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M.-L. Yao et al. / Tetrahedron Letters 51 (2010) 853–855
Cl
B
LiO
Ar
O
Ar
Ar1
H
Ar
Ar1
HBCl2
Cl
B
H
OH
Ph
H
O
Ar1
H2BCl
Ph
Ph
0ºC to rt
Intermediate 1
Z
Z
Z
Scheme 3. Deoxygenation of alkoxides using dichloroborane.
Intermediate 1
Z = Br, 65%;
Z = CN, 50%
Scheme 6. Doxygenation of alcohols using monochloroborane.
Table 1
a
Deoxygenation through alkoxide using HBCl2
The new deoxygenation also works well for benzylic alcohols
bearing a cyclopropyl group (Scheme 4). The tolerance of the cyclo-
propyl group indicates that the reaction most probably proceeds
through a concerted reaction mechanism rather than through a
carbocation intermediate. In addition, vinyl groups are stable un-
der the reaction conditions.
As noted in entries 9 and 13 (Table 1), the deoxygenation reac-
tion can lead to undesired chlorinated by-products. Therefore, we
examined the possibility of using H2BCl in the place of HBCl2 which
would result in the formation of an alkoxide intermediate bearing
only hydrogen atoms on the boron attached to the oxygen. This
modification successfully inhibited the formation of the chlori-
nated by-product, entry 9. Little improvement was noted in reac-
tions using 9-hydroxyfluorene. However, the deoxygenation of
primary alcohols using H2BCl is remarkable though the reactions
produce only moderate yields (Scheme 5).
H
R
HO
R
1. n-BuLi, DCM, 0ºC
Z
2. HBCl2
Y
Z
Y
Entry
R
Y
Z
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
H
H
H
H
H
H
H
H
H
H
Ph
Me
H
H
H
63
67
70
82
p-Cl
p-F
p-Me
o-OMe
p-OMe
H
H
H
H
H
H
p-F
H
H
84
p-OMe
3,4,5-(OMe)3
p-NO2
p-OBn
p-OMOM
H
72 (95)c
79
58
65d (78)c
76e
96
H
—
H
94
f
56g
We also examined the possibility of generating intermediate 1
by mixing benzylic alcohols with monochloroborane (Scheme 6).
This would obviate the use of butyllithium and could be beneficial
when certain functional groups (–Br and –CN) are present. The di-
rect reaction produces the desired products in moderate yields.
In conclusion, new boron-based deoxygenation methods for
converting benzylic alcohols to diarylmethanes are reported. The
deoxygenation of alkoxides using dichloroborane not only expands
our knowledge in organoboron dihalide chemistry but also pro-
vides evidence helpful in understanding the importance of Lewis
acidity in previously reported deoxygenation methods.
a
b
c
d
e
f
All reactions were carried out on a 1.5 mmol scale.
Isolated yield.
H2BCl was used in place of HBCl2.
A 12% yield of diarylchloromethane was isolated.
The MOM group was cleaved during reduction.
9-hydroxyfluorene was used as starting material.
A 21% yield of 9-chloro-9H-fluorene was isolated.
g
R
1. n-BuLi, DCM, 0ºC
Acknowledgment
R
2. HBCl2
R = H, 77% ;
OH
Ph
R = Ph, 74%
We wish to thank the Department of Energy and the Robert H.
Cole Foundation for financial support of this research.
1. n-BuLi, DCM, 0ºC
2. HBCl2
Ph
Ph
Ph
OH
83%
References and notes
Scheme 4. Deoxygenation of alkoxides using dichloroborane.
1. Eisch, J. J.; Liu, Z.-R.; Boleslawski, M. P. J. Org. Chem. 1992, 57, 2143.
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Kabalka, G. W.; Yao, M.-L.; Borella, S.; Wu, Z. Chem. Commun. 2005, 2492.
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2008, 73, 2668; (b) Yao, M-L.; Quinn, M. P.; Kabalka, G. W. Heterocycles 2009.
ASAP.
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T.; Rahman, S. M. Synth. Commun. 2003, 33, 3997; (b) Olah, G. A.; Kobayashi, S.;
Tashiro, M. J. Am. Chem. Soc. 1972, 94, 7488; Through bimetallic catalysis: (c)
Podder, S.; Choudhury, J.; Roy, U. K.; Roy, S. J. Org. Chem. 2007, 72, 3100; (d)
Choudhury, J.; Podder, S.; Roy, S. J. Am. Chem. Soc. 2005, 127, 6162.
chlorinated by-products may form. In previously reported methods
for deoxygenating secondary alcohols (including lithium–ammo-
nia,11 sodium borohydride–trifluoroacetic,12 zinc iodide–sodium
cyanoborohydride,13 indium trichloride–chlorodiphenylsilane,2
hypophosphorus–iodine,14 and Mo(CO)6-Lawesson’s reagent15),
ether cleavage and hydrogenolysis of halogen atoms are common
side reactions due to either high acidity or the use of strongly
reducing conditions.
7. Suzuki coupling: (a) Chodhury, S.; Georghiou, P. Tetrahedron Lett. 1999, 40,
7599; (b) Chahen, L.; Doucet, H.; Santelli, M. Synlett 2003, 1668; (c) Kuwano, R.;
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A. R.; Sehnal, P.; Taylor, R. J. K. Org. Lett. 2007, 9, 5397; Stille coupling: (i) Asselt,
R.; Elsevier, C. Tetrahedron 1994, 50, 323; Cu(I)-mediated coupling with
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Ph
Ph
Ph
Ph
OH
OH
1. n-BuLi, DCM, 0ºC
2. H2BCl
Me
42%
1. n-BuLi, DCM, 0ºC
2. H2BCl
Br
Me
Br
48%
Scheme 5. Deoxygenation of primary alkoxides using monochloroborane.