Efficient synthesis of aryl vinyl ethers exploiting 2,4,6- trivinylcyclotriboroxane as a vinylboronic acid equivalent

Article abstract of DOI:10.1021/jo049314l

The synthesis of functionalized aryl vinyl ether derivatives can be readily achieved utilizing a room-temperature copper(II) acetate mediated coupling of substituted phenols with 2,4,6-trivinylcyclotriboroxane-pyridine complex in the presence of a suitable base. The scope of the procedure was demonstrated by the generation of an array of substituted aryl vinyl ethers. The reaction was seen to be tolerant of a diverse range of functional groups yielding products in high isolated yields. We have shown that one role of an amine base in the reaction sequence is the in situ generation of an amine coordinated boroxine ring. An X-ray crystal structure and low temperature ¹¹B NMR study of 2,4,6-trivinylcyclotriboroxane-pyridine complex demonstrated the nature of the tetracoordinate boron species, which may have a key role to play within the reaction sequence.

Full text of DOI:10.1021/jo049314l

Efficien t Syn th esis of Ar yl Vin yl Eth er s Exp loitin g
2,4,6-Tr ivin ylcyclotr ibor oxa n e a s a Vin ylbor on ic Acid Equ iva len t
Neola F. McKinley and Donal F. O’Shea*
Centre for Synthesis and Chemical Biology, Conway Institute, Department of Chemistry,
University College Dublin, Belfield, Dublin 4, Ireland
donal.f.oshea@ucd.ie
Received April 23, 2004
The synthesis of functionalized aryl vinyl ether derivatives can be readily achieved utilizing a room-
temperature copper(II) acetate mediated coupling of substituted phenols with 2,4,6-trivinylcyclo-
triboroxane-pyridine complex in the presence of a suitable base. The scope of the procedure was
demonstrated by the generation of an array of substituted aryl vinyl ethers. The reaction was seen
to be tolerant of a diverse range of functional groups yielding products in high isolated yields. We
have shown that one role of an amine base in the reaction sequence is the in situ generation of an
amine coordinated boroxine ring. An X-ray crystal structure and low temperature 11B NMR study
of 2,4,6-trivinylcyclotriboroxane-pyridine complex demonstrated the nature of the tetracoordinate
boron species, which may have a key role to play within the reaction sequence.
In tr od u ction
Recently we described the pyridine complex of 2,4,6-
trivinylcyclotriboroxane 1 as a bench-stable synthetic
equivalent of unstable vinylboronic acid (Figure 1).
Cyclodehydration of vinyl boronic acid into its corre-
sponding trivinyl boroxine did not impede its reactivity
in palladium-catalyzed Suzuki-Miyaura cross-coupling
reactions with substituted aryl halides facilitating the
generation of substituted styrenes in high yields.1
We now report a further important synthetic utilization
of this reagent in a carbon-oxygen bond-forming reaction
for the generation of aryl vinyl ethers. Aryl vinyl ethers
have wide synthetic applications and are employed as key
synthetic intermediates for the generation of new poly-
meric materials,2 as dienophiles for cycloaddition reac-
tions,3 in cyclopropanations,4 in hydroformylations,5 and
in natural product analogue synthesis.6 Traditional
methods for their generation require an elimination
under basic conditions from R-bromo ethers to generate
the double bond.7 The base-catalyzed reaction of phenols
with acetylene under high temperature and pressure
F IGURE 1. 2,4,6-Trivinylcyclotriboroxane-pyridine complex.
conditions was the first method developed which used
an unsaturated carbon-carbon bond as the vinyl source.8
As a result of these harsh conditions there has been a
recent resurgence in the development of improved meth-
ods. The new methods are based upon the coupling of
various vinyl sources with phenols in conjunction with a
metal catalyst. The use of vinyl acetate in an iridium-
catalyzed reaction with phenols in toluene at 100 °C has
been shown to be a viable route to this class of com-
pound.9 Tetravinyltin has also been shown to effectively
react with phenols in a room-temperature copper(II)
acetate mediated reaction in acetonitrile under an at-
mosphere of oxygen.10 But the requirement of stoichio-
metric amounts of the tetravinyltin reagent and the
known high toxicity of the tin byproducts could be
considered disadvantageous for this methodology. Our
aim was to develop 1 as a viable reagent for the
generation of aryl vinyl ethers exploiting mild copper-
mediated coupling conditions. The reaction conditions
used for this coupling are based on those developed by
Evans, Chan, and Lam for the coupling of arylboronic
acids with phenols or amines.11 Recently, copper-medi-
ated coupling of trans-1-hexenylboronic acid with 3,5-di-
tert-butylphenol has been reported in a 52% yield.12
(1) (a) Kerins, F.; O’Shea, D. F. J . Org. Chem. 2002, 67, 4968. (b)
Matteson, D. S. J . Org. Chem. 1962, 27, 3712. (c) Coleman, C. M.;
O’Shea, D. F. J . Am. Chem. Soc. 2003, 125, 4054.
(2) Kojima, K.; Sawamoto, M.; Higashimura, T. Macromolecules
1989, 22, 1552.
(3) (a) Savinov, S. N.; Austin, D. J . Chem. Commun. 1999, 1813. (b)
Marko, I. E.; Evans, G. R.; Declercq, J .-P. Tetrahedron 1994, 50, 4557.
(c) El-Nabi, H. A. A. Tetrahedron 1997, 53, 1813.
(4) (a) Maligres, P. E.; Waters, M. M.; Lee, J .; Reamer, R. A.; Askin,
D.; Ashwood, M. S.; Cameron, M. J . Org. Chem. 2002, 67, 1093. (b)
Wenkert, E.; Alonso, M. E.; Buckwalter, B. L.; Sanchez, E. L. J . Am.
Chem. Soc. 1983, 105, 2021.
(5) Lyle, F. R. U.S. Patent 5 973 257, 1985; Chem. Abstr. 1985, 65,
2870.
(6) Ahrendt, K. A.; Bergman, R. G.; Ellman, J . A. Org. Lett. 2003,
5, 1301.
(7) Maligres, P. E.; Waters, M. M.; Lee, J .; Reamer, R. A.; Askin, D.
J . Org. Chem. 2002, 67, 1093.
(8) Reppe, W. Ann. 1956, 601, 84.
(9) Okimoto, Y.; Sakaguchi, S.; Ishii, Y. J . Am. Chem. Soc. 2002,
124, 1590.
(10) Blouin, M.; Frenette R. J . Org. Chem. 2001, 66, 9043.
10.1021/jo049314l CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/24/2004
J . Org. Chem. 2004, 69, 5087-5092
5087

McKinley and O’Shea
SCHEME 2. Gen er a tion of Am in e-Com p lexed
SCHEME 1. Syn th esis of Ar yl Vin yl Eth er s
Tr isu bstitu ted Bor oxin e Rin gs
TABLE 1. In vestiga tion of Cou p lin g Rea ction
Con d ition s
equiv equiv equiv of conversiona,b
entry phenol solvent of Cu
of 1 pyridine
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
4-Ph
4-Ph
4-Ph
4-Ph
4-Ph
4-Ph
4-Ph
4-Ph
4-Ph
4-Cl
4-Cl
4-Cl
4-Ph
4-Ph
4-Ph
4-Ph
4-Cl
4-Ph
4-Ph
4-Ph
4-Cl
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2 0.75
CH2Cl2 0.50
CH2Cl2 0.25
CH2Cl2 0.10
CH3CN 0.75
1
1
1
1
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
0
99
95
70
95
94
44
18
85
27
0.66
0.33
0.66
0.66
0.66
0.66
0.66
0.66
1
0.66
0.66
0.66
0.66
0.66
1
0.33, the reactions failed to achieve a satisfactory conver-
sion (70%) for 4-phenylphenol (entry 3). As a result, we
chose a 0.66 molar ratio of reagent 1 for our optimal
reaction conditions. Examination of required levels of
copper for the reaction showed that reduction of the Cu-
(OAc)2 molar ratio to 0.75 with 0.66 molar ratio of 1
maintained high product conversion for 4-phenylphenol
(95%) but not 4-chlorophenol (68%) (entries 4 and 12).
Further reduction in copper levels below the 0.75 molar
ratio gave rise to inefficient coupling (entries 5 and 6),
which led us to conclude that a stoichiometric quantity
of copper would be required to develop a general set of
reaction conditions.
A survey of other reaction solvents, acetonitrile and
THF, showed that acetonitrile is an effective solvent for
the reaction but THF was not (entries 8 and 9) from
which we decided that dichloromethane would be our
solvent of choice for the reaction. An examination of the
benefit of an oxidant within the reaction sequence showed
that the reaction was improved if carried out under an
atmosphere of oxygen.11a,d,12 When using 0.25 molar equiv
of Cu(OAc)2 the conversion was improved from 44% to
83% but the reaction did not reach completion (compare
entries 6 and 14). In contrast, when the reaction was
carried out under an atmosphere of nitrogen using a
stoichiometric equivalent of Cu(OAc)2 the reaction con-
version was significantly reduced to 33% (entry 15).
It has been previously reported that the addition of
molecular sieves to the reaction was beneficial in the
coupling of arylboronic acids with phenols.11a,13 Improved
yields were attributed to the prevention of the copper-
mediated reaction of boronic acid with water which gave
rise to phenols which further reacted with remaining
boronic acid to generate their subsequent coupled byprod-
ucts. One possible source of this water would be from the
in situ generation of trisubstituted boroxines 4 from
cyclodehydration of three molecules of boronic acid
(Scheme 2).
THF
CH2Cl2
CH2Cl2
0.75
1
1
99
91
68
CH2Cl2 0.75
CH2Cl2 0.50
CH2Cl2 0.25
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
90c
83c
33d
52
1
1
1
1
1
1
1
1
0
0
0
0
51
0.66
0.66
0.66
0.66
50e
86f
100g
100g
0
a
Room temperature, 24 h (reaction times are not minimized).
Average of two runs. c Reaction conducted under oxygen. Reac-
b
d
tion conducted under nitrogen. e 1 molar equiv of Na2CO3 added.
f 1 molar equiv of K2CO3 added. 1 molar equiv of Cs2CO3 added.
g
Resu lts a n d Discu ssion
Op tim iza tion of Cou p lin g Con d ition s. For our
preliminary investigation to determine the optimal reac-
tion conditions we chose 4-phenyl- and 4-chlorophenol as
our test substrates, which we anticipated would give us
an indication of the phenol reactivity range for the
reaction. To test the suitability of 1 for this transforma-
tion, a study of varying reaction conditions was under-
taken. The first conditions attempted were an equal
stoichiometric ratio of phenol, Cu(OAc)2 and 1 (formally
3 molar equiv of H2CdCH-B-O), with 10 molar equiv
of pyridine in dry dichloromethane, at room temperature,
for 24 h (Scheme 1).
Encouragingly, the reagent 1 effectively participated
in the reaction to give complete conversion to the desired
product as determined by GC, GC-MS, and 1H NMR
(Table 1, entries 1 and 10). We next examined the effect
of lowering the molar equivalents of 1 to 0.66, effectively
2 molar equiv of H2CdCH-B-O. For both phenol sub-
strates the reaction conversion remained above 90%
(entries 2 and 11). Upon lowering the molar ratio of 1 to
As we start with a preformed boroxine ring already
complexed with 1 mol of pyridine, we anticipated that
the inclusion of molecular sieves in the reaction would
be unnecessary and that it would facilitate an investiga-
tion of the role of the base in the reaction sequence.
Although 1 already has one molecule of pyridine associ-
ated with it, omitting additional pyridine from the
(11) (a) Evans, D. A.; Katz, J . L.; West, T. R.; Tetrahedron Lett. 1998,
39, 2937. (b) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M.
P. Tetrahedron Lett. 1998, 39, 2933. (c) Lam P. Y. S.; Clark, C. G.;
Saubern, S.; Adams, J .; Winters, M. P.; Chan, D. M. T.; Combs, A.
Tetrahedron Lett. 1998, 39, 2941. (d) Lam, P. Y. S.; Vincent, G.; Clark,
C. G.; Deudon, S.; J adhav, P. K. Tetrahedron Lett. 2001, 42, 3415. (e)
Quach, T. D.; Batey, R. A. Org. Lett. 2003, 5, 1381. (f) Ley, S. V.;
Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400 (review).
(12) Lam, P. Y. S.; Vincent, G.; Bonne, D.; Clark, C. G. Tetrahedron
Lett. 2003, 44, 4927.
(13) Sagar, A. D.; Tale, R. H.; Adude, R. N. Tetrahedron Lett. 2003,
44, 7061.
5088 J . Org. Chem., Vol. 69, No. 15, 2004

2,4,6-Trivinylcyclotriboroxane-Pyridine Complex
TABLE 2. P a r a llel Gen er a ted Ar r a y of Ar yl Vin yl
Eth er s
entry phenol
R
product conversiona (%) yielda (%)
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
p-Ph
p-Cl
o-Br
m-I
p-CO2CH3
m-CN
p-CHO
p-OCH3
o-OCH3
3a
3b
3c
3d
3e
3f
3g
3h
3i
93
96
90
91
78
90
86
99
99
99
98
94
85
76
83
76
68
92
84
90
70
67
88
80
F IGURE 2. Phenylboronic acid 6, triphenylboroxine 7, and
triphenylboroxine pyridine complex 8.
To demonstrate individual reactions on a larger scale
we chose four phenols, 4-phenyl- 2a , 2-bromo- 2c, 3-iodo-
2d , and 4-tert-butylphenol 2j, from the library and re-
made their corresponding vinyl ethers. The reactions
were carried out on a 0.5 g scale of substituted phenol
under conditions identical to those used in the parallel
synthesis. The isolated purified product yields from each
reaction were excellent with the vinyl ethers 3a , 3c, and
3d above 90% and 3j at 80%. 3a was also re-synthesized
on the same scale using an equivalent of cesium carbon-
ate as base, which resulted in a comparable yield (93%)
as that obtained from the pyridine base reaction condi-
tions.
Role of th e Ba se in th e Rea ction Sequ en ce. It has
been shown that the coupling of arylboronic acids with
phenols fails in the absence of an amine base. Two
proposed roles of the base are as a ligand for coordination
to organocopper intermediates and/or to function as a
proton acceptor, though the exact role(s) of base within
the reaction sequence remain unclear.11a We sought to
investigate an additional possible role of the base in
regard to the boronic acid species within the reaction.
The synthesis of monoamine adducts of substituted
boroxine rings 5 has been previously described for a wide
range of amines and substituted boronic acids (Scheme
2).14,15 Typical reaction conditions for the formation of 5
would be stirring at room temperature in an organic
solvent with an equimolar quantity of amine base.15a-d
These mild reaction conditions indicate that amine
adducts of boroxine rings could be readily formed in situ
from boronic acids under the typical copper mediated
coupling conditions utilized for this class of reaction.16
To demonstrate this role of the base, we carried out a
study of the reaction of phenylboronic acid 6, triphenyl-
boroxine 7, and the pyridine complex of triphenylboroxine
8 with the phenol 2a (Figure 2).
9
10
11
12
2j
2k
2l
p-t-Bu
m-N(CH3)2
o-NHCOCH3
3j
3k
3l
a
Average of two runs.
reaction reduced by half the product conversions for both
4-phenyl and 4-chlorophenol (entries 16 and 17). A study
of inorganic bases revealed a synthetic alternative to
organic bases such as pyridine. The use of 1 molar equiv
of sodium, potassium, or cesium carbonate gave improved
conversions in comparison to the conditions that con-
tained no additional pyridine base, but only cesium
carbonate resulted in a complete reaction conversion
(entries 18-21). Thus cesium carbonate could be utilized
as an alternative to an amine base if the amine coordi-
nated boroxine ring is preformed.
Syn th esis of Ar yl Vin yl Eth er s. We have tested the
scope of the reaction with a range of electronically and
functionally diverse phenols 2a -l in order to examine
the substituent tolerance of the reaction procedure (Table
2).
The optimized set of conditions employed for the
reactions were as follows: 1.0 molar equiv of phenol and
Cu(OAc)2, 0.66 molar equiv of 1 (2 molar equiv of H2Cd
CH-B-O), and 10 molar equiv of pyridine, in dichlo-
romethane, at room temperature, for 24 h. For ease of
synthetic applicability we considered it advantageous if
the reactions were not carried out under an oxygen
atmosphere, though they were exposed to ambient air
through a calcium chloride drying tube. The reactions
were carried out in parallel using a manual parallel
synthesizer. Upon reaction completion individual reac-
tions were worked up by washing with aqueous am-
monium acetate followed by analysis with GC, GC-MS,
1
Compounds 7 and 8 were synthesized by literature
methods14a,15a and chosen as the model reagents due to
the synthetic inaccessibility of vinylboronic acid.1a The
and H NMR. The reaction was successful for each phenol
derivative examined with nine derivatives giving product
conversions higher that 90% (Table 2). We discovered
that as with the coupling of arylboronic acid to phenols,
this reaction was tolerant of a wide range of sensitive
functional groups such as halo, formyl, nitrile, ester,
amino and amide. The reaction tolerated both electron-
donating and -withdrawing substituents giving good
conversions, though substrates with electron-withdraw-
ing groups were marginally lower (Table 2, entries 5 and
6). The steric hindrance of the ortho-substituted phenol
derivatives 2c, 2i, and 2l did not appear to significantly
impede the reaction with o-bromo, methoxy, and ami-
dophenol giving high conversions and yields (entries 3,
9, and 12). The reaction was also tolerant of halo-
substituted phenols with neither the bromo of 2c or the
iodo of 2d participating in a cross-coupling reaction
(entries 3 and 4).
(14) (a) Burg, A. B. J . Am. Chem. Soc. 1940, 62, 2228. (b) Snyder,
H. R.; Konecky, M. S.; Lennarz, W. J . J . Am. Chem. Soc. 1958, 80,
3611.
(15) (a) Beckmann, J .; Dakternieks, D.; Duthie, A.; Lim, A. E. K.;
Tiekink, E. R. T. J . Organomet. Chem. 2001, 633, 149. (b) Yalpani,
M.; Boese, R. Chem. Ber. 1983, 116, 3347. (c) Beckett, M. A.;
Brassington, D. S.; Owen, P.; Hursthouse, M. B.; Light, M. E.; Malik,
K. M. A.; Varma, K. S. J . Organomet. Chem. 1999, 585, 7. (d) Beckett,
M. A.; Strickland, G. C.; Varma, K. S.; Hibbs, D. E.; Hursthouse, M.
B.; Malik, K. M. A. J . Organomet. Chem. 1997, 535, 33. (e) Beckett,
M. A.; Strickland, G. C.; Varma, K. S.; Hibbs, D. E.; Hursthouse, M.
B.; Malik, K. M. A. Polyhedron 1995, 14, 2623. (f) Ferguson, G.; Lough,
A. J .; Sheehan, J . P.; Spalding, T. R. Acta Crystallogr. Sect. C 1990,
46, 2390. (g) Yalpani, M.; Ko¨ster, R. Chem. Ber. 1988, 121, 1553. (h)
Das, M. K.; Mariategui, J . F.; Niedenzu, K. Inorg. Chem. 1987, 26,
3114. (i) Wu, Q. G.; Wu, G.; Brancaleon, L.; Wang, S. Organometallics
1999, 18, 2553.
(16) The possible in situ formation of triarylboroxines 4 has been
proposed; see ref 11a.
J . Org. Chem, Vol. 69, No. 15, 2004 5089

McKinley and O’Shea
TABLE 3. Cou p lin g of 4-P h en ylp h en ol w ith 6, 7, a n d 8a
entry
reagent (equiv)
base (equiv)
conversionb (%)
1
2
3
4
5
6
6 (2)
6 (2)
7 (0.66)
7 (0.66)
8 (0.66)
8 (0.66)
7
35
5
60
93
99
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
a
Reaction conditions of 1 molar equivalence of 2a and copper
b
acetate in dichloromethane at rt for 24 h. Average of two runs.
reaction of 6 in the absence of base with substrate
4-phenylphenol 2a gave a very low 7% conversion to
4-phenylbiphenyl ether 9 (Table 3, entry 1). The product
conversion improved to 35% when 1 equiv of cesium
carbonate was used in the reaction (entry 2). Similarly,
7 gave poor conversion to 9 (5%) in the absence of base
and yielded a moderate conversion of 60% when an
equivalent of cesium carbonate was employed in the
reaction (entries 3 and 4). In comparison, the reaction of
8 in the absence of base gave a good product conversion
(93%) and when the reaction was carried out using
cesium carbonate the reaction reached completion (en-
tries 5 and 6).
F IGURE 3. Views of 2,4,6-trivinylcyclotriboroxane-pyridine
complex 1 with the atomic numbering scheme. Thermal
ellipsoids drawn at 50% probability level.
These results suggest that the amine-coordinated
boroxine rings 5 have a role to play in the reaction
sequence (Scheme 2).
TABLE 4. Selected Bon d Len gth s a n d An gles for 1
bond length
Å
bond length
Å
Solu tion - a n d Solid -Sta te Str u ctu r e of 1. In solu-
tion, amine complexes of boroxines have been reported
to undergo rapid ligand dissociation-recombination pro-
cess at rt.15b-e The 11B NMR (300K, CD2Cl2) of 1 gave a
single signal with a chemical shift of 17.7 ppm implying
the magnetic equivalence of the boron centers at that
temperature and indicating a significant degree of amine
interaction with the boroxine ring. As comparison, the
chemical shifts of triphenylboroxine 7 and triphenyl-
boroxine pyridine complex 8 have been reported to be 30.4
and 20.5 ppm, respectively, at room temperature.15b In
an attempt to obtain limiting slow-exchange spectra of
1 we carried out low-temperature 11B NMR (193 K),
which resulted in significant broadening of the signal
with a peak shoulder to a lower chemical shift, but we
were unable to resolve the peaks into two definitive
B(1)-N
1.643
1.463
1.458
1.348
1.390
B(3)-O(2)
B(3)-O(3)
B(1)-C(6)
B(2)-C(8)
B(3)-C-10)
1.385
1.350
1.599
1.561
1.561
B(1)-O(1)
B(1)-O(3)
B(2)-O(1)
B(2)-O(2)
bond angle
deg
bond angle
deg
C(6)-B(1)-O(1)
C(6)-B(1)-O(3)
O(1)-B(1)-O(3)
113.43
112.70
113.20
N-B(1)-C(6)
N-B(1)-O(1)
N-B(1)-O(3)
106.54
104.59
105.4
The sum of the internal angles of boroxine ring was
719.2° indicating planarity for the ring system (sum
720°). The pyridine nitrogen to boron bond length of 1.643
Å is comparable to other reported structurally related
triaryl and trialkyl boroxine derivatives.15 The structural
consequences of the amine coordinating to a single boron
atom of the boroxine are distinct. Two of the boron
centers form a trigonal planar geometry with bond angles
ranging from 118.4° to 121.1° whereas the other is a
distorted tetrahedron with the bond angles about B(1)
varying from 104.6° to 113.4° (Table 4). An estimate of
percentage tetrahedral character of B(1) was calculated
from its six bond angles to give a value of 75%.17
Comparison of the average B-O bond lengths of the
tetrahedral B(1) and trigonal boron atoms B(2), B(3) show
that they are longer for the tetrahedral boron. Similarly
the boron to carbon bond length for tetrahedral boron
1
signals (Supporting Information). The H NMR (303K)
of 1 gave pyridine signals that were downfield by 0.21-
0.34 ppm in comparison to pyridine (Supporting Informa-
tion). These results are consistent with an amine ligand
exchange process, which appears to be general for this
class of compound.
X-ray diffraction study of a colorless crystal of 1
obtained by the slow evaporation of a toluene solution
confirmed the trivinyl-substituted boroxine ring as a
monopyridine adduct. The molecular structure revealed
the six-membered boroxine ring with one boron atom
coordinated to the nitrogen of pyridine with a distorted
tetrahedral geometry and two boron atoms with trigional
geometry (Figure 3, view A).
(17) Ho¨pfl, H. J . Organomet. Chem. 1999, 581, 129.
5090 J . Org. Chem., Vol. 69, No. 15, 2004

2,4,6-Trivinylcyclotriboroxane-Pyridine Complex
acetate was used without any modification. Pyridine was
supplied as anhydrous and used without any modification.
Dichloromethane was dried over calcium chloride and distilled
from calcium hydride.
An a lysis. 1H and 13C NMR were recorded on a 300 MHz
instrument and were referenced to tetramethylsilane (TMS).
Melting points are uncorrected.
P a r a llel Libr a r y P r oced u r e. Compound 1 (0.51 mmol),
phenol (0.77 mmol), pyridine (7.7 mmol), and copper(II) acetate
(0.77 mmol) were added to individual reaction vessels in the
parallel synthesizer and stirred at room temperature in
anhydrous dichloromethane (8 mL) for 24 h, under a calcium
chloride drying tube. Each reaction mixture was treated with
3 M aqueous ammonium acetate (2 × 10 mL) and stirring
continued for a further 30 min. Organic layers were separated
and dried over sodium sulfate, solvent was evaporated, and
the product was analyzed by GC, GC-MS, and 1H and 13C
NMR. If required, further purification by column chromatog-
raphy on alumina, eluting with CH2Cl2 was performed.
In d ivid u a l P r oced u r es. 4-Vin yloxybip h en yl (3a ). Cu-
(OAc)2 (0.54 g 2.94 mmol) was stirred at room temperature in
dry CH2Cl2 (20 mL) for 10 min. Compound 1 (0.47 g, 1.96
mmol), 4-phenylphenol (0.50 g 2.94 mmol), and pyridine (2.4
mL, 29.4 mmol) were added, and the reaction was stirred at
room temperature for 24 h. The reaction solution was passed
through an alumina column eluting with CH2Cl2 yielding the
product as a white solid (0.57 g, 98%). Mp: 52-53 °C. 1H NMR
(CDCl3) δ: 4.45 (dd, J ) 1.8, 6.2 Hz, 1H), 4.78 (dd, J ) 1.8,
13.8 Hz, 1H), 6.65 (dd, J ) 6.2, 13.8 Hz, 1H), 7.05-7.10 (m,
2H), 7.29-7.57 (m, 7H). 13C NMR (CDCl3) δ: 95.4, 117.4, 126.9,
127.1, 128.4, 128.8, 136.2, 140.5, 148.1, 156.2. IR (KBr disk)
cm-1: 1643, 1602. EI-MS: m/z 196.3.
F IGURE 4. Possible mode of transmetalation.
B(1)-C(6) is considerably longer at 1.599 Å compared to
B(2)-C(8) and B(3)-C(10) at 1.561 Å (Table 4).
From the solid- and solution-state characteristics of 1,
which are common to all substituted boroxine amine
complexes, we could speculate that the structural con-
sequences of the amine to boron coordination could
predispose such compounds to a transmetalation process.
It is known that tetracoordinate boron species are key
to a successful transmetalation step for a number of other
boronic acid coupling reactions including the Suzuki-
Miyaura18 and the thiol ester coupling19 reactions. As
such the tetrahedral boron atom of 1 could indicate a
possible reaction site with copper (Figure 3, view B).
Increased B(1)-O and B(1)-C bond lengths and reduced
C-B(1)-O bond angles around the tetrahedral boron
could facilitate an oxygen to boron coordination generat-
ing 10 which could be envisaged to possibly give rise to
an intermediate of type 11 (Figure 4).
4-Vin yloxybip h en yl (3a ). Cu(OAc)2 (0.54 g 2.94 mmol) was
stirred at room temperature in dry CH2Cl2 (20 mL) for 10 min.
Compound 1 (0.47 g, 1.96 mmol), 4-phenylphenol (0.50 g 2.94
mmol), and Cs2CO3 (0.96 g, 29.4 mmol) were added and the
reaction stirred at room temperature for 24 h. The reaction
solution was passed through an alumina column eluting with
CH2Cl2 yielding the product as a white solid 0.54 g, 93%.
Due to the complicated dimeric or oligmeric nature of
many copper complexes and the fact that it is as yet
unclear if a copper(I) or copper(II) species is the one
which initially reacts, this may be an oversimplified view
of the pathway. As alternative reaction pathways could
also be proposed, further speculation at this time is not
justified but investigations are ongoing to attempt to
further resolve the mechanistic issues of this reaction
class.
1-Br om o-2-vin yloxyben zen e (3c). Cu(OAc)2 (0.53 g, 2.93
mmol) was stirred at room temperature in dry CH2Cl2 (20 mL)
for 10 min. Compound 1 (0.47 g, 1.92 mmol), 2-bromophenol
(0.50 g, 2.93 mmol), and pyridine (2.4 mL, 29.3 mmol) were
added, and the reaction was stirred at room temperature for
24 h. The reaction mixture was washed with 3 M aqueous
ammonium acetate (2 × 40 mL), and the aqueous layers were
extracted with ethyl acetate (3 × 40 mL). The organic layers
were combined, washed with brine (2 × 40 mL), dried over
sodium sulfate, and concentrated to 20 mL. (Note: evaporation
to dryness can lead to lower yields.) The solution was diluted
with CH2Cl2 (20 mL) and passed through an alumina column
eluting with CH2Cl2 yielding the product as an oil (0.55 g,
Con clu sion s
In summary, we have described a diversity tolerant
synthetic methodology for the generation of synthetically
important aryl vinyl ethers exploiting a bench stable
vinylboronic acid equivalent as the key reagent. The role
of the organic base has been investigated and we have
shown that one equivalent of an organic amine base is
required to generate the boroxine ring, but the additional
base required can be provided by either organic amine
base or an inorganic base such as cesium carbonate.
Solid-state and solution evidence of a tetravalent boron
species is provided which could play a role in facilitating
the key steps of this reaction.
1
95%). H NMR (DMSO-d6) δ: 4.55 (dd, J ) 1.9, 6.2 Hz, 1H),
4.69 (dd, J ) 1.9, 13.6 Hz, 1H), 6.81 (dd, J ) 6.2, 13.6 Hz,
1H), 7.05-7.11 (m, 1H), 7.18-7.21 (m, 1H), 7.37-7.43 (m, 1H),
7.65-7.68 (m, 1H). 13C NMR (DMSO-d6) δ: 96.4, 113.7, 118.7,
125.5, 129.8, 133.9, 148.8, 153.6. IR (neat) cm-1: 1644, 1584.
EI-MS: m/z 198.0. Anal. Calcd for C8H8BrO: C, 48.28; H, 3.54.
Found: C, 48.58; H, 3.68.
1-Iod o-3-vin yloxyben zen e (3d ). Cu(OAc)2 (0.41 g, 2.27
mmol) was stirred at room temperature in dry CH2Cl2 for 10
min. Compound 1 (0.55 g, 2.27 mmol), 3-iodophenol (0.50 g,
2.27 mmol), and pyridine (1.8 mL, 22.7 mmol) were added, and
the reaction was stirred at room temperature for 24 h. The
reaction mixture was washed with 3 M aqueous ammonium
acetate (2 × 40 mL), and the aqueous layers were extracted
with ethyl acetate (2 × 40 mL). The organic layers were
combined, washed with brine (2 × 40 mL), dried over sodium
sulfate, and reduced to dryness. The residue was diluted with
CH2Cl2 (30 mL) and passed through an alumina column
eluting with CH2Cl2 yielding the product as an oil (0.53 g,
Exp er im en ta l Section
Ma ter ia ls. All commercially available solvents and reagents
were used as supplied unless otherwise stated. Copper(II)
(18) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (b)
Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J . Am. Chem. Soc.
1985, 107, 972. (c) Wright, S. W.; Hageman, D. L.; McClure, L. D. J .
Org. Chem. 1994, 59, 6095. (d) Matos, K.; Soderquist, J . A. J . Org.
Chem. 1998, 63, 461.
(19) (a) Liebeskind, L. S.; Srogl, J . Org. Lett. 2002, 4, 979. (b)
Liebeskind, L. S.; Srogl, J . J . Am. Chem. Soc. 2000, 122, 11260.
1
95%). H NMR (CDCl3) δ: 4.47 (dd, J ) 1.8, 6.2 Hz, 1H), 4.78
J . Org. Chem, Vol. 69, No. 15, 2004 5091

McKinley and O’Shea
(dd, J ) 1.8, 13.8 Hz, 1H), 6.55 (dd, J ) 6.2, 13.8 Hz, 1H),
6.95-7.06 (m, 2H), 7.35-7.43 (m, 2H). 13C NMR (CDCl3) δ:
96.3, 116.6, 126.2, 127.4, 131.0, 132.2, 147.5, 158.1. IR (KBr
disk) cm-1: 1643, 1580. EI-MS: m/z 246.2. Anal. Calcd for
C8H7IO: C, 39.05; H, 2.87. Found: C, 38.98; H, 2.88.
1-ter t-Bu tyl-4-vin yloxy-ben zen e (3j). Cu(OAc)2 (0.60 g,
3.33 mmol) was stirred at room temperature in dry CH2Cl2
for 10 min. Compound 1 (0.53 g, 2.21 mmol), 4-tert-butylphenol
(0.50 g, 3.33 mmol), and pyridine (2.7 mL, 33.3 mmol) were
added, and the reaction was stirred at room temperature for
24 h. The reaction mixture was washed with 3 M aqueous
ammonium acetate (2 × 40 mL), and the aqueous layers were
extracted with ethyl acetate (2 × 40 mL). The organic layers
were combined, washed with 1 M HCl (2 × 25 mL) and brine
(2 × 25 mL), dried over sodium sulfate, and reduced to dryness
yielding the product as an oil 0.47 g, 80%. 1H NMR (CDCl3) δ:
1.30 (s, 9H), 4.37 (dd, J ) 1.5, 6.0 Hz, 1H), 4.70 (dd, J ) 1.5,
13.6 Hz, 1H), 6.60 (dd, J ) 6.0, 13.6 Hz, 1H), 6.91-6.96 (m,
2H), 7.31-7.36 (m, 2H). 13C NMR (CDCl3) δ: 31.5, 34.2, 94.1,
116.7, 126.5, 127.4, 148.3, 154.4. IR (neat) cm-1: 1643, 1503.
EI-MS: m/z 176.3.
1H), 7.13-7.19 (m, 1H). 13C NMR (CDCl3) δ: 40.7, 94.7, 101.8,
104.9, 107.9, 130.1, 148.7, 152.2, 158.3. IR (KBr disk) cm-1
:
1607. EI-MS: m/z 163.3. Anal. Calcd for C10H13NO: C, 73.59;
H, 8.03; N, 8.58. Found: C, 73.28; H, 7.96; N, 8.61.
4-P h en ylbip h en yl Eth er (9). Cu(OAc)2 (0.14 g, 0.77 mmol)
was stirred at room temperature in dry CH2Cl2 for 10 min.
Triphenylboroxine-pyridine complex 8 (0.20 g, 0.51 mmol),
4-phenylphenol (0.13 g, 0.77 mmol), and pyridine (0.60 mL,
7.70 mmol) were added, and the reaction was stirred at room
temperature for 24 h. The reaction mixture was washed with
3 M aqueous ammonium acetate (2 × 40 mL), and the aqueous
layers were extracted with ethyl acetate (2 × 40 mL). The
organic layers were combined, washed with brine (2 × 25 mL),
dried over sodium sulfate, and reduced to dryness yielding a
brown solid. The solid was washed through a short plug of
alumina with dichloromethane and the filtrate reduced to yield
the product as white solid (0.17 g, 91%). Mp: 67-68 °C. 1H
NMR (CDCl3) δ: 6.99-7.15 (m, 5H), 7.31-7.46 (m, 5H), 7.53-
7.58 (m, 4H). 13C NMR (CDCl3) δ: 118.0, 122.4, 125.9, 126.0,
127.4, 127.8, 128.8, 135.3, 139.5, 155.8, 156.1. EI-MS: m/z
246.30.
Analytical data for the new compounds in Table 2.
1
4-Vin yloxyben za ld eh yd e (3g). H NMR (CDCl3) δ: 4.62
Ack n ow led gm en t. This work was supported in part
by Enterprise Ireland and the Centre for Synthesis and
Chemical Biology, UCD. We thank F. Kerins for the
crystallization of 1, UCD Crystallographic and Mass
Spectroscopy centers, and Dr. M. Tacke for helpful
discussions.
(dd, J ) 1.8, 6.0 Hz, 1H), 4.92 (dd, J ) 1.8, 13.6 Hz, 1H), 6.67
(dd, J ) 6.0, 13.6, 1H), 7.09-7.14 (m, 2H), 7.85-7.90 (m, 2H),
9.93 (s, 1H). 13C NMR (CDCl3) δ: 98.4, 116.9, 131.8, 132.2,
146.5, 161.8, 190.9. IR (KBr disk) cm-1: 1705, 1644. EI-MS:
m/z 148.1. Anal. Calcd for C9H8O2: C, 72.96; H, 5.44. Found:
C, 72.63; H, 5.46.
1-Meth oxy-2-vin yloxyben zen e (3i). 1H NMR (CDCl3) δ:
3.80 (s, 3H), 4.30 (dd, J ) 1.7, 6.0 Hz, 1H), 4.60 (dd, J ) 1.7,
13.8 Hz, 1H), 6.50 (dd, J ) 6.0, 13.8 Hz, 1H), 6.85-7.19 (m,
4H). 13C NMR (CDCl3) δ: 56.2, 94.2, 112.8, 118.9, 121.2, 124.5,
145.8, 149.5, 150.5. IR (KBr disk) cm-1: 1639. EI-MS: m/z
150.3. Anal. Calcd for C9H10O2: C, 71.98; H, 6.71. Found: C,
71.64; H, 6.70.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for new compounds 3d ,g,i,k . Literature references for
known compounds. Variable-temperature 11B NMR spectra of
1 and room-temperature comparison with pyridine. X-ray
crystallographic data of 1 as a CIF file with a view of the
crystal packing. This material is available free of charge via
the Internet at http://pubs.acs.org.
Dim eth yl(3-vin yloxyph en yl)am in e (3k). 1H NMR (CDCl3)
δ: 2.94 (s, 6H), 4.37 (dd, J ) 0.7, 6.0 Hz, 1H), 4.72 (dd, J )
0.7, 13.3, 1H), 6.35-6.46 (m, 3H), 6.63 (dd, J ) 6.0, 13.3 Hz,
J O049314L
5092 J . Org. Chem., Vol. 69, No. 15, 2004