The absence of carbonꢀcarbon bond
breaking can be explained by this competition and
steric hindrance within acrylonitrile.
Scheme 4.
These two reactive species undergo trimerization to
form the organoborane adduct of 4-amino-2,6-
dimethylpyrimidine. Further hydrolysis of this adduct
affords 4-amino-2,6-dimethylpyrimidine. The hydrolysis
of ethyl carbocation results in ethanol.
4. Hydroboration of 5-hexenenitrile
3. Hydroboration of acrylonitrile
Hydroboration of 5-hexenenitrile 7 gave net hydration
product 8 on the carbonꢀcarbon double bond. This
reaction is an example of the hydroboration preference
Hydroboration of acrylonitrile 4 yields propionamide 6,
the hydrogenation product of the carbonꢀcarbon dou-

6304
A. U. Burano6, T. C. Morrill / Tetrahedron Letters 44 (2003) 6301–6304
Scheme 5.
Scheme 6.
between carbon-carbon double bond and car-
bonꢀnitrogen triple bond. Hydroboration favored to net
hydration of carbonꢀcarbon double bond in accord with
anti-Markovnikov addition (Scheme 6). The car-
bonꢀcarbon bond breaking is not observed in this
because of the lack of torsional strain between hydrob-
orated double and triple bonds.
Asymmetry 2000, 11, 2133–2142.
2. Brown, H. C.; Keblys, K. A. J. Am. Chem. Soc. 1964,
86, 1791.
3. Brown, H. C.; Cope, O. J. J. Am. Chem. Soc. 1964, 86,
1801.
4. Dhanabalan, M.; Singaram, B.; Brown, H. C Tetra-
hedron: Asymmetry 2000, 11, 4831–4834.
5. Collier, P. N.; Campbell, A. D.; Patel, I.; Taylor, R. J.
K. Tetrahedron 2002, 58, 6117–6125.
6. Ng, F.; Chiu, P.; Danishefsky, S. J. Tetrahedron Lett.
1998, 39, 767–770.
7. Clark, J. S.; Kettle, J. G. Tetrahedron Lett. 1997, 38,
123.
8. Brown, H. C.; Subba Rao, B. C. J. Am. Chem. Soc.
1960, 82, 681.
9. Emeleus, H. J.; Wade, K. J. Chem. Soc., Abstracts
1960, 2614–2617.
10. Hawthorne, M. F. Tetrahedron 1962, 17, 117–122.
11. Lane, C. F. Chem. Rev. 1976, 76, 773–799.
12. Evans, D. A.; Fu, G. C.; Mucl, A. R. Advances in
Catalytic Processes; Greenwich, CT, 1995; Vol. 1, pp.
95–121.
13. Burgess, K.; Ohlmeyer, M. J. Chem. Rev. 1991, 91,
1179.
14. Pelter, A.; Beletskaya, I. Tetrahedron 1997, 53, 4957.
15. Hayashi, T.; Matsumoto, Y.; Ito, Y. J. Am. Chem. Soc.
1989, 111, 3426.
16. Evans, D. A.; Fu, G. C. J. Org. Chem. 1990, 55, 2280.
17. Burgess, K.; van der Donk, W. A.; Jarstfer, M. B.;
Ohlmeyer, M. J. J. Am. Chem. Soc. 1991, 113, 6139.
18. Brown, H. C.; Ramachandra, P. V. Advances in Asym-
metric Synthesis 1995, 1, 150.
General hydroboration procedure: In the flask equipped
with a condenser, under nitrogen 10 mg of RhCl3 was
dissolved in 10 ml of freshly distilled tetrahydrofuran and
1.0 ml (0.0125 mol) of allyl cyanide was added. After 10
min of stirring, 15 ml (0.15 mol) or required amount of
0.1 M BH3 in THF was added to the solution using a
syringe. The reaction mixture was stirred at room tem-
perature for 2 h. Then 10 ml of 30% H2O2 was added
followed by 10 ml of 3 M NaOH at 0°C. After 4 h the
solution was filtered and extracted with 40 ml of diethyl
ether three times. Solvent was removed with rotator
evaporator to obtain the final product. The structures
were confirmed with GC/MS and NMR.
4-Amino-2,6-dimethylpyrimidine. 1H NMR (400 MHz,
DMSO-d6): l (ppm)=6.63 (2H, d, J=2.5 Hz, NH), 6.086
(1H, s, J=2.3 Hz, arom. H), 2.272 (3H, d, J=2.6 Hz),
2.152 (3H, s); MS m/z (%): 123 (M+, 100); 68 (30); 56 (50).
Acknowledgements
The ‘UMID’ foundation of the Republic of Uzbekistan
and the Chemistry Department of RIT are gratefully
acknowledged for the financial support to this research.
19. Morrill, T. C.; D’Souza, C. A.; Yang, L.; Sampognaro,
A. J. J. Org. Chem. 2002, 67, 2481–2484.
20. Mannig, D.; Noth, H. Angew Chem., Int. Ed. Engl.
1985, 24, 878.
References
1. Pennemann, H.; Wallbaum, S.; Martens, J. Tetrahedron: