Palladium-catalyzed intramolecular cyanoboration of allenes leading to the regioselective synthesis of β-cyanoallylboranes

Article abstract of DOI:10.1016/j.tetlet.2009.01.025

Inter- and intramolecular addition of the boron-cyanide bond of cyanoboranes across a carbon-carbon double bond of allenes proceeded in the presence of palladium catalysts, affording allylboranes that bear a cyano group at the β-position regioselectively.

Full text of DOI:10.1016/j.tetlet.2009.01.025

Tetrahedron Letters 50 (2009) 3168–3170
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Palladium-catalyzed intramolecular cyanoboration of allenes leading
to the regioselective synthesis of b-cyanoallylboranes
*
Akihiko Yamamoto, Yuto Ikeda, Michinori Suginome
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Katsura, Kyoto 615-8510, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Inter- and intramolecular addition of the boron-cyanide bond of cyanoboranes across a carbon–carbon
double bond of allenes proceeded in the presence of palladium catalysts, affording allylboranes that bear
a cyano group at the b-position regioselectively.
Received 15 December 2008
Revised 6 January 2009
Accepted 9 January 2009
Available online 14 January 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Increasing attention has been focused on the efficient synthesis
of functionalized organoboronic acids, which serve as useful
synthetic intermediates in the synthesis of complex organic mole-
cules.1 Recent development of a variety of transformation reactions
of organoboronic acids, such as Suzuki–Miyaura coupling,2 rho-
dium-catalyzed conjugate addition,3 and Petasis reaction,4 has en-
hanced their utilities in organic synthesis. Further development of
more efficient and convenient method for their synthesis is eagerly
desired to take full advantages of organoboronic acids as synthetic
intermediates. Of particular interest is transition-metal-catalyzed
synthesis of organoboronic acids, which may provide synthetic
routes to new organoboron compounds that are hardly accessible
rane products albeit in low yield (Scheme 1). Although being
insufficient in terms of yield, the addition reaction selectively
afforded (E)-b-cyanoallylborane 3 along with minor formation of
other isomers. In spite of our further trials, however, no significant
improvement of the reaction yield could be made by the modifica-
tion of the original reaction conditions. We then turned our atten-
tion to an intramolecular variant, which was found successful in
the cyanoboration of alkynes.10a
The aminocyanoboryl ether 4a was prepared by reaction of 1,1-di-
phenyl-3,4-pentadien-1-ol with cyanobis(diisopropylamino)borane.
Thecyanoborylether4aintoluenewasheatedinthepresenceofpal-
ladium or nickel catalysts bearing phosphine ligands. We found that
addition of the B–CN bond across the tethered allene moiety pro-
ceeded at 80 °C in the presence of a Pd/PMe3 catalyst (Table 1, entry
1).14 The addition took place in a regioselective fashion at the inter-
nal C@C bond to provide 5-membered allylborane 5a in 98% yield as
a sole product.15 It should be noted that some other ligands such as
tricyclohexylphosphine, triphenylphosphine, and2,20-bipyridylalso
served as effective ligands in the intramolecular cyanoboration (en-
tries 2–4). We realized that a comparable yield was attained even in
the absence of ligand (entry 5). This result may indicate that the
phosphine ligands do not have strong influence on the efficiency of
the reaction. However, we found bidentate ligands such as DPPP
by other means. Catalytic additions of boron-containing
r-bonds
to carbon–carbon multiple bonds are highly attractive, since the
reactions are not only atom-economical but also allow regio- and
stereoselective introduction of additional functionalities into the or-
ganic frameworks in one step.5–8
Our recent research interest has focused on the transition me-
tal-catalyzed carboboration reactions in which carbon–carbon
bonds are formed along with the boron–carbon bonds.9–12 We
found that the boron–cyanide bonds of cyanoboranes13 are acti-
vated by palladium or nickel complexes, leading to cyanoboration
of alkynes, which offers a unique synthetic access to b-boryl-a,b-
unsaturated nitriles with high regio- and stereoselectivities.10
These results prompted us to find a new addition reaction of
cyanoboranes to other unsaturated organic molecules. In this re-
port, we wish to describe the new synthesis of b-cyanoallylborane
derivatives by cyanoboration of allenes.
π
1) Cp( -allyl)Pd (5 mol%),
PMe3 (5 mol%)
dioxane, 130 °C
N
N
+
B
CN
Ph
•
Our study was initiated with intermolecular reactions of cyano-
boranes with terminal allenes in the presence of palladium or nick-
el catalysts. After several attempts, we found that cyanoborane 1
reacted with allene 2 at 130 °C in the presence of 5 mol % of a pal-
ladium catalyst with trimethylphosphine (5 mol %), giving allylbo-
2) pinacol
2
1
CN
Ph
O
B
O
3 (26%)
* Corresponding author. Tel.: +81 75 383 2723; fax: +81 75 383 2722.
E-mail address: suginome@sbchem.kyoto-u.ac.jp (M. Suginome).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.025

A. Yamamoto et al. / Tetrahedron Letters 50 (2009) 3168–3170
3169
Table 1
B
O
B
CN
Catalyst screening for intramolecular cyanoboration of 4aa
O
CN
iPr2N
LnPd(0)
•
NiPr2
B
Pd or Ni complex (5 mol%),
ligand (5 mol%)
B
CN
O
O
Ph
Ph
Ph
Ph
toluene, 80 °C
•
CN
oxidative
addition
reductive
elimination
5a
4a
Metal complex
Entry
Ligand
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Cp(
Cp(
Cp(
Cp(
Cp(
Cp(
Cp(
p
p
p
p
p
p
p
-allyl)Pd
-allyl)Pd
-allyl)Pd
-allyl)Pd
-allyl)Pd
-allyl)Pd
-allyl)Pd
PMe3
PCy3
PPh3
bpy
13
16
16
18
13
13
24
24
98
85
99
98
95
13
0
Ln
B
O
B
Pd
Ln
O
CN
PdCN
•
—
DPPP
P(OMe)3
PMe3
B
A
insertion
Ni(cod)2
0
a
Scheme 2. A possible mechanism of Pd-catalyzed intramolecular cyanoboration of
allenes (B: B(NiPr2)). The other mechanistic possibility in which the internal C@C
bond in A inserts into the Pd–CN bond is not shown.
A mixture of 1a (29 mg, 0.12 mmol), metal complex (6.0
mol) was heated in toluene (0.2 mL) at 80 °C.
NMR yield using dibenzyl ether as a standard.
lmol), and ligand
(6.0
l
b
intermediate A, which is formed through oxidative addition of the
B–CN bond to palladium(0) species, undergoes intramolecular
insertion of the internal C@C bond of the allenyl group. The termi-
nal C@C bond may hardly coordinate to palladium due to the
considerable ring strain. Insertion into either the B–Pd bond or the
Pd–CN bond followed by reductive elimination gives cyanobora-
tion product 5. In our mechanistic study on the alkyne cyanobora-
tion,10c the B–Pd bond was found much more prone to undergo
migratory insertion than the Pd–CN bond, although no decisive
evidence as to the mode of insertion was obtained for the present
cyanoboration of allenes.
The cyanoboration products have an allylborane substructure
with a cyano group at their b-positions, being expected to serve
as new b-cyanoallylation reagents. Since the products were not
easily isolable, one-pot, sequential cyanoboration/allylation was
attempted. The cyanoboration products 5a, 5c, and 5g in the crude
cyanoboration mixtures were reacted with benzaldehyde (Scheme
3). For instance, 5a gave homoallyl alcohol 6a in 83% overall yield
for the two steps. The allylboration step required 110 °C (6 h) to
complete. The enediol product 6a was obtained as a single isomer
with (E)-C@C bond, whose geometry was determined by nOe
experiments. Allylboranes 5c and 5g also provided enediols 6c
and 6g in 64% and 63% yields, respectively, with high stereoselec-
tivity for the (E)-isomers.
and phosphite ligands such as P(OMe)3 retarded the reaction signif-
icantly (entries 6 and 7). The combination of Ni(cod)2 and PMe3 com-
pletely failed to give the cyclization product (entry 8).
Other cyanoboryl ethers 4b–g were subjected to the cyanobora-
tion reaction in the presence of the Pd/PMe3 catalyst (Table 2).16
Cyanoboryl ethers 4b–d bearing monosubstituted allenyl groups
afforded the cyclized products 5b–d (entries 1–3). It should be
noted that the use of cyanoboryl ethers derived from tertiary alco-
hols was found to be crucial for the intramolecular cyanoboration
to proceed. Attempted reactions of cyanoboryl ethers derived from
secondary and primary alcohols resulted in no product formation.
Intramolecular cyanoboration of 4e, which carried two terminal
methyl groups at the allenyl moiety, also gave product 5e in high
yield (entry 4). In contrast, attempted cyanoboration with an alle-
nyl substrate 4f bearing a geminally disubstituted allenyl group re-
sulted in no reaction (entry 5). Cyanoboryl ether 4g derived from a
homologous allenyl alcohol gave 6-exo cyclized product 5g in good
yield (entry 6). All the cyanoboration products were found to be
thermally stable and distillable, although further purification by
silica gel chromatography was not possible due to their hydrolytic
instability.
In all cases, the intramolecular cyanoboration provided allylbor-
anes, which were formed through addition to the internal C@C
bonds of allenyl groups with C–CN bond formation at the central
carbon atoms of allenes. A possible mechanism is presumed as
follows (Scheme 2): The B–Pd bond of the borylpalladium cyanide
In summary, palladium-catalyzed cyanoboration of allenes has
been demonstrated. Although intermolecular variant was not effi-
cient, intramolecular cyanoboration of 3,4-alkadien-1-ol and 4,5-
alkadien-1-ol derivatives proceeded at their internal C@C bond,
providing b-cyanoallylboranes through 5- or 6-exo-cyclizations.
Table 2
Palladium-catalyzed intramolecular cyanoboration of 4a
iPr2N
NiPr2
π
Cp( -allyl)Pd (5 mol%),
B
CN
R3
O
B
R4
NiPr2
R3
PMe3 (5 mol%)
O
Cp(allyl)Pd (5 mol%)
O
B
R1
R4
PMe3 (5 mol%)
R1
R2
toluene
n
•
R4
R1
4a, 4c, or 4g
R2
n
CN
R1
n
toluene
R4
CN
5
4
5a, 5c, or 5g
OH
R1
Entry
4
n
R1,R2
R3
R4
Temp (°C)
Product [yield%]b
PhCHO
CN
Ph
OH
(1.5 equiv)
1
2
3
4
5
6
4b
4c
4d
4e
4f
1
1
1
1
1
2
Me, Me
Et, Et
–(CH2)4–
Me, Me
Me, Me
Me, Me
H
H
H
H
Me
H
H
H
H
Me
H
80
80
130
80
130
130
5b [80 (64)]
5c [74]
5d [49]
5e [98 (83)]
— [0]
5g [86]
R1
n
110 °C
6a (n = 1, R1 = Ph, 83%)
6c (n = 1, R1 = Et, 64%)
6g (n = 2, R1 = Me, 63%)
4g
H
a
A mixture of 4, Cp(
p-allyl)Pd (5 mol %), and PMe3 (5 mol %) was heated in
toluene.
Scheme 3. One-pot intramolecular cyanoboration/b-cyanoallylation for the syn-
thesis of diols 6.
b
NMR yield using dibenzyl ether as a standard. Isolated yield in the parentheses.

3170
A. Yamamoto et al. / Tetrahedron Letters 50 (2009) 3168–3170
13. Bu2BCN: (a) Evers, E. C.; Freitag, W. O.; Kriner, W. A.; MacDiarmid, A. G. J. Am.
Chem. Soc. 1959, 81, 5106; H2BCN: (b) Spielvogel, B. F.; Bratton, R. F.; Moreland,
C. G. J. Am. Chem. Soc. 1972, 94, 8598; Bis(dialkylamino)-cyano-boranes: (c)
Bessler, V. E.; Goubeau, J. Z. Anorg. Allg. Chem. 1967, 352, 67; (d) Meller, A.;
Maringgele, W.; Sicker, U. J. Organomet. Chem. 1977, 141, 249; (e) Suginome,
M.; Yamamoto, A.; Ito, Y. Chem. Commun. 2002, 1392.
The b-cyanoallylboranes reacted with aldehydes to give b-cyanoal-
lylation products stereoselectively.
Acknowledgments
14. One-pot intramolecular cyanoboration of 1,1-diphenyl-3,4-pentadien-1-ol
with cyanobis(diisopropylamino)borane did not afford cyanoboration
product 5a, in spite of the fact that the corresponding one-pot
intramolecular cyanoboration of alkynes was found successful as reported
previously.10a
ThisworkwassupportedbyaGrant-in-AidforScientificResearch
on Priority Areas ‘Advanced Molecular Transformations of Carbon
Resources’ from the Ministry of Education, Culture, Sports, Science,
and Technology, Japan. A.Y. thanks JSPS for the fellowship support.
15. Spectral and analytical data for the selected new compounds. Compound 5a:
1H NMR (C6D6) d 0.88 (d, J = 6.4 Hz, 3H), 1.05 (d, J = 6.4 Hz, 3H), 1.47 (d,
J = 6.8 Hz, 3H), 1.51 (d, J = 6.8 Hz, 3H), 2.15 (t, J = 8.8 Hz, 1H), 2.62–2.73 (m, 2H),
3.00 (sept, J = 6.4 Hz, 1H), 3.41 (sept, J = 6.8 Hz, 1H), 4.82 (s, 1H), 5.13 (s, 1H),
6.95–7.02 (m, 2H), 7.08–7.18 (m, 4H), 7.43–7.53 (m, 4H); 13C NMR (C6D6) d
21.9, 22.7, 24.7, 44.6, 45.9, 49.5, 88.8, 119.4, 126.25, 126.33, 126.9, 127.36,
127.41, 128.79, 128.85, 147.6, 148.2; 11B NMR (C6D6) d 33.0; HRMS (EI) Calcd
for C24H29BN2O: 372.2373; Found: 372.2377. Compound 5b: 1H NMR (C6D6) d
0.93 (d, J = 6.8 Hz, 3H), 1.04 (d, J = 6.0 Hz, 3H), 1.05 (s, 3H), 1.25 (s, 3H), 1.36 (d,
J = 6.4 Hz, 3H), 1.39 (d, J = 6.8 Hz, 3H), 1.66–1.77 (m, 2H), 2.17 (t, J = 8.8 Hz, 1H),
2.94 (sept, J = 6.4 Hz, 1H), 3.38 (sept, J = 6.8 Hz, 1H), 5.06 (s, 1H), 5.24 (s, 1H);
13C NMR (C6D6) d 22.0, 22.7, 24.1, 24.3, 30.2, 30.7, 34.0–36.5 (br), 44.5, 44.9,
49.2, 81.5, 119.5, 127.9, 128.6; 11B NMR (C6D6) d 32.1; HRMS (EI) Calcd for
C14H25BN2O: 248.2056; Found: 248.2063. Compound 5c: 1H NMR (C6D6) d 0.78
(t, J = 7.2 Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H), 0.94 (d, J = 6.8 Hz, 3H), 1.06 (d,
J = 6.8 Hz, 3H), 1.32 (q, J = 7.6 Hz, 2H), 1.36 (d, J = 6.8 Hz, 3H), 1.41 (d, J = 6.8 Hz,
3H), 1.48–1.61 (m, 2H), 1.65–1.75 (m, 2H), 2.15 (t, J = 9.6 Hz, 1H), 2.94 (sept,
J = 6.8 Hz, 1H), 3.39 (sept, J = 6.8 Hz, 1H), 5.02 (s, 1H), 5.22 (s, 1H); 13C NMR
(C6D6) d 8.9, 22.0, 22.7, 24.2, 24.3, 33.1, 33.3, 40.4, 44.4, 49.1, 86.6, 119.5, 127.5,
128.8; 11B NMR (C6D6) d 32.0; HRMS (EI) Calcd for C16H29BN2O: 276.2373;
Found: 276.2376. Compound 5e: 1H NMR (C6D6) d 0.98 (d, J = 6.8 Hz, 3H), 1.11
(s, 3H), 1.12 (d, J = 6.0 Hz, 3H), 1.38 (s, 6H), 1.42 (d, J = 6.8 Hz, 3H), 1.49 (d,
J = 6.8 Hz, 3H), 1.79 (s, 3H), 1.68–1.86 (m, 2H), 2.48 (t, J = 9.6 Hz, 1H), 3.00
(sept, J = 6.8 Hz, 1H), 3.35 (sept, J = 6.8 Hz, 1H); 13C NMR (C6D6) d 20.1, 22.1,
22.9, 24.2, 24.3, 24.7, 30.0, 31.0, 44.5, 44.7, 49.3, 81.2, 114.7, 119.7, 147.5; 11B
References and notes
1. Hall, D. G. Boronic Acids; Wiley, Weinheim: Germany, 2005.
2. (a) Miyaura, N. Top. Curr. Chem. 2002, 219, 11; (b) Suzuki, A.; Brown, H. C.. In
Organic Synthesis via Boranes; Aldrich: Milwaukee, WI, 2003; Vol. 3; (c)
Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
3. (a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16, 4229; Reviews:
(b) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169; (c) Hayashi, T.; Yamasaki,
K. Chem. Rev. 2003, 103, 2829.
4. (a) Petasis, N. A.; Akritopoulou, I. Tetrahedron Lett. 1993, 34, 583; (b) Petasis, N.
A.; Zavialov, I. A. J. Am. Chem. Soc. 1997, 119, 445.
5. For B–H bond additions, see: (a) Nöth, H.; Männig, D. Angew. Chem., Int. Ed. Engl.
1985, 24, 878; (b) Hayashi, T.; Matsumoto, Y.; Ito, Y. J. Am. Chem. Soc. 1989, 111,
3426; Review: (c) Beletskaya, I.; Pelter, A. Tetrahedron 1997, 53, 4957.
6. For B–B bond additions, see: (a) Ishiyama, T.; Nishijima, K.-i.; Miyaura, N.;
Suzuki, A. J. Am. Chem. Soc. 1993, 115, 7219; Review: (b) Ishiyama, T.; Miyaura,
N. J. Organomet. Chem. 2000, 611, 392.
7. For B–Si bond additions, see: (a) Suginome, M.; Nakamura, H.; Ito, Y. J. Chem.
Soc., Chem. Commun. 1996, 2777; (b) Suginome, M.; Ohmura, T.; Miyake, Y.;
Mitani, S.; Ito, Y.; Murakami, M. J. Am. Chem. Soc. 2003, 125, 11174; (c)
Suginome, M.; Ito, Y. J. Organomet. Chem. 2003, 680, 43. and references therein.
8. For reviews on B-element bond additions, see: (a) Beletskaya, I.; Moberg, C.
Chem. Rev. 2006, 106, 2320; (b) Suginome, M.; Matsuda, T.; Ohmura, T.; Seki, A.;
Murakami, M.. In Crabtree, R., Mingos, M., Eds.; Comprehensive Organometallic
Chemistry III; Ojima, I., Ed.; Elsevier, 2007; Vol. 10, p 725.
9. For uncatalyzed carboborations, see: Mihailov, B. M.; Bubnov, Y. N. Tetrahedron
Lett. 1971, 4597; See also: Knochel, P.. In Comprehensive Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 4, p 865.
10. Ni- and Pd-catalyzed cyanoborations: (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, A.; Sasaki, T.; Murakami, M. Organometallics 2006, 25, 2911; (d)
Ohmura, T.;Awano, T.;Suginome, M.;Yorimitsu, H.;Oshima, K. Synlett2008, 423.
11. Ni-catalyzed alkynylboration: Suginome, M.; Shirakura, M.; Yamamoto, A. J.
Am. Chem. Soc. 2006, 128, 14438.
NMR (C6D6)
d 32.7; HRMS (EI) Calcd for C16H29BN2O: 276.2373; Found:
276.2366. Compound 6a: 1H NMR (CDCl3) d 2.47 (dd, J = 4.0, 14.4 Hz, 1H), 2.83
(dd, J = 9.2, 14.4 Hz, 1H), 3.10 (dd, J = 6.0, 14.4 Hz, 1H), 3.23 (dd, J = 9.2, 14.4 Hz,
1H), 4.93 (dd, J = 3.6, 9.2 Hz, 1H), 6.35 (dd, J = 6.4, 8.8 Hz, 1H), 7.23–7.41 (m, 15
H); HRMS (CI+) Calcd for C25H22NO (MH+–H2O): 352.1701; Found: 352.1700.
Compound 6c: 1H NMR (CDCl3) d 0.86 (t, J = 7.6 Hz, 3H), 0.89 (t, J = 7.2 Hz, 3H),
1.49 (q, J = 7.2 Hz, 2H), 1.50 (q, J = 7.2 Hz, 2H), 2.18 (dd, J = 6.8, 14.8 Hz, 1H),
2.40 (dd, J = 9.2, 14.8 Hz, 1H), 2.49 (dd, J = 4.0, 14.4 Hz, 1H), 2.82 (dd, J = 9.2,
14.0 Hz, 1H), 5.00 (dd, J = 4.0, 9.2 Hz, 1H), 6.60 (dd, J = 8.4, 9.2 Hz, 1H), 7.29–
7.40 (m, 5H); HRMS (CI+) Calcd for C17H24NO2 (MH+): 274.1807; Found:
274.1816. Compound 6g: 1H NMR (CDCl3) d 1.19 (s, 6H), 1.36 (ddd, J = 5.6, 9.6,
13.6 Hz, 1H), 1.48 (ddd, J = 6.0, 9.6, 13.6 Hz, 1H), 2.06–2.16 (m, 1H), 2.21–2.32
(m, 1H), 2.54 (dd, J = 5.2, 14.4 Hz, 1H), 2.77 (dd, J = 8.0, 14.0 Hz, 1H), 4.98 (dd,
J = 5.6, 8.4 Hz, 1H), 6.46 (dd, J = 7.2, 8.0 Hz, 1H), 7.29–7.41 (m, 5H)); HRMS (CI+)
Calcd for C16H22NO2 (MH+): 260.1651; Found: 260.1650.
12. Catalytic carboborations through activation of B–Cl bond with use of
organometallic compounds as donors of organic group: (a) Suginome, M.;
Yamamoto, A.; Murakami, 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.
16. Other catalyst systems suggested as such in Table 1 including the ligandless
system (Table 1, entry 5) may be similarly used as the catalysts for the
intramolecular cyanoboration.