Zhou and Larock
(compare entries 8, 9, and 6). Only when a 1:1 mixture of
DMSO and H2O was employed did the yield actually drop below
the yield observed when using pure DMSO (entry 10). A solvent
consisting of 1:4 DMSO/H2O provided only a 20% yield (entry
11). The lower yields possibly arise from solubility problems
with the organic substrates in such aqueous solvent systems.
The presence of a base is known to facilitate the homocoupling
of vinylic and arylboronic acids.11,12 However, adding a base
suppresses formation of the tetrasubstituted olefin (entries 12
and 13). Only a 42% yield was obtained when 1 equiv of KOAc
was employed as the base (entry 12), and the addition of K2-
CO3 afforded an even lower yield (entry 13). Only a trace of
the desired tetrasubstituted olefin was obtained when an
arylboronic ester, 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaboro-
lane, was used instead of phenylboronic acid (entry 14). Without
the molecular O2 oxidant, the reaction is sluggish (entry 15).
Like other Pd(II)-catalyzed aerobic oxidation reactions,9 the
Pd source is critical for the success of this chemistry. Pd(OAc)2
is superior to any other Pd catalyst so far tested. Much lower
yields of the desired product were obtained using Pd2(dba)3 or
Pd(PPh3)4 (entries 16 and 17). The presence of chloride ion
greatly suppresses the reaction, and only a trace of the desired
product was obtained when PdCl2(PPh3)2 or PdCl2 was used as
the catalyst (entries 18 and 19). Similar observations have been
made in other Pd(II)-catalyzed aerobic oxidation reactions run
in DMSO.9
wide variety of internal alkynes have been screened (entries
5-17). Aldehyde-, alcohol-, ester- and TMS-containing alkynes
have also been successfully employed without protection, and
the chemistry provides the desired tetrasubstituted olefins in
good yields (entries 6-12). When the acetal-containing phe-
nylpropynal diethyl acetal was employed, the desired tetrasub-
stituted acetal-containing olefin was initially formed as observed
by GC-MS. However, the acetal-containing olefin was not stable
on silica gel, and the corresponding aldehyde 7 was obtained
in an 80% yield after column chromatography (entry 8). The
electron-rich and sterically bulky alkynes 1-trimethylsilyl-1-
propyne and 4,4-dimethyl-2-pentyne failed to produce any of
the desired tetrasubstituted olefins (entries 13 and 14). The
terminal alkyne, phenylacetylene, fails to provide the desired
trisubstituted product, possibly as a result of multiple insertions
of the alkyne leading to oligomerization (entry 15). The
relatively electron-poor diethyl acetylenedicarboxylate has been
successfully employed, producing the desired olefin in a 55%
yield (entry 16). The relatively electron-poor and sterically
hindered alkyne 3-phenyl-1-(2,4,5-trimethoxyphenyl)propynone
produced the desired olefin 13 in a 66% yield (entry 17). A
higher yield of the desired product is obtained with the
introduction of an electron-withdrawing nitro group into the
aromatic ring of 1-phenyl-1-butyne (compare entries 18 and 1).
Thus, an excellent 90% yield is obtained when 1-(4-nitrophenyl)-
1-butyne is allowed to react with p-tolylboronic acid (entry 18).
This reaction involves the clean cis addition of the two aryl
groups from the arylboronic acid to the alkyne. The structure
of product 14 has been determined by examining its NOESY
H-H interactions.14
When 1-(4-nitrophenyl)-1-butyne is used as the alkyne, a wide
variety of arylboronic acids have been successfully employed
in this process. Electron-rich and electron-neutral arylboronic
acids work quite well in this chemistry and afford the desired
tetrasubstituted olefins in good yields (entries 18-24). It is
noteworthy that acetal-containing arylboronic acids work quite
well, and the desired acetal-containing tetrasubstituted olefins
have been obtained in good yields (entries 20 and 21). However,
electron-poor arylboronic acids afford significantly lower yields
of the tetrasubstituted olefins. Only a 53% yield of the desired
tetrasubstituted olefin was obtained when 3,5-difluorophenyl-
boronic acid was employed (entry 25). None of the desired
tetrasubstituted olefin was observed when 4-nitrophenylboronic
acid was utilized (entry 26). Relatively low yields were obtained
when the sterically hindered arylboronic acids 2-methylphenyl-
boronic acid and 2-methoxyphenylboronic acid were employed
(entries 27 and 28). When E-2-phenylvinylboronic acid was
utilized, only a complex mixture was obtained after column
chromatography, possibly because the triene product is not stable
and decomposes (entry 29). None of the desired product was
observed when 2-thienylboronic acid was employed (entry 30).
It is interesting that no 2,2′-bithiophene side product was
observed either. It is quite possible that the stable S-chelating
vinylpalladium intermediate forms, tying up the palladium
catalyst and killing the reaction.
It is noteworthy that trisubstituted olefins are not observed
in our process, despite the fact that trisubstituted olefins have
been reported as the major products in the Rh-,5 Ni-,6 or Pd-
catalyzed7 additions of arylboronic acids to internal alkynes. A
50% yield of the desired tetrasubstituted olefin was obtained
when only 2 equiv of phenylboronic acid was employed (entry
20). Thus, the optimal, very simple, “base free” procedure
described in entry 7 of Table 1 has been chosen as our “optimal”
procedure and employed for the synthesis of a wide variety of
tetrasubstituted olefins.13
Scope and Limitations. As indicated in Table 2, this
approach to tetrasubstituted olefins is quite versatile (eq 4). The
reaction proceeds well using 1-phenyl-1-propyne or 1-phenyl-
1-hexyne (entries 2 and 3).
The reaction of p-tolylboronic acid and 1-phenyl-1-butyne
provides a slightly higher yield than that of phenylboronic acid
(compare entries 1 and 4). When p-tolylboronic acid is used, a
(11) For the homocoupling of boronic acids or esters in the presence of
a base, see: (a) Miyaura, N.; Suzuki, A. Main Group Met. Chem. 1987,
10, 295. (b) Campi, E. M.; Jackson, W. R.; Marcuccio, S. M.; Naeslund,
C. G. M. J. Chem. Soc., Chem. Commun. 1994, 2393. (c) Gillmann, T.;
Weeber, T. Synlett 1994, 649. (d) Song, Z. Z.; Wong, H. N. C. J. Org.
Chem. 1994, 59, 33. (f) Wong, M. S.; Zhang, X. L. Tetrahedron Lett. 2001,
42, 4087. (g) Koza, D. J.; Carita, E. Synthesis 2002, 2183. (h) Falck, J. R.;
Mohapatra, S.; Bondlela, M.; Venkataraman, S. K. Tetrahedron Lett. 2002,
43, 8149. (i) Lei, A.; Zhang, X. Tetrahedron Lett. 2002, 43, 2525.
(12) For the homocoupling of boronic acids or esters in the absence of
a base, see: (a) Moreno-Man˜as, M.; Pe´rez, M.; Pleixats, R. J. Org. Chem.
1996, 61, 2346. (b) Yoshida, H.; Yamaryo, Y.; Ohshita, J.; Kunai, A.
Tetrahedron Lett. 2003, 44, 1541.
(13) Entry 7 was chosen as the “optimal” conditions for exploring the
scope of this chemistry because of the convenience of product purification.
However, the stoichiometry is not necessarily the best stoichiometry from
an atom-economical view. Considering the availability of the starting alkynes
and boronic acids, one can certainly run the reaction using other stoichi-
ometries for better use of all reagents.
Only a trace of the desired tetrasubstituted olefin is observed
from the GC-MS analysis of the crude products when electron-
rich dialkylacetylenes, like 4-octyne, are employed. A highly
substituted 1,3-diene formed from 2 equiv of boronic acid and
2 equiv of alkyne was obtained instead. Both electron-rich and
electron-poor arylboronic acids afford analogous 1,3-dienes in
(14) See Supporting Information in ref 10 for detailed information.
3186 J. Org. Chem., Vol. 71, No. 8, 2006