Substitution of benzylic hydroxyl groups with vinyl moieties using vinylboron dihalides

Article abstract of DOI:10.1021/ol050778v

(Chemical Equation Presented) Substitution of benzylic hydroxyl groups with vinyl moieties using vinylboron dihalides has been achieved. The reaction provides a novel method for preparing stereodefined alkenyl halides.

Full text of DOI:10.1021/ol050778v

ORGANIC
LETTERS
2
005
Vol. 7, No. 14
865-2867
Substitution of Benzylic Hydroxyl
Groups with Vinyl Moieties Using
Vinylboron Dihalides
2
George W. Kabalka,* Min-Liang Yao, Scott Borella, and Zhong-Zhi Wu
Departments of Chemistry and Radiology, The UniVersity of Tennessee,
KnoxVille, Tennessee 37996-1600
kabalka@utk.edu
Received April 11, 2005
ABSTRACT
Substitution of benzylic hydroxyl groups with vinyl moieties using vinylboron dihalides has been achieved. The reaction provides a novel
method for preparing stereodefined alkenyl halides.
Benzylic alcohols are generally transformed into the corre-
sponding halides or esters prior to reactions with nucleophiles
due to the fact that the hydroxide group is such a poor leaving
group. The direct utilization of benzylic alcohols as elec-
trophiles would be quite useful since it would be both atom
hydroxide moiety with an allyl group using allyltrimethyl-
silane represents the most attractive transformation (Scheme
1). However, to the best of our knowledge, the direct
5
1
efficient and more environmentally sound. To date, very
Scheme 1. Direct Substitution of Benzylic Hydroxyl Group
few direct substitutions have been achieved.2 Among those
-5
reported, the straightforward substitution of the benzylic
*
To whom correspondence should be addressed. Phone: (865)974-3260.
Fax: (865)974-2997.
(
1) Trost, B. M. Science 1991, 254, 1471.
(2) Dehydroxylation: (a) Singh, S.; Chhina, S.; Sharma, V. K.; Sachdev,
substitution of a benzylic hydroxyl group by a vinyl moiety
has not been achieved using a Lewis acid or transition metal
catalyst.
S. S. J. Chem. Soc., Chem. Commun. 1982, 453. (b) Ono, A.; Suzuki, N.;
Kamimura, J. Synthesis 1987, 736. (c) Olah, G. A.; Wu, A. H.; Farooq, O.
J. Org. Chem. 1991, 56, 2759. (d) Stoner, E. J.; Cothron, D. A.; Balmer,
M. K.; Roden, B. A. Tetrahedron 1995, 51, 11043. (e) Miyai, T.; Ueba,
M.; Baba, A. Synlett 1999, 182. (f) Gevorgyan, V.; Rubin, M.; Benson, S.;
Liu, J.-X.; Yamamoto, Y. J. Org. Chem. 2000, 65, 6179. (g) Gordon, P.
E.; Fry, A. J. Tetrahedron Lett. 2001, 42, 831. (h) Yasuda, M.; Onishi, Y.;
Ueba, M.; Miyai, T.; Baba, A. J. Org. Chem. 2001, 66, 7741.
We have investigated the chemistry of boron halide
derivatives for many years, and several novel reactions have
6,7
7b-e
7a,8
been developed. The alkylation
and dialkenylation
of aryl aldehydes using alkylboron dihalides and dialkenyl-
boron halides were reported previously. Encouraged by these
initial results, we turned our attention to the chemistry of
(3) Reaction with KCN: (a) Fleming, I.; Loreto, M. A.; Wallace, I. H.
M. J. Chem. Soc., Perkin Trans. 1 1986, 349. (b) Wilk, B. K. Synth.
Commun. 1993, 23, 2481. (c) Aesa, M. C.; Ba a´ n, G.; Nov a´ k, L.; Sz a´ ntay,
C. Synth. Commun. 1995, 25, 1545.
(
4) Reaction with organic reactants: with carbon-carbon multi-bond:
(
1
2
a) Cravotto, G.; Giovenzana, G. B.; Sisti, M.; Palmisano, G. Tetrahedron
996, 52, 13007. (b) Bisaro, F.; Prestat, G.; Vitale, M.; Poli, G. Synlett
002, 1823. (c) Marquet, J.; Moreno-Manas, M. Chem. Lett. 1981, 173.
with malonate derivatives: (d) Bott, K. Angew. Chem. 1965, 77, 967. (e)
Kell, D. R.; McQuillin, F. J. J. Chem. Soc., Perkin Trans. 1 1972, 2100. (f)
Takacs, J. M.; Xu, Z.; Jiang, X.-T.; Leonov, A. P.; Theriot, G. C. Org.
Lett. 2002, 4, 3843.
(5) (a) Cella, J. A. J. Org. Chem. 1982, 47, 2125. (b) Kaur, G.; Kaushik,
M.; Trehan, S. Tetrahedron Lett. 1997, 38, 2521. (c) Rubin, M.; Gevorgyan,
V. Org. Lett. 2001, 3, 2705. (d) Yasuda, M.; Saito, T.; Ueba, M.; Baba, A.
Angew. Chem., Int. Ed. 2004, 43, 1414.
(6) For BX3-mediated reactions: (a) Kabalka, G. W.; Wu, Z. Tetrahedron
Lett. 2000, 41, 579. (b) Kabalka, G. W.; Wu, Z.; Ju, Y. Tetrahedron Lett.
2001, 42, 5793. (c) Kabalka, G. W.; Wu, Z.; Ju, Y. Synthesis 2004, 2927.
1
0.1021/ol050778v CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/11/2005

9
11
alkenylboron dihalides. (Z)-2-Halo-1-alkenylboron dihalide
presence of 1 equiv of n-BuLi in dry dichloromethane.
1
13
derivatives can be readily prepared by the haloboration of
terminal alkynes using 1 equiv of boron trihalide. The
reaction occurs in a stereo- and regioselective fashion via
the syn addition of the B-X moiety to the carbon-carbon
triple bond.10
Analysis of the H and C NMR spectroscopic data for 3a
revealed that the Z isomer formed exclusively. Thus, the
configuration of the vinyl group is retained in the reaction.
The Z stereochemistry is unambiguously supported by X-ray
12
analysis of 3b (Figure 1).
We wish to report the substitution of benzylic hydroxyl
groups by alkenylboron dihalides. In this new reaction,
alkenylboron dihalides act as both Lewis acids and reactants.
This transformation, in the absence of transition metals, is
particularly appealing from an industrial perspective. Phar-
maceutical syntheses often involve the challenging step of
removing transition metals from intermediates.
To examine the scope of the reaction, different types of
benzylic alcohols were prepared and subjected to the reaction
conditions (Table 1). Both alkenylboron dichlorides and
Table 1. Coupling of Benzylic Alcohols with Vinylboron
Dihalides
Figure 1. ORTEP plot of compound 3b.
The reaction of diphenylmethanol (1a) and (Z)-2-chloro-
2-phenylethenylboron dichloride was chosen as the model
system. After surveying potential solvents and bases, we
found that the new reaction proceeds most effectively in the
a
Reaction carried out at room temperature on a 1.5 mmol scale in DCM
b
using n-BuLi as the base (for the detailed procedure, see ref 11). Yield of
isolated product based on the precursor of halovinylboron dihalide (alkyne).
-Bromobenzyl bromide was isolated.
(7) For RBX2- and R2BX-mediated reactions: (a) Kabalka, G. W.; Wu,
Z.; Ju, Y. Org. Lett. 2002, 4, 1491. (b) Kabalka, G. W.; Wu, Z.; Trotman,
S. E.; Gao, X. Org. Lett. 2000, 2, 255. (c) Kabalka, G. W.; Wu, Z.; Ju, Y.
Tetrahedron 2001, 57, 1663. (d) Kabalka, G. W.; Wu, Z.; Ju, Y. Tetrahedron
Lett. 2000, 41, 5161. (e) Kabalka, G. W.; Wu, Z.; Ju, Y. Tetrahedron Lett.
c
4
2
001, 42, 6239.
8) Dialkenylation of aldehydes using other Lewis acids, see: (a)
alkenylboron dibromides derived from aryl alkynes produced
the desired products in moderate to good yields. Alkenyl-
boron dihalides derived from aliphatic alkynes were unre-
active. Due to the ready decomposition of alkenyl bromides
on silica gel, the isolated yields are somewhat lower for the
alkenylboron dibromides. The NMR spectra of all products
reveal that only the Z isomers formed. Under the reaction
conditions, most functional groups are tolerated. It is quite
(
Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2002, 4, 1491. (b) Miranda, P.
O.; D ´ı az, D. D.; Padr o´ n, J. I.; Ram ´ı rez, M. A.; Mart ´ı n, V. S. J. Org. Chem.
2
005, 70, 57. (c) Yadav, J. S.; Reddy, B. V. S.; Eeshwaraiah, B.; Gupta,
M. K.; Biswas, S. K. Tetrahedron Lett. 2005, 46, 1161.
(
9) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2004, 6, 3929.
10) (a) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents; Academic
(
Press: New York, 1988. (b) Lappert, M. F.; Prokai, B. J. Organomet. Chem.
964, 1, 384. (c) Suzuki, A. Pure Appl. Chem. 1986, 58, 829. (d) Suzuki,
A. ReV. Heteroatom Chem. 1997, 17, 271.
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Org. Lett., Vol. 7, No. 14, 2005

remarkable that the methoxy group is tolerated, since it is
concerted rearrangement and supports formation of a benzylic
cation intermediate. Further evidence supporting a cationic
mechanism was provided by the observation that the reaction
of cyclopropyl derivative 1m produced the ring-opened
product, 5 (Scheme 3). A cationic mechanism could also
well-known that Lewis acids such as BBr
in cleaving ether linkages.13
3
are quite effective
Though a detailed mechanistic study has not been under-
taken, the reaction of lithium benzyloxide with alkenylboron
dihalide presumably generates (halovinyl)benzyloxyboron
halide intermediate 4, which undergoes a rearrangement to
3
(Scheme 2).
Scheme 3. Reaction of a Cyclopropyl Derivative
Scheme 2 Proposed Intermediate 4 for Alkenyl Migration
explain the failure of 1k to generate 3k since loss of a
â-hydrogen in the benzylic cation generated from 1k would
be expected to be quite rapid.
A new, straightforward substitution of benzylic hydroxide
moieties with stereodefined vinyl groups has been developed.
The reaction provides a novel route to trisubstituted alkenyl
halides from readily available benzylic alcohols and terminal
alkynes (the precursor of (Z)-alkenylboron dihalides).
To gain mechanistic insight, a reaction was carried out
using (S)-1g. Racemization occurred, which precludes a
1
4
(
11) Typical Experimental Procedure. Boron trihalide (1.5 mmol),
alkyne (1.5 mmol), and dry dichloromethane (8 mL) were combined in a
0 mL flask and stirred for 1 h at room temperature. In a separate flask,
Acknowledgment. We wish to thank the donors of the
Petroleum Research Foundation, administered by the Ameri-
can Chemical Society, and the Robert H. Cole Foundation
for support of this research. The authors also thank Brandy
Belue and Cara Nygren for X-ray analysis.
5
the benzylic alcohol (1.6 mmol) in dry dichloromethane (8 mL) was treated
with n-butyllithium (1.0 mL of a 1.6 M solution in hexanes) at 0 °C and
warmed to room temperature. After stirring at room temperature for 30
min, the solution was transferred to the first flask and the mixture was
allowed to stir overnight. Water (20 mL) was added to quench the reaction.
The reaction mixture was extracted with ethyl acetate and dried over
anhydrous MgSO4. The solvent was removed in vacuo and the product
purified by silica gel column chromatography using hexane as an eluent to
Supporting Information Available: Typical experimen-
tal procedure and analytical data for all products, including
CIF data for 3b. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
provide 3a. H NMR (250.13 MHz, CDCl3 with TMS as the internal
standard): δ 7.56-7.59 (m, 2H), 7.17-7.30 (m, 13H), 6.59 (d, J ) 9.47
Hz, 1H), 5.42 (d, J ) 9.47 Hz, 1H). C NMR (62.89 MHz, CDCl3): δ
1
3
1
42.9, 137.8, 133.4, 129.5, 128.6, 128.3, 126.6, 50.8. Anal. Calcd for C21H17-
Cl: C, 82.75; H, 5.62. Found: C, 82.57; H, 5.65.
12) For details of the crystallographic data of compound 3b, see
Supporting Information.
13) Meyers, A. I.; Nolen, R. L.; Collington, E. W.; Narwid, T. A.;
Strickland, R. C. J. Org. Chem. 1973, 38, 1974.
OL050778V
(
(14) Determined by chiral GC-MS. Column: Varian CP-chirasil-DEX
CB 25 m × 0.25 mm × 0.25 mm; initial temperature/initial time ) 50
°C/3 min; final temperature/final time ) 200 °C/10 min; rate ) 2 °C/min.
(
Org. Lett., Vol. 7, No. 14, 2005
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