Stereoselective synthesis of (E)- and (Z)-fluoroalkenylboronates using 2-fluoroalkylideneiodonium ylides generated from (2-fluoro-1-alkenyl)iodonium salts

Article abstract of DOI:10.1021/jo701784t

(Chemical Equation Presented) (E)- and (Z)-(fluoroalkenyl)boronates were prepared stereospecifically by the reaction of 2-fluoroalkylideneiodonium ylide generated from (E)- or (Z)-(2-fluoroalkenyl)iodonium salts with di(p-fluorophenoxy)-alkylboranes, foll

Full text of DOI:10.1021/jo701784t

Stereoselective Synthesis of (E)- and (Z)-Fluoroalkenylboronates
Using 2-Fluoroalkylideneiodonium Ylides Generated from
(2-Fluoro-1-alkenyl)iodonium Salts
Tong Guan, Masanori Yoshida, and Shoji Hara*
Graduate School of Engineering, Hokkaido UniVersity, Sapporo 060-8628, Japan
shara@eng.hokudai.ac.jp
ReceiVed August 15, 2007
(E)- and (Z)-(fluoroalkenyl)boronates were prepared stereospecifically by the reaction of 2-fluoroalky-
lideneiodonium ylide generated from (E)- or (Z)-(2-fluoroalkenyl)iodonium salts with di(p-fluorophenoxy)-
alkylboranes, followed by transesterification to pinacol esters. The resulting pinacol esters of
(fluoroalkenyl)boranes were used for the stereoselective synthesis of trisubstituted fluoroalkenes by cross-
coupling reactions.
Introduction
difluoroalkenyl)metals,4 have been used as versatile building
blocks for fluoroalkene synthesis by cross-coupling reactions,5
(2-fluoroalkenyl)metals have not been used for the cross-
coupling reactions. Recently, we reported the stereoselective
synthesis of (E)- and (Z)-(2-fluoroalkenyl)iodonium salts (1)6
and their use for the synthesis of various fluoroalkenes by cross-
coupling reactions.7 Quite recently, we succeeded in generation
of 2-fluoroalkylideneiodonium ylides from 1 and their use for
the stereoselective synthesis of (E)- and (Z)-dialkyl(2-fluoro-
alkenyl)boranes (2a) by the reaction with trialkylboranes
(Scheme 1).8 Though R-hydrogen of alkenyliodonium salts is
known to be acidic and is readily abstracted by base, the
generated iodonium ylide is unstable and decomposes to a
carbene species quickly.9 By treatment of 1 with LDA in the
presence of trialkylborane, the generated iodonium ylide made
a borate complex with trialkylborane before decomposition to
the carbene. Migration of an alkyl group from the boron to
R-carbon with inversion of sp2 carbon took place as in the
Transition metal-catalyzed cross-coupling reactions of alk-
enylmetals with aryl or alkenyl halides have been successfully
used for the stereoselective synthesis of alkenes with various
functional groups.1 Although (fluoroalkenyl)metals, such as (1-
fluoroalkenyl)metals,2 (1,2-difluoroalkenyl)metals,3 and (2,2-
(1) (a) Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: Weinheim, 1999. (b) Cross-Coupling Reactions;
Miyaura, N., Ed.; Springer: Berlin, 2002.
(2) Sn: (a) Matthews, D. P.; Waid, P. P.; Sabol, J. S.; McCarthy, J. R.
Tetrahedron Lett. 1994, 35, 5177. (b) Chen, C.; Wilcoxen, K.; Kim, K.;
McCarthy, J. R. Tetrahedron Lett. 1997, 38, 7677. (c) Andre`s, D. F.;
Laurent, E. G.; Marquet, B. S. J. Fluorine Chem. 1998, 92, 63. (d) Chen,
C.; Wilcoxen, K.; Zhu, Y.-F.; Kim, K.; McCarthy, J. R. J. Org. Chem.
1999, 64, 3476. (e) Sciotti, R. J.; Pliushchev, M.; Wiedeman, P. E.; Balli,
D.; Flamm, R.; Nilius, A. M.; Marsh, K.; Stolarik, D.; Jolly, R.; Ulrich, R.;
Djuric, S. W. Bioorg. Med. Chem. Lett. 2002, 12, 2121. (f) Gernert, D. L.;
Ajamie, R.; Ardecky, R. A.; Bell, M. G.; Leibowitz, M. D.; Mais, D. A.;
Mapes, C. M.; Michellys, P. Y.; Rungta, D.; Reifel-Miller, A.; Tyhonas, J.
S.; Yumibe, N.; Grese, T. A. Bioorg. Med. Chem. Lett. 2003, 13, 3191. (g)
Berkowitz, D. B.; Salud-Bea, R.; Jahng, W.-J. Org. Lett. 2004, 6, 1821. Si:
Hanamoto, T.; Kobayashi, T. J. Org. Chem. 2003, 68, 6354. Ge: Wang,
Z.; Gonzalez, A.; Wnuk, S. F. Tetrahedron Lett. 2005, 46, 5313.
(3) (a) Lu, L.; Burton, D. J. Tetrahedron Lett. 1997, 38, 7673. (b) Liu,
Q.; Burton, D. J. Org. Lett. 2002, 4, 1483. (c) Wang, Y.; Burton, D. J.
Org. Lett. 2006, 8, 1109.
(6) (E)-isomer: (a) Hara, S.; Yoshida, M.; Fukuhara, T.; Yoneda, N.
Chem. Commun. 1998, 965. (b) Yoshida, M.; Kawakami, K.; Hara, S.
Synthesis 2004, 2821. (Z)-isomer: (c) Yoshida, M.; Hara, S. Org. Lett. 2003,
5, 573. (d) Yoshida, M.; Osafune, K.; Hara, S. Synthesis 2007, 1542.
(7) (a) Hara, S.; Yamamoto, K.; Yoshida, M.; Fukuhara, T.; Yoneda, N.
Tetrahedron Lett. 1999, 40, 7815. (b) Yoshida, M.; Hara, S.; Fukuhara, T.;
Yoneda, N. Tetrahedron Lett. 2000, 41, 3887. (c) Yoshida, M.; Nagahara,
D.; Fukuhara, T.; Yoneda, N.; Hara, S. J. Chem. Soc., Perkin Trans. 1 2001,
2283. (d) Yoshida, M.; Komata, A.; Hara, S. J. Fluorine Chem. 2004, 125,
527. (e) Yoshida, M.; Komata, A.; Hara, S. Tetrahedron 2006, 62, 8636.
(8) Hara, S.; Guan, T.; Yoshida, M. Org. Lett. 2006, 8, 2639.
(4) Ichikawa, J. J. Fluorine Chem. 2000, 105, 257 and references cited
therein.
(5) (Fluoroalkadienyl)metals were also used for the fluoropolyene
synthesis by application to the cross-doupling reactions; see: (a) Shinada,
T.; Sekiya, N.; Bojkova, N.; Yoshihara, K. Synlett 1995, 1247. (b)
Tsuchikawa, H.; Matsushita, N.; Matsumori, N.; Murata, M.; Oishi, T.
Tetrahedron Lett. 2006, 47, 6187. (c) Sakai, M.; Guan, T; Hara, S. J.
Fluorine Chem. 2007, 128, in press.
(9) (a) Kitamura, T.; Stang, P. J. Tetrahedron Lett. 1988, 29, 1887. (b)
Ochiai, M.; Takaoka, Y.; Nagao, Y. J. Am. Chem. Soc. 1988, 110, 6565.
10.1021/jo701784t CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/03/2007
J. Org. Chem. 2007, 72, 9617-9621
9617

Guan et al.
SCHEME 1
SCHEME 2
TABLE 1. Reaction of Alkylideneiodonium Ylide with Various
Hexylboronatesa
SCHEME 3
noxyborane gave 3 in 57% and 70% yields, respectively (entries
3 and 6). The best result was obtained using di(p-fluorophe-
noxy)hexylborane, which gave 3 in 82% yield (entry 7).
Di(p-fluorophenoxy)(8-fluoro-7-octadecenyl)borane, prepared
by the reaction of 1a with di(p-fluorophenoxy)hexylborane, is
moisture sensitive, and its purification by silica gel column
chromatography is difficult. Therefore, we converted it to the
stable pinacolborane derivative by transesterification12 and (E)-
2-(8-fluorooctadec-7-en-7-yl)-4,4,5,5-tetramethyl[1,3,2]-
dioxaborolane (4a) was obtained in 72% yield after purification
by column chromatography. The (Z)-isomer (4b) was also
obtained in 50% yield from the (E)-2-fluorododecen-1-yliodo-
nium salt (1b)6 in a similar manner. The yield of 4b was lower
than that of 4a because of the instability of 4b.8 The stereo-
chemistry of 4a and 4b was determined by two methods:
observation of NOE in their 1H NMR spectra and their
conversion to (Z)- and (E)-trisubstituted fluoroalkenes (5a and
5b). In 1H NMR of (E)-isomer 4a, NOE interaction was
observed between the protons attached to the allylic carbons.
On the other hand, the NOE interaction of the allylic protons
was not observed in (Z)-isomer 4b (Scheme 2).
By the Suzuki-Miyaura coupling reaction with iodobenzene,
4a and 4b were converted to (Z)- and (E)-7-phenyl-8-fluorooc-
tadec-7-ene (5a) and (5b), respectively,1b and their spectra data
were in good agreement with the previously reported data
(Scheme 3).8 These results support the (E)- and (Z)-stereochem-
istry of 4a and 4b.
From various (fluoroalkenyl)iodonium salts (1a-f), corre-
sponding (fluoroalkenyl)boronates (4a-h) were obtained ste-
reoselectively (Table 2). (Fluoroalkenyl)iodonium salts with
functional groups such as acetate (1c), benzyl ether (1d), ester
(1e), and acetal (1f) can be prepared from corresponding
a 1.5 equiv of LDA and the boronate to 1a were used. b Isolated yield
based on 1a.
reaction of R-haloalkenylborates to give 2a stereoselectively.10
However, the resulting dialkyl(2-fluoroalkenyl)borane 2a is not
stable enough to isolate by column chromatography, and we
converted it to 2-fluoroalkene, 1-iodo-2-fluoroalkene, and
R-fluoroketone without isolation.8 (2-Fluoroalkenyl)boronate
(2b) is more stable than 2a and suitable for isolation. In
particular, a pinacol ester is highly stable and can be purified
by silica gel column chromatography.11 Therefore, we examined
the reaction of the iodonium ylide with various alkylboronate
derivatives for the preparation of 2b (Scheme 1).
Results and Discussion
Synthesis of (Fluoroalkenyl)boronates. We applied hexyl-
boronate derivatives of various alcohols and phenols to the
reaction with the iodonium ylide generated from the (Z)-2-
fluorododecen-1-yliodonium salt (1a),7 and the yield was
obtained after converting the product 2b to 8-fluorooctadecan-
7-one (3) by oxidation (Table 1). The boronate derivatives of
aliphatic alcohols are less reactive than that of phenols, and 3
was obtained only in poor yield (<10%) (entries 1, 2, 4, and
5). On the other hand, B-hexylcatecholborane and hexyldiphe-
(10) (a) Organic Synthesis Via Boranes; Brown, H. C., Ed.; Wiley-
Interscience: New York, 1975. (b) Hata, T.; Kitagawa, H.; Masai, H.;
Kurahashi, T.; Shimizu, M.; Hiyama, T. Angew. Chem., Int. Ed. 2001, 40,
790.
(11) Pandya, S. U.; Pinet, S.; Chavant, P. Y.; Valle´e, Y. Eur. J. Org.
Chem. 2003, 3621.
(12) (a) Vaultier, M.; Truchet, F.; Carboni, B.; Hoffmann, R. W.; Denne,
I. Tetrahedron Lett. 1987, 28, 4169. (b) Fresneda, P. M.; Vaultier, M.
Tetrahedron Lett. 1989, 30, 2929. (c) Marko´, I. E.; Giard, T.; Sumida, S.;
Gies, A.-E. Tetrahedron Lett. 2002, 43, 2317. (d) Roy, C. D.; Brown, H.
C. J. Organomet. Chem. 2007, 692, 784.
9618 J. Org. Chem., Vol. 72, No. 25, 2007

StereoselectiVe Synthesis of (E)- and (Z)-Fluoroalkenylboronates
TABLE 2. Stereoselective Synthesis of (2-Fluoroalkenyl)boronatesa
TABLE 3. Stereoselective Synthesis of Trisubstituted
Fluoroalkenes by the Cross-Coupling Reaction of
(Fluoroalkenyl)boronates with Aryl or Alkenyl Halidesa
a 1.5 equiv of LDA and R-B(OC6H4-F-p)2 to 1 were used. b Isolated
yield based on 1 used.
a 5 mol % of Pd(PPh3)4, 2 equiv of KOH in EtOH, and 1.2 equiv of
halide to 4 were used. b Isolated yield based on 4 used. c 2 equiv of K3PO4
in H2O was used instead of KOH.
alkynes,6 and the corresponding functionalized (fluoroalkenyl)-
boronates (4c-f) can be prepared from them. Introduction of
the functional groups into 4 using the functionalized alkylbo-
ronates is also possible. Using di(p-fluorophenoxy)(3-bromopro-
pyl)borane, the (1-bromo-5-fluoropentadecan-4-en-4-yl)boronate
(4h) was obtained. An alkenylboronate can be also used for
the reaction: for example, from di(p-fluorophenoxy)hex-1-en-
1-ylborane, (8-fluorooctadeca-5,7-dien-7-yl)boronate (4g) was
obtained stereoselectively.
Summary
We succeeded in the stereoselective synthesis of (fluoroalk-
enyl)boronates by the reaction of alkylideneiodonium ylide
generated from (fluoroalkenyl)iodonium salts with di(p-fluo-
rophenoxy)alkylborane. The (fluoroalkenyl)boronates were iso-
lated as stable pinacol esters. Starting from (E)- or (Z)-
fluoroalkenyliodonium salts, (E)- or (Z)-(fluoroalkenyl)boronates
can be prepared stereoselectively. Various functional groups can
be introduced into the (fluoroalkenyl)boronates using function-
alized (fluoroalkenyl)iodonium salts or functionalized alkylbo-
ronates. The resulting (E)- and (Z)-(fluoroalkenyl)boronates can
be used in a cross-coupling reaction with aryl or alkenyl halides
for the synthesis of trisubstituted fluoroalkenes.
Application of (Fluoroalkenyl)boronates in the Suzuki-
Miyaura Coupling Reaction. The resulting (fluoroalkenyl)-
boronates were used in the Suzuki-Miyaura coupling reaction
for the synthesis of polyfunctionalized trisubstituted fluoroalk-
enes (Table 3).1b The cross-coupling reactions with aryl halides
or alkenyl halides proceeded stereospecifically, and from (E)-
(fluoroalkenyl)boronates (4a,e-g), arylated (Z)-fluoroalkenes
(5a, 6, 8) or fluoroalkadienes (7, 9, 10) were obtained. On the
other hand, from (Z)-isomer (4b), (E)-fluoroalkene (5b) was
selectively formed. The functional groups such as ester, acetal
can tolerate the reaction conditions, and corresponding poly-
functionalized arylated fluoroalkene (8) or fluoroalkadiene (9)
was obtained stereoselectively. Though we did not optimized
the conditions of the cross-coupling well, lower reaction
temperature (80-85 °C) is preferable for the functionalized
fluoroalkene synthesis.
Experimental Section
1. General Methods. The IR spectra were recorded using an
FT/IR-410 spectrophotometer. The H NMR (400 MHz) spectra,
1
13C NMR (100 MHz), 19F NMR (376 MHz), and 11B NMR (128
MHz) spectra were recorded in CDCl3 on an FT NMR spectrometer,
and the chemical shifts, δ, are referred to TMS (1H and 13C), CFCl3
(19F), and BF3 etherate (11B), respectively. The EI-high-resolution
mass spectra were measured on a spectrometer. HBBr2-SMe2 and
p-fluorophenol were purchased from a commercial. (E)-(2-Fluo-
rododec-1-enyl)iodonium salt (1b) and (Z)-2-fluoroalk-1-enyliodo-
nium salts (1a,c-f) were prepared from the corresponding 1-alkynes
according to the literatures.6
J. Org. Chem, Vol. 72, No. 25, 2007 9619

Guan et al.
Preparation of Di(p-fluorophenoxy)hexylborane. In a 100 mL
flask fitted with a reflux condenser were placed 1-hexene (1.68
mg, 20 mmol) and CH2Cl2 (15 mL). After the addition of a 1 M
CH2Cl2 solution of HBBr2-SMe2 (20 mL, 20 mmol) at room
temperature, the mixture was stirred under reflux for 3 h. The
reaction mixture was cooled to 0 °C, and p-fluorophenol (4.48 g,
40 mmol) in diethyl ether (10 mL) was added. The mixture was
stirred at 0 °C for 30 min, and then MeOH (1.28 g, 40 mmol) was
added. The mixture was stirred for 10 min and the solvent was
removed under reduced pressure. Distillation of the residue under
reduced pressure gave di(p-fluorophenoxy)hexylborane as a clear
liquid (bp 140-145 °C/0.3 mmHg).
1JC-F ) 272.4 Hz); 11B NMR (128 MHz, CDCl3) δ 31.6 (s); HRMS
(EI) calcd for C24H46FO2B 396.3575, found 396.3586
(E)-2-(17-Acetoxy-8-fluoroheptadec-7-en-7-yl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (4c): IR (neat) 2930, 2857, 1741,
1
1661, 1467, 1146 cm-1; H NMR (CDCl3, 400 MHz) δ 0.88 (t, J
) 6.9 Hz, 3H), 1.28-1.65 (m, 22H), 1.28 (s, 12 H), 2.00 (t, J )
7.3 Hz, 2H), 2.05 (s, 3H), 2.26 (dt, J ) 23.3, 8.2 Hz, 2H), 4.05 (t,
J ) 6.8 Hz, 2H); 19F NMR (CDCl3, 376 MHz) δ -85.24 to -85.11
(m, 1F); 13C NMR (CDCl3, 100 MHz) δ 14.07, 21.00, 22.59, 24.70
2
(4C), 25.86, 26.38, 28.09, 28.19, 28.54, 29.13 (d, JC-F ) 27.1
3
Hz), 29.19 (2C), 29.28, 29.32, 30.58 (d, JC-F ) 2.9 Hz), 31.73,
1
64.61, 82.95 (2C), 169.01 (d, JC-F ) 257.1 Hz), 171.22; HRMS
(EI) calcd for C25H46FO4B 440.3473, found 440.3469.
Preparation of 8-Fluoro-7-octadecanone (3). General Proce-
dure for the Reaction of 1a with Hexylboronates. To a THF
solution (2.5 mL) of 1a (238 mg, 0.5 mmol) was added at -78 °C
a 1 M THF solution (0.75 mL) of hexylboronate (0.75 mmol) and
LDA (0.75 mmol), prepared by the addition of a hexane solution
of BuLi (0.47 mL of a 1.6 M solution, 0.75 mmol) to diisopropy-
lamine (76 mg, 0.75 mmol) in THF (5 mL). The mixture was stirred
at -40 °C for 3 h and at room temperature for 1 h. Then the mixture
was cooled to 0 °C, and 30% aq H2O2 (10 mL) was added. After
being stirred at room temperature for 2 h, the mixture was poured
into water and extracted with ether three times. The combined
organic layer was dried over MgSO4 and concentrated under
reduced pressure. Purification by column chromatography (silica
gel/hexane-ether gradient) gave 3: IR (neat) 2926, 2855, 1725, 1466
(E)-2-(1-Benzyloxy-4-fluoroundec-4-en-5-yl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (4d): IR (neat) 2929, 2857, 1663, 1145
1
cm-1; H NMR (CDCl3, 400 MHz) δ 0.87 (t, J ) 7.0 Hz, 3H),
1.26-1.28 (m, 8 H), 1.28 (s, 12 H), 1.85 (q, J ) 6.8 Hz, 2H), 2.02
(t, J ) 7.6 Hz, 2H), 2.41 (dt, J ) 23.0, 7.6 Hz, 2H), 3.50 (t, J )
6.2 Hz, 2H), 4.49 (s, 2 H), 7.27-7.34 (m, 5H); 19F NMR (CDCl3,
376 MHz) δ -85.96 to -85.82 (m, 1F); 13C NMR (CDCl3, 100
MHz) δ 14.03, 22.54, 24.66 (4C), 25.79 (d, 2JC-F ) 30.4 Hz), 26.36,
28.07 (d, 3JC-F ) 9.9 Hz), 28.97, 30.52 (d, 3JC-F ) 2.7 Hz), 31.69,
69.18, 72.75, 82.95 (2C), 127.43, 127.51 (2C), 128.26 (2C), 138.40,
1
168.14 (d, JC-F ) 256.9 Hz); HRMS (EI) calcd for C24H38FO3B
404.2898, found 404.2897.
Benzyl (E)-5-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)dodec-5-enoate (4e): IR (neat) 3034, 2858, 1739, 1661, 1456,
1
cm-1; H NMR (400 MHz, CDCl3) δ 0.86-0.90 (m, 6H), 1.26-
1
1144 cm-1; H NMR (CDCl3, 400 MHz) δ 0.87 (t, J ) 7.0 Hz,
1.60 (m, 24H), 1.69-1.86 (m, 2H), 2.50-2.66 (m, 2H), 4.72 (ddd,
J ) 50.4, 7.9, 4.2 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ -192.60
to -192.31 (m, 1F); 13C NMR (100 MHz, CDCl3) δ 14.00, 14.09,
22.47, 22.62, 22.67, 24.52 (d, 3JC-F ) 2.9 Hz), 28.82, 29.17, 29.29,
29.33, 29.49, 29.54, 31.55, 31.88, 32.06 (d, 2JC-F ) 20.7 Hz), 38.02,
96.07 (d, 1JC-F ) 183.6 Hz), 210.49 (d, 2JC-F ) 24.6 Hz); HRMS
(EI) calcd for C18H35OF 286.2672, found 286.2671.
3H), 1.25-1.27 (m, 8 H), 1.27 (s, 12 H), 1.89 (q, J ) 7.5 Hz, 2H),
1.97 (t, J ) 7.4 Hz, 2H), 2.34 (dt, J ) 22.7, 7.5 Hz, 2H), 2.41 (t,
J ) 7.5 Hz, 2H), 5.11 (s, 2 H), 7.32-7.37 (m, 5 H); 19F NMR
(CDCl3, 376 MHz) δ -86.14 to -86.01 (m, 1F); 13C NMR (CDCl3,
100 MHz) δ 14.07, 21.55, 22.58, 24.70 (4C), 28.08, 28.28 (d, 2JC-F
) 22.1 Hz), 28.98, 30.48, 30.51, 31.72, 33.34, 66.19, 83.06 (2C),
1
128.20 (2C), 128.53 (2C), 135.91, 167.35 (d, JC-F ) 256.9 Hz),
(E)-2-(8-Fluorooctadec-7-en-7-yl)-4,4,5,5-tetramethyl-1,3,2-di-
oxaborolane (4a). General Procedure for (2-Fluoroalkenyl)-
boronate. To a THF solution (2.5 mL) of 1a (238 mg, 0.5 mmol)
was added at -78 °C a 1 M THF solution (0.75 mL) of
di(p-fluorophenoxy)hexylborane (0.75 mmol) and LDA (0.75
mmol) prepared by the addition of a hexane solution of BuLi (0.47
mL of a 1.6 M solution, 0.75 mmol) to diisopropylamine (76 mg,
0.75 mmol) in THF (5 mL). The mixture was stirred at -40 °C for
3 h and at room temperature for 0.5 h. Then the mixture was cooled
to 0 °C, and a THF solution (5 mL) of pinacol (591 mg, 5 mmol)
was added. After being stirred at 0 °C for 0.5 h and at room
temperature for 2 h, the mixture was poured into water and extracted
with ether three times. The combined organic layer was dried over
MgSO4 and concentrated under reduced pressure. Purification by
column chromatography (silica gel/hexane-CH2Cl2 gradient) gave
4a (143 mg) in 72% yield: IR (neat) 2926, 2855, 1662, 1467, 1146
172.92; HRMS (EI) calc. for C25H38FO4B 432.2847, found 432.2844.
(E)-2-[3-Fluoro-1-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)dec-
3-en-4-yl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4f): IR (neat)
2979, 2931, 2859, 1664, 1146 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 0.88 (t, J ) 7.1 Hz, 3H), 1.19-1.27 (m, 8 H), 1.19 (s, 12 H),
1.27 (s, 12 H), 1.79-1.84 (m, 2H), 2.02 (t, J ) 7.4 Hz, 2H), 2.39
(dt, J ) 22.6, 8.2 Hz, 2H), 5.05 (t, J ) 5.1 Hz, 1H); 19F NMR
(CDCl3, 376 MHz) δ -85.71 to -85.58 (m, 1F); 13C NMR (CDCl3,
100 MHz) δ 14.09, 22.05 (2C), 22.59, 24.15 (2C), 24.33 (d, 2JC-F
3
) 30.7 Hz), 24.70 (4C), 28.08 (d, JC-F ) 10.5 Hz), 28.98, 30.50
3
(d, JC-F ) 2.9 Hz), 31.76, 32.96, 81.79 (2C), 83.00 (2C), 99.91,
1
168.07 (d, JC-F ) 257.5 Hz); HRMS (EI) calcd for C23H42O4FB
412.3160, found 412.3161.
2-[(5E,7E)-8-Fluorooctadeca-5,7-dien-7-yl]-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (4g): IR (neat) 2926, 1650, 1376, 1465 cm-1
;
1H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 7.0 Hz, 3H), 0.89 (t, J
) 7.2 Hz, 3H), 1.26-1.53 (m, 20H), 1.32 (s, 12H), 2.08 (dt, J )
6.9, 7.0 Hz, 2H), 2.35 (dt, J ) 24.1, 7.7 Hz, 2H), 5.71 (dt, J )
15.9, 7.0 Hz, 1H), 5.98 (d, J ) 15.8 Hz, 1H); 19F NMR (376 MHz,
CDCl3) δ -88.08 to -87.94 (m, 1F); 13C NMR (100 MHz, CDCl3)
δ 13.89, 14.06, 22.18, 22.64, 24.69 (4C), 26.37, 29.10, 29.11 (d,
2JC-F ) 29.8 Hz), 29.28, 29.31, 29.45, 29.56, 31.56, 31.85, 33.17,
1
cm-1; H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 7.1 Hz, 6H),
1.26-1.52 (m, 24 H), 1.28 (s, 12 H), 2.00 (t, J ) 7.2 Hz, 2H),
2.26 (dt, J ) 23.0, 7.8 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ
-85.13 (t, J ) 23.2 Hz, 1F); 13C NMR (CDCl3, 100 MHz) δ 14.08
(2C), 22.60, 22.66, 24.71 (4C), 26.42, 28.16 (d, 2JC-F ) 10.7 Hz),
29.02, 29.26, 29.31 (2C), 29.37, 29.49, 29.58, 30.60, 31.75, 31.85,
1
82.94 (2C), 169.12 (d, JC-F ) 258.0 Hz); 11B NMR (128 MHz,
3
3
83.48 (2C), 125.07 (d, JC-F ) 12.3 Hz), 133.29 (d, JC-F ) 9.1
Hz), 167.87 (d, 1JC-F ) 255.0 Hz); HRMS (EI) calcd for C24H44O2-
FB 394.3418, found 394.3418.
CDCl3) δ 30.6 (s); HRMS (EI) calcd for C24H46FO2B 396.3575,
found 396.3574.
(Z)-2-(8-Fluorooctadec-7-en-7-yl)-4,4,5,5-tetramethyl-1,3,2-di-
(E)-2-(1-Bromo-5-fluoropentadec-4-en-4-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (4h): IR (neat) 2926, 2855, 1662, 1466, 1146
oxaborolane (4b): IR (neat) 2926, 2856, 1658, 1467, 1147 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 0.86 (t, J ) 7.0 Hz, 3H), 0.88 (t, J
) 7.1 Hz, 3H), 1.26-1.51 (m, 24H), 1.25 (s, 12H), 2.10 (t, J )
6.9 Hz, 2H), 2.51 (dt, J ) 25.2, 7.6 Hz, 2H); 19F NMR (CDCl3,
1
cm-1; H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 7.1 Hz, 3H),
1.26-1.54 (m, 16H), 1.27 (s, 12H), 1.91 (q, J ) 6.9 Hz, 2H), 2.17
(t, J ) 7.7 Hz, 2H), 2.31 (dt, J ) 23.3, 7.8 Hz, 2H), 3.40 (t, J )
6.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ -82.37 to -82.24
(m, 1F); 13C NMR (100 MHz, CDCl3) δ 14.08, 22.64, 24.71 (4C),
376 MHz) δ -80.93 (t, J ) 24.4 Hz, 1F); 13C NMR (CDCl3, 100
3
MHz) δ 13.10 (2C), 21.66, 21.68, 23.69 (4C), 24.69 (d, JC-F
)
3
10.7 Hz), 26.09, 27.80, 28.02, 28.31, 28.35, 28.57, 28.62, 29.16,
26.40, 26.58 (d, JC-F ) 10.8 Hz), 29.24, 29.28, 29.31, 29.33 (d,
2
30.20 (d, JC-F ) 28.6 Hz), 30.78, 30.92, 81.97 (2C), 168.74 (d,
2JC-F ) 30.5 Hz), 29.54, 31.85, 33.42, 33.45, 33.47, 83.10 (2C),
9620 J. Org. Chem., Vol. 72, No. 25, 2007

StereoselectiVe Synthesis of (E)- and (Z)-Fluoroalkenylboronates
1
170.52 (d, JC-F ) 263.3 Hz); HRMS (EI) calcd for C21H39O2-
Hz), 29.35, 29.45, 29.48, 29.57, 29.62, 31.73, 31.84, 31.92, 32.98,
3
2
FBBr 432.2210, found 432.2210.
115.27 (d, JC-F ) 9.1 Hz), 122.95 (d, JC-F ) 11.5 Hz), 129.02
4 1
Ethyl (Z)-4-(8-Fluorooctadec-7-en-7-yl)benzoate (6). General
Procedure for the Suzuki-Miyaura Coupling Reaction. To a
toluene solution (5 mL) of Pd(PPh3)4 (29 mg, 0.025 mmol) and 4a
(198 mg, 0.5 mmol) was added a EtOH solution (0.5 mL) of KOH
(1 mmol) and ethyl 4-iodobenzoate (166 mg, 0.6 mmol) at room
temperature. The mixture was stirred at 80 °C for 2 h, poured into
a 3 M aqueous solution of NH4Cl (40 mL), and extracted with ether
three times. The combined organic phase was dried over MgSO4
and concentrated under reduced pressure. Purification by column
chromatography (silica gel/hexane-ether gradient) gave 11 (186
(d, JC-F ) 4.8 Hz), 156.86 (d, JC-F ) 256.3 Hz); HRMS (EI)
calcd for C24H45F 352.3505, found 352.3523.
Ethyl (Z)-4-(1-benzyloxy)-4-fluoroundec-4-en-5-yl)benzoate
(8): IR (neat) 3032, 2928, 2857, 1718, 1273, 1104 cm-1; 1H NMR
(CDCl3, 400 MHz) δ 0.83 (t, J ) 7.2 Hz, 3H), 1.19-1.23 (m, 8H),
1.39 (t, J ) 7.3 Hz, 3H), 1.91 (q, J ) 7.1 Hz, 2H), 2.32 (t, J ) 7.6
Hz, 2H), 2.53 (dt, J ) 23.8, 7.6 Hz, 2H), 3.56 (t, J ) 6.1 Hz, 2H),
4.37 (q, 2H), 4.53 (s, 2H), 7.27-7.36 (m, 7H), 8.00 (d, J ) 8.6
Hz, 2H); 19F NMR (CDCl3, 376 MHz) δ -107.23 (t, J ) 23.7 Hz,
1F); 13C NMR (CDCl3, 100 MHz) δ 13.98, 14.32, 22.52, 25.89 (d,
mg) in 89% yield: IR (neat) 2926, 2855, 1720, 1465 cm-1; H
2JC-F ) 29.0 Hz), 26.72, 28.46 (d, JC-F ) 2.6 Hz), 28.86, 30.91
1
3
3
2
NMR (400 MHz, CDCl3) δ 0.85 (t, J ) 7.0 Hz, 3H,), 0.89 (t, J )
7.2 Hz, 3H), 1.24-1.62 (m, 24 H), 1.39 (t, J ) 7.3 Hz, 3H), 2.31-
2.42 (m, 4 H), 4.37 (q, J ) 7.0 Hz, 2H), 7.34 (d, J ) 7.8 Hz, 2H),
8.00 (d, J ) 8.4 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ -106.48
(t, J ) 23.8 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ 14.00, 14.10,
14.33, 22.54, 22.67, 26.74, 28.46 (d, 3JC-F ) 2.9 Hz), 28.88, 29.04,
29.28 (d, 2JC-F ) 25.3 Hz), 29.32, 29.53, 29.58, 30.94, 30.98, 31.55,
31.88, 60.79, 116.87 (d, 2JC-F ) 12.5 Hz), 128.51, 128.71 (d, 4JC-F
(d, JC-F ) 3.8 Hz), 31.52, 60.79, 69.01, 72.93, 117.58 (d, JC-F
) 11.5 Hz), 127.57, 127.61 (2C), 128.35 (2C), 128.59, 128.67 (d,
4JC-F ) 3.6 Hz, 2C), 129.23 (2C), 138.37, 142.34 (d, 3JC-F ) 2.6
1
Hz), 155.81 (d, JC-F ) 254.9 Hz), 166.50; HRMS (EI) calcd for
C27H35FO3 426.2570, found 426.2571.
(3Z,5E)-2-(3-Fluoro-4-hexyl-6-phenylhexa-3,5-dienyl)-4,4,5,5-
tetramethyl-1,3-dioxolane (9): IR (neat) 29.30, 1654, 1447, 1157
1
cm-1; H NMR (CDCl3, 400 MHz) δ 0.90 (t, J ) 6.8 Hz, 3H),
3
) 3.1 Hz, 2C), 129.23 (2C), 142.51 (d, JC-F ) 2.2 Hz), 156.64
1.21 (s, 12H), 1.22-1.49 (m, 8H), 1.82-1.88 (m, 2H), 2.24 (t, J
) 7.8 Hz, 2H), 2.49 (dt, J ) 23.4, 8.3 Hz, 2H), 5.08 (t, J ) 4.9
Hz, 1H), 6.46 (d, J ) 16.6 Hz, 1H), 7.20 (d, J ) 16.1 Hz, 1H),
7.18-7.45 (m, 5H); 19F NMR (CDCl3, 376 MHz) δ -107.36 (t, J
) 23.7 Hz, 1F); 13C NMR (CDCl3, 100 MHz) δ 14.09, 22.05 (2C),
1
(d, JC-F ) 253.9 Hz), 166.56; HRMS (EI) calcd for C27H43FO2
418.3247, found 418.3251.
(Z)-8-Fluoro-7-phenyl-7-octadecene (5a): IR (neat) 2935, 2856,
1685, 1466 cm-1; H NMR (400 MHz, CDCl3) δ 0.85 (t, J ) 7.1
1
2
3
Hz, 3H), 0.88 (t, J ) 6.8 Hz, 3H), 1.22-1.28 (m, 22H), 1.58 (q, J
) 7.6 Hz, 2H), 2.28-2.42 (m, 4H), 7.20-7.34 (m, 5H); 19F NMR
(376 MHz, CDCl3) δ -108.65 (t, J ) 23.7 Hz, 1F). 13C NMR
(100 MHz, CDCl3) δ 14.04, 14.12, 22.60, 22.69, 26.84, 28.50 (d,
3JC-F ) 2.5 Hz), 28.97, 29.17, 29.26, 29.45, 29.48(d, 2JC-F ) 27.5
22.64, 24.19 (2C), 24.42 (d, JC-F ) 28.0 Hz), 26.30 (d, JC-F )
3.8 Hz), 29.16 (d, 3JC-F ) 2.4 Hz), 29.40, 31.68, 33.19, 81.87 (2C),
3
2
99.78, 116.09 (d, JC-F ) 8.6 Hz), 122.25 (d, JC-F ) 11.5 Hz),
4
126.26 (2C), 126.76 (d, JC-F ) 4.8 Hz), 127.07, 128.53 (2C),
137.91, 158.19 (d, 1JC-F ) 260.9 Hz); HRMS (EI) calcd for C25H37-
FO2 388.2777, found 388.2778.
2
Hz), 29.58, 31.29, 31.33, 31.62, 31.91, 117.45 (d, JC-F ) 12.3
Hz), 126.49, 127.93 (2C), 128.72 (d, 4JC-F ) 3.3 Hz, 2C), 137.61
(5E,7Z)-8-Fluoro-7-phenyloctadeca-5,7-diene (10): IR (neat)
3032, 2957, 2926, 2855, 1660, 1465 cm-1; 1H NMR (CDCl3, 400
MHz) δ 0.87 (t, J ) 7.3 Hz, 3H), 0.88 (t, J ) 6.7 Hz, 3H), 1.28-
1.43 (m, 18H), 1.61 (q, J ) 7.6 Hz, 2H), 2.07 (dt, J ) 7.0, 7.2 Hz,
2H), 2.48 (dt, J ) 24.2, 7.7 Hz, 2H), 5.24 (dt, J ) 15.6, 7.2 Hz,
1H), 6.22 (dd, J ) 15.5, 1.6 Hz, 1H), 7.18-7.37 (m, 5H); 19F NMR
(CDCl3, 376 MHz) δ -103.75 (t, J ) 24.8 Hz, 1F); 13C NMR
(CDCl3, 100 MHz) δ 13.91, 14.11, 22.24, 22.69, 26.71, 28.75 (d,
2JC-F ) 28.0 Hz), 29.01, 29.34, 29.38, 29.57, 29.60, 31.51, 31.90,
3
1
(d, JC-F ) 2.9 Hz), 155.74 (d, JC-F ) 250.1 Hz); HRMS (EI)
calcd for C24H39F 346.3036, found 346.3036.
(E)-8-Fluoro-7-phenyl-7-octadecene (5b): IR (neat) 2956, 2925,
2855, 1688, 1466 cm-1; H NMR (CDCl3, 400 MHz) δ 0.85 (t, J
1
) 7.0 Hz, 3H), 0.88 (t, J ) 6.8 Hz, 3H), 1.22-1.49 (m, 24H),
2.10 (dt, J ) 23.2, 7.6 Hz, 2H), 2.38-2.39 (m, 2H), 7.13-7.33
(m, 5 H); 19F NMR (CDCl3, 376 MHz) δ -111.99 (t, J ) 23.2 Hz,
1F); 13C NMR (CDCl3, 100 MHz) δ 14.07, 14.12, 22.62, 22.68,
3
2
2
3
27.71 (d, JC-F ) 1.7 Hz), 28.90, 28.95, 29.26 (d, JC-F ) 28.3
Hz), 29.29, 29.31, 29.51, 29.57, 29.93, 29.99, 31.63, 31.90, 119.31
(d, 2JC-F ) 18.9 Hz), 126.61, 128.11 (2C), 129.04 (d, 4JC-F ) 2.9
32.92, 119.67 (d, JC-F ) 18.4 Hz), 125.92 (d, JC-F ) 5.5 Hz),
4
126.84, 127.96 (2C), 130.03 (d, JC-F ) 1.9 Hz, 2C), 133.52 (d,
3JC-F ) 10.3 Hz), 135.55 (d, 3JC-F ) 3.8 Hz), 157.46 (d, 1JC-F
)
3
1
Hz, 2C), 139.39 (d, JC-F ) 9.1 Hz), 157.08 (d, JC-F ) 249.3
Hz); HRMS (EI) calcd for C24H39F 346.3036, found 346.3052.
(5E,7Z)-8-Fluoro-7-hexyloctadeca-5,7-diene (7): IR (neat) 3040,
2926, 2855, 1665, 1466, 1166 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 0.84-0.94 (m, 9H), 1.22-1.53 (m, 28 H), 2.06-2.15 (m, 4 H),
2.27 (dt, J ) 24.2, 7.7 Hz, 2H), 5.57 (dt, J ) 16.2, 7.0 Hz, 1H),
6.41 (dd, J ) 16.1, 1.2 Hz, 1H); 19F NMR (CDCl3, 376 MHz) δ
-110.56 (t, J ) 24.4 Hz, 1F); 13C NMR (CDCl3, 100 MHz) δ
13.96, 14.06, 14.10, 22.29, 22.67, 22.70, 26.61 (d, 3JC-F ) 4.8 Hz),
255.8 Hz); HRMS (EI) calcd for C24H37F 344.2879, found
344.2878.
Acknowledgment. We thank Prof. Norio Miyaura for his
helpful advice.
Supporting Information Available: 1H and 13C NMR spectra
of all boronate and fluoroalkene products. This material is available
free of charge via the Internet at http://pubs.acs.org.
2
3
26.82, 29.06 (d, JC-F ) 28.7 Hz), 29.26, 29.27 (d, JC-F ) 2.4
JO701784T
J. Org. Chem, Vol. 72, No. 25, 2007 9621