Radical addition of polyhaloalkanes to 2-ethynyl-4,4,5,5-tetramethyl-1,3,2- dioxaborolane

Article abstract of DOI:10.1246/bcsj.82.1433

Radical addition of bromotrichloromethane to 2- ethynyl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane takes place in the presence of a radical initiator in refluxing benzene. Perfluoroalkyl iodides undergo similar addition reactions. The addition reactions pro

Full text of DOI:10.1246/bcsj.82.1433

Short Articles
Bull. Chem. Soc. Jpn. Vol. 82, No. 11, 1433–1435 (2009) 1433
Table 1. Radical Addition of Bromotrichloromethane to 1
Radical Addition of Polyhaloalkanes
to 2-Ethynyl-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane
20 mol% initiator
3 equiv BrCCl3
O
O
O
B
H C C B
O
Cl3C
H
benzene (1.5 mL)
reflux, 4 h
1 (0.40 mmol)
Br
2 E/Z = 98:2
Entry
Initiator
Yield/%
Tatsuya Wada, Yuto Sumida, Azusa Kondoh,
Hideki Yorimitsu,* and Koichiro Oshima*
1
2
3
4
DLP
66
62
70
82a)
AIBN
ACCN
ACCN
Department of Material Chemistry, Graduate School of
Engineering, Kyoto University, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510
a) Performed for 7 h.
Received June 22, 2009
Table 2. Radical Addition of Perfluoroalkyl Iodides to 1
E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp, oshima@
orgrxn.mbox.media.kyoto-u.ac.jp
x mol% initiator
3 equiv Rf−I
O
O
O
B
H C C B
O
Rf
chlorobenzene (1.5 mL)
reflux, 1.5 h
Radical addition of bromotrichloromethane to 2-
ethynyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane takes place
in the presence of a radical initiator in refluxing benzene.
Perfluoroalkyl iodides undergo similar addition reactions.
The addition reactions proceed in an anti fashion. The
corresponding 1-halo-1-alkenylboronic esters are useful
intermediates that undergo cross-coupling reactions.
1 (0.40 mmol)
H
I
3
Entry Initiator x/mol %
Rf
3
Yield/%
1
2
3
4
5
6
7
8
9
DLP
DLP
DBP
BPO
BPO
BPO
BPO
BPO
BPO
BPO
BPO
20
20
20
20
30
C6F13
C6F13
C6F13
C6F13
C6F13
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
0a)
44
47
72
55
84
78
79
72
77
55
20 + 20b) C6F13
20 + 20b) C4F9
20 + 20b) C8F17
20 + 20b) C3F7
20 + 20b) C10F21
Radical addition of polyhaloalkanes to alkynes is an
important reaction for the synthesis of alkenyl halides.1 We
envisioned that similar radical addition to an ethynylboronic
ester would yield 1-halo-1-alkenylboronic esters, which would
serve as useful building blocks in organic synthesis.2 In the
literature,3 radical addition reactions of polyhaloalkanes to
bis(diisopropylamino)(ethynyl)borane or dibutoxy(ethynyl)-
borane have been reported. However, the starting borane and
the product were sensitive to moisture. Here we report the use
of 2-ethynyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane4 (1) as a
radical acceptor that is stable and easy to handle.
Radical addition of bromotrichloromethane to 1 proceeded
in the presence of a radical initiator in refluxing benzene
(Table 1). Thermally degradable dilauroyl peroxide (DLP),
¡,¡-azobis(isobutyronitrile) (AIBN), and ¡,¡-azobis(cyclo-
hexanecarbonitrile) (ACCN) were effective.5 Among them,
ACCN was the best initiator (Entry 3), although the difference
of the efficiency of the initiators was small. A prolonged
reaction time improved the yield of 2 (Entry 4). The reactions
yielded 2 with high regio- and stereoselectivities and were
likely to proceed in an anti fashion predominantly to yield the
E isomer with excellent selectivity (vide infra).
10
11
c)
20 + 20b) i-C3F7
a) Performed in refluxing benzene or chlorobenzene at 80 °C.
b) Performed for 3 h. See Experimental Section. c) 6 equiv of
i-C3F7I was used.
loading of BPO resulted in a lower yield of 3a (Entry 5). We
envisaged that the rate of the homolysis of BPO would be too
rapid at the high temperature and that the BPO added was
consumed within 1.5 h. We thus performed the reaction for
3 h, charging 20 mol % of BPO twice at the beginning and
after 1.5 h (Entry 6). Gratifyingly, the reaction afforded 3a in
84% yield. The regio- and stereoselectivities of the reactions
were perfect, providing 3a as a sole isomer. Other primary
perfluoroalkyl iodides reacted with 1 as smoothly as trideca-
fluorohexyl iodide (Entries 7-10). However, secondary hepta-
fluoroisopropyl iodide was less reactive, and even with a larger
amount of the starting iodide, the reaction afforded 3f in
moderate yield (Entry 11). Unfortunately, attempts to employ
tetrachloromethane and tetrabromomethane failed.
Attempted radical addition to internal alkynylboronic
esters, including phenylethynyl- and 1-octynylboronic esters,
resulted in failure. Other active organic halides such as benzyl
iodoacetate, diethyl bromomalonate, and ¡-iodo-£-butyro-
lactone were far less reactive, and virtually no reactions with
1 took place.
Radical addition of tridecafluorohexyl iodide with the aid of
DLP did not proceed in refluxing benzene or chlorobenzene
at 80 °C (Table 2, Entry 1). The reaction required an elevated
temperature as high as 132 °C (Entry 2). Di-t-butyl peroxide
(DBP) is known to be a suitable initiator at such a high
temperature.5 DBP initiated the reaction as efficiently as DLP
without significant improvement (Entry 3). Benzoyl peroxide
(BPO) proved to be more efficient (Entry 4). However, a higher
Published on the web November 10, 2009; doi:10.1246/bcsj.82.1433

1434 Bull. Chem. Soc. Jpn. Vol. 82, No. 11 (2009)
© 2009 The Chemical Society of Japan
3
tetramethylsilane as an internal standard. IR spectra were deter-
mined on a SHIMADZU FTIR-8200PC spectrometer. Elemental
analyses were carried out at the Elemental Analysis Center of
Kyoto University. Mass spectra were determined on a JEOL
MStation 700 spectrometer. TLC analyses were performed on
commercial glass plates bearing a 0.25-mm layer of Merck Silica
gel 60F254. Silica gel (Wakogel C-200) or neutral silica gel (Kanto
Chemical, silica gel 60N) was used for column chromatography.
Unless otherwise noted, materials obtained from commercial
suppliers were used without further purification. Boronic ester 1
was prepared according to the literature.4c Benzene was stored over
slices of sodium. THF was purchased from Kanto Chemical Co.,
stored under argon, and used as is. Zinc chloride was purchased
from Wako Pure Chemicals and was handled in a glove box under
argon. Tetrakis(triphenylphosphine)palladium was obtained from
Kanto Chemical Co., and stored under argon.
Rf
I
Rf
Rf
O
B
O
O
H
B
O
O
H
C C B
Rf
O
5
4
1
H
Rf
I
Z isomer of 3
Scheme 1. Rationale of regio- and stereoselectivities.
O
O
C6F13
B
C6F13
H
a)
c)
3a
H
Addition of Bromotrichloromethane.
Under argon, 2-
6 70%
ethynyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1, 61 mg, 0.40
mmol), bromotrichloromethane (0.24 g, 1.2 mmol), and ACCN
(20 mg, 0.08 mmol) were dissolved in benzene (1.5 mL) in a
reaction flask. The mixture was heated at reflux for 7 h. After the
mixture was cooled to ambient temperature, the solvent was
removed under reduced pressure. Chromatographic purification on
neutral silica gel (hexane/ethyl acetate = 30:1) by using a dry ice/
acetone-jacketed chromatographic column afforded 2 in 82% yield
(0.11 g, 0.33 mmol).
8 78%
b)
C6F13
H
3%
NOE
H
7 62%
Scheme 2. Use of 3a in cross-coupling reactions. a) 5 mol %
Pd(PPh3)4, 2 equiv PhZnCl, THF, 25 °C, 6 h; b) 10 mol %
Pd(PPh3)4, 5 equiv (Z)-1-bromopropene, 2 equiv K3PO4,
benzene/methanol = 20:1, 60 °C, 2 h; c) 10 mol %
Pd(PPh3)4, 5 equiv 4-bromotoluene, 2 equiv K2CO3,
benzene/methanol = 20:1, 60 °C, 21 h.
Addition of Perfluoroalkyl Iodide. Under argon, 2-ethynyl-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1, 61 mg, 0.40 mmol),
tridecafluorohexyl iodide (0.54 g, 1.2 mmol), and BPO (19 mg,
0.08 mmol) were dissolved in chlorobenzene (1.5 mL) in a reaction
flask. The mixture was heated at reflux for 1.5 h. After the mixture
was cooled to room temperature, an additional BPO (19 mg,
0.08 mmol) was added. The mixture was stirred at reflux for an
additional 1.5 h. The solvent was removed under reduced pressure.
Chromatographic purification on neutral silica gel (hexane/ethyl
acetate = 30:1) by using a dry ice/acetone-jacketed chromato-
graphic column afforded 2 in 84% yield (0.20 g, 0.34 mmol).
The regio- and stereoselectivity are controlled according
to the conventional rules for radical addition reactions
(Scheme 1).3a,6 The radical addition of polyhaloalkyl radical
to 1 occurs at the less hindered terminal carbon. The sub-
sequent halogen abstraction proceeds mainly from radical 4
since polyhaloalkyl iodide could approach 4 more efficiently
than it does radical 5.
The products are useful intermediates that undergo
cross-coupling reactions. For instance, treatment of 3a with
phenylzinc chloride under palladium catalysis afforded the
corresponding ¡-borylstyrene derivative 6 in good yield
(Scheme 2).7 Alkenylboron compound 6 reacted with (Z)-1-
bromopropene or 4-bromotoluene in the presence of a base and
a catalytic amount of tetrakis(triphenylphosphine)palladium to
provide the corresponding cross-coupling product 7 or 8 in
good yield.8 The NOE analysis of 7 verified the stereo-
chemistry of 3 as well as 7 itself, given that the sequential
cross-coupling reactions proceeded with retention of config-
uration.9
Cross-Coupling Reaction of 3a.
Phenyllithium in cyclo-
hexane-diethyl ether (1.09 M, 1.8 mL, 2.0 mmol) was added to a
solution of zinc chloride (0.33 g, 2.40 mmol) in THF (3.5 mL)
at 0 °C under argon. The mixture was stirred for 15 min at room
temperature. The phenylzinc reagent prepared above was then
added to a solution of 3a (0.60 g, 1.00 mmol) and Pd(PPh3)4
(58 mg, 0.05 mmol) in THF (0.5 mL) at 0 °C under argon. The
mixture was stirred at room temperature for 6 h. The reaction was
quenched with aqueous ammonium chloride solution and extracted
with ethyl acetate. After removal of the solvent, the residue was
chromatographed (eluted with hexane/ethyl acetate = 20:1) on
neutral silica gel to give 6 in 70% yield (0.38 g, 0.70 mmol).
Cross-Coupling Reaction of 6.
Under argon, 6 (0.11 g,
0.20 mmol), 4-bromotoluene (0.17 g, 1.00 mmol), potassium car-
bonate (55 mg, 0.40 mmol), and Pd(PPh3)4 (23 mg, 0.02 mmol)
were dissolved in benzene (2.0 mL) and methanol (0.1 mL) in a
reaction flask. The mixture was heated at 60 °C for 21 h. The
reaction was quenched with water, and the product was extracted
with ethyl acetate. After the solvent was removed, the residue was
chromatographed (eluted with hexane) on silica gel to afford 8 in
78% yield (80 mg, 0.16 mmol).
In summary, 2-ethynyl-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane serves as a good radical acceptor in radical addition
reactions of polyhaloalkanes. The adducts are useful inter-
mediates for the synthesis of multisubstituted alkenes.
Experimental
(E)-2-(1-Bromo-3,3,3-trichloro-1-propenyl)-4,4,5,5-tetrameth-
yl-1,3,2-dioxaborolane (2): IR (neat): 2984, 1635, 1496, 1384,
Instrumentation and Chemicals. 1H NMR (500 MHz) and
13C NMR (126 MHz) spectra were taken on a Varian UNITY
INOVA 500 spectrometer and were obtained in CDCl3 with
1
1240, 854, 700 cm¹1; H NMR (CDCl3): ¤ 1.31 (s, 12H), 7.05 (s,
1H); 13C NMR (CDCl3): ¤ 24.31, 85.19, 93.17, 144.00. HRMS

T. Wada et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 11 (2009) 1435
(FAB): Found: 348.9345 [(M + H)+]; Calcd for C9H1411B79Br-
35Cl3O2: 348.9336.
¤ 15.30, 113.71 (t, J = 22.0 Hz), 125.09, 127.29, 128.66, 129.16,
132.28, 139.98, 150.40. HRMS (EI): Found: 462.0660; Calcd for
C17H11F13: 462.0653.
(E)-2-(3,3,4,4,5,5,6,6,7,7,8,8,8-Tridecafluoro-1-iodo-1-octenyl)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3a): IR (neat): 2984,
(Z)-3,3,4,4,5,5,6,6,7,7,8,8,8-Tridecafluoro-1-(4-methylphenyl)-
1-phenyl-1-octene (8): IR (neat): 3030, 1635, 1448, 1240, 1202,
1
1683, 1652, 1363, 1241, 1145, 850, 709 cm¹1; H NMR (CDCl3):
¤ 1.29 (s, 12H), 6.84 (t, J = 12.5 Hz, 1H); 13C NMR (CDCl3):
¤ 24.06, 85.27, 134.80 (t, J = 22.9 Hz). HRMS (EI): Found:
597.9853; Calcd for C14H1311BF13IO2: 597.9846.
1052, 824 cm¹1; H NMR (CDCl3): ¤ 2.40 (s, 3H), 6.06 (t, J =
1
15.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H),
7.23-7.28 (m, 2H), 7.31-7.40 (m, 3H); 13C NMR (CDCl3): ¤
21.28, 112.46 (t, J = 20.6 Hz), 127.99, 128.44, 128.55, 129.00,
129.41, 134.55, 138.24, 141.07, 154.56; Anal. Found: C, 49.05; H,
2.80%. Calcd for C21H13F13: C, 49.23; H, 2.56%.
(E)-2-(3,3,4,4,5,5,6,6,6-Nonafluoro-1-iodo-1-hexenyl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (3b): IR (neat): 2985, 1636,
1
1368, 1236, 1135, 850, 746 cm¹1; H NMR (CDCl3): ¤ 1.30 (s,
12H), 6.84 (t, J = 12.5 Hz, 1H); 13C NMR (CDCl3): ¤ 24.12,
85.29, 134.72 (t, J = 22.5 Hz). HRMS (FAB): Found: 498.0015
[(M + H)+]; Calcd for C12H1410BF9IO2: 498.9988.
The work is supported by Grants-in-Aid for Scientific
Research and GCOE Research. Y.S. and A.K. acknowledge
JSPS for financial support.
(E)-2-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Heptadecafluoro-1-
iodo-1-decenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3c):
IR (neat): 2985, 1640, 1384, 1368, 1343, 1243, 1212, 1147, 966,
852 cm¹1; 1H NMR (CDCl3): ¤ 1.30 (s, 12H), 6.85 (t, J = 12.5 Hz,
1H); 13C NMR (CDCl3): ¤ 24.12, 85.29, 134.84 (t, J = 22.4 Hz).
HRMS (FAB): Found: 698.9842 [M]; Calcd for C16H1311BF17IO2:
698.9860.
References
1
a) M. P. Jennings, E. A. Cork, P. V. Ramachandran, J. Org.
Chem. 2000, 65, 8763. b) Y. Takeyama, Y. Ichinose, K. Oshima,
K. Utimoto, Tetrahedron Lett. 1989, 30, 3159. c) M. S. Kharasch,
J. J. Jerome, W. H. Urry, J. Org. Chem. 1950, 15, 966. d) K. Baum,
C. D. Bedford, R. J. Hunadi, J. Org. Chem. 1982, 47, 2251.
e) N. O. Brace, J. E. Van Elswyk, J. Org. Chem. 1976, 41, 766.
(E)-2-(3,3,4,4,5,5,5-Heptafluoro-1-iodo-1-pentenyl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (3d): IR (neat): 2985, 1639,
¹1
1383, 1367, 1351, 1229, 1178, 1142, 1118, 965, 851 cm
;
1H NMR (CDCl3): ¤ 1.30 (s, 12H), 6.84 (t, J = 12.5 Hz, 1H);
13C NMR (CDCl3): ¤ 24.13, 85.29, 134.60 (t, J = 23.0 Hz). HRMS
(FAB): Found: 447.9955; Calcd for C11H1311BF7IO2: 447.9942.
(E)-2-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-Hen-
icosafluoro-1-iodo-1-dodecenyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
2
a) H. C. Brown, T. Imai, N. G. Bhat, J. Org. Chem. 1986,
51, 5277. b) J. R. Waas, A. Sidduri, P. Knochel, Tetrahedron Lett.
1992, 33, 3717. c) T. Moriya, N. Miyaura, A. Suzuki, Chem. Lett.
1993, 1429.
3
a) F. Lhermitte, B. Carboni, Synlett 1996, 377. b) D. S.
Matteson, K. Peacock, J. Org. Chem. 1963, 28, 369.
a) M. W. Davies, C. N. Johnson, J. P. A. Harrity, J. Org.
borolane (3e): IR (nujol): 2953, 1635, 1376, 1366, 1339, 1243,
¹1
1151, 1141, 1117, 965, 846 cm
;
1H NMR (CDCl3): ¤ 1.30 (s,
4
12H), 6.85 (t, J = 12.5 Hz, 1H); 13C NMR (CDCl3): ¤ 24.11,
85.28, 134.84 (t, J = 23.4 Hz); Anal. Found: C, 27.22; H, 1.36%.
Calcd for C18H13BF21IO2: C, 27.09; H, 1.64%.
Chem. 2001, 66, 3525. b) A. Geny, D. Lebœuf, G. Rouquié,
K. P. C. Vollhardt, M. Malacria, V. Gandon, C. Aubert,
Chem.®Eur. J. 2007, 13, 5408. c) Y. Yamamoto, K. Hattori,
J. Ishii, H. Nishiyama, Tetrahedron 2006, 62, 4294.
(E)-2-(3,4,4,4-Tetrafluoro-1-iodo-3-trifluoromethyl-1-buten-
yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3f):
IR (neat):
5
Ten hour half-life temperatures: DLP, 62 °C; AIBN, 65 °C;
BPO, 74 °C; ACCN, 88 °C; DBP, 124 °C.
a) B. Kopping, C. Chatgilialoglu, M. Zehnder, B. Giese,
2984, 1652, 1637, 1473, 1374, 1302, 1228, 983 cm¹1; H NMR
(CDCl3): ¤ 1.30 (s, 12H), 6.74 (d, J = 22.0 Hz, 1H); 13C NMR
(CDCl3): ¤ 24.10, 85.13, 131.41 (d, J = 15.3 Hz). HRMS (FAB):
Found: 446.9965; Calcd for C11H1310BF7IO2: 446.9978.
1
6
J. Org. Chem. 1992, 57, 3994. b) B. Giese, Angew. Chem., Int. Ed.
Engl. 1989, 28, 969.
(E)-2-(3,3,4,4,5,5,6,6,7,7,8,8,8-Tridecafluoro-1-phenyl-1-octe-
7
The use of an excess amount of organozinc reagents is not a
special case. For instance, see reference 2c.
The reason for the necessity of the excess organic halides is
not clear. The reaction with 3 equiv of (Z)-1-bromopropene or 4-
bromotoluene provided 7 or 8 in 42% or 53% yield, respectively.
nyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6):
IR (neat):
2984, 1496, 1412, 1112, 971, 854, 700 cm¹1; H NMR (CDCl3):
¤ 1.33 (s, 12H), 6.13 (t, J = 14.0 Hz, 1H), 7.33-7.43 (m, 5H);
13C NMR (CDCl3): ¤ 24.65, 84.80, 122.42 (t, J = 22.0 Hz),
126.84, 128.84, 128.92, 138.74. Anal. Found: C, 43.60; H,
3.25%. Calcd for C20H18BF13O2: C, 43.82; H, 3.31%.
8
1
9
a) N. Miyaura, M. Satoh, A. Suzuki, Tetrahedron Lett.
1986, 27, 3745. b) J.-M. Duffault, J. Einhorn, A. Alexakis,
Tetrahedron Lett. 1991, 32, 3701. c) S. Huo, E. Negishi, in
Handbook of Organopalladium Chemistry for Organic Synthesis,
ed. by E. Negishi, John Wiley & Sons, New York, 2002, Vol. 1,
Chap. III.2.6.
(2Z,4E)-6,6,7,7,8,8,9,9,10,10,11,11,11-Tridecafluoro-4-phenyl-
2,4-undecadiene (7): IR (neat): 3034, 1642, 1609, 1448, 1364,
1
1201, 1144, 848 cm¹1; H NMR (CDCl3): ¤ 1.37 (d, J = 7.5 Hz,
3H), 5.80 (t, J = 15.0 Hz, 1H), 5.92 (dq, J = 11.5, 7.5 Hz, 1H),
6.41 (d, J = 11.5 Hz, 1H), 7.35-7.45 (m, 5H); 13C NMR (CDCl3):