Synthesis of Polycyclic Aromatic Hydrocarbons by the Pd-Catalyzed Annulation of Alkynes

Full text of DOI:10.1021/jo9712557

7
536
J . Org. Chem. 1997, 62, 7536-7537
Syn th esis of P olycyclic Ar om a tic
Hyd r oca r bon s by th e P d -Ca ta lyzed
An n u la tion of Alk yn es
organic iodide or triflate, 1.1 or 2.0 equiv of the alkyne,
mol % of Pd(OAc)
, 2 equiv of NaOAc, 1 equiv of LiCl
in DMF at 100 °C. P r oced u r e B: 1 equiv of the organic
5
2
iodide or triflate, 1.1 or 2.0 equiv of the alkyne, 5 mol %
2 4
of Pd(OAc) , 2 equiv of NaOAc, 3 equiv of n-Bu NCl in
Richard C. Larock,* Mark J . Doty,
Qingping Tian, and J ohn M. Zenner
DMF at 100 °C. The procedure used for these reactions
is strongly influenced by the structure of the alkyne. In
general, procedure B works better for diarylacetylenes
and silylacetylenes, while procedure A is more successful
when alkyl-substituted acetylenes are used. The gener-
ality of this process has been demonstrated by the
annulation of a variety of functionalized alkynes using a
number of functionally substituted aryl or vinylic halides
or triflates (Table 1).
Department of Chemistry, Iowa State University,
Ames, Iowa 50011
Received J uly 11, 1997
Palladium-catalyzed annulation has recently proven
useful as a means of forming polycyclic aromatic hydro-
1
carbons. For example, Dyker has synthesized disubsti-
5
As with our previous work, this annulation process
tuted acenaphthylene derivatives from 1,8-diiodonaph-
thalene and alkynes in the presence of a palladium
works best for alkynes containing hindered groups, such
as aryl, tert-butyl and trialkylsilyl groups. 1-Phenyl-2-
2
catalyst, while Grigg has formed 7,8-diphenylacenaph-
(triethylsilyl)acetylene reacts with 2-iodobiaryls to give
thylene by the palladium-catalyzed coupling of 1-io-
donaphthalene and diphenylacetylene. Substituted
phenanthrenes have also been synthesized using pal-
the desired 9,10-disubstituted phenanthrenes in fair
yields (entries 4-6). The relatively low yields obtained
in reactions employing silylacetylenes is most likely due
to competing desilylation of the alkyne and subsequent
palladium-catalyzed coupling of the aryl iodide to the
terminal acetylene affording the corresponding diary-
lacetylene. Regioselectivity in the annulation of unsym-
metrical acetylenes using biaryls was low and seemed
to be influenced by the steric bulk of the alkyne substit-
uents, as well as the substituents on the biaryl (entries
ladium methodology.3 For example, Heck reported in
,4
3b
1
987 the formation of 9,10-diphenylphenanthrene in 14%
yield by the reaction of 2-iodobiphenyl, diphenylacetylene,
mol % Pd(OAC) , 4 mol % PPh , and Et N in CH NO
for 2 days at 100 °C (eq 1). Our own interest in the
2
2
3
3
3
2
5
and 6).6 Modest regioselectivity was observed in the
annulation involving 2-(2′-iodophenyl)naphthalene (entry
).
Vinylic halides and triflates bearing aryl groups in the
7
synthesis of hetero- and carbocycles by the Pd-catalyzed
annulation of internal acetylenes (eq 2) led us to further
5
2-position also serve as efficient substrates in this alkyne
annulation process. A number of 9,10-disubstituted-
1
,2,3,4-tetrahydrophenanthrenes have been prepared in
good yields by the palladium-catalyzed annulation of
internal alkynes using 1-iodo-2-phenylcyclohexene or
2
-phenyl-1-cyclohexenyl triflate (entries 8-13). In con-
trast to the annulation process using biaryls, these
annulations proceed with high regioselectivity. The
regiochemistry of the product shown in entries 10 and
investigate this reaction. Herein we report improved
reaction conditions, which extend the Heck process to a
wide variety of internal acetylenes and 2-iodobiaryls, as
well as vinylic halides and triflates bearing aryl groups
in the 2-position. The resulting methodology accom-
modates a variety of structurally and functionally diverse
aryl and vinylic substrates and affords the anticipated
annulation products in moderate to excellent yields.
We initiated our studies on the reaction of 2-iodobi-
phenyl and diphenylacetylene (eq 1) and found that
under conditions similar to those used in our palladium-
catalyzed synthesis of isocoumarins,5b 9,10-diphenyl-
phenanthrene was obtained in 89% yield. Further
optimization with a variety of internal alkynes has led
to the development of two general procedures to affect
this annulation process. P r oced u r e A: 1 equiv of the
1
1 of Table 1 has been confirmed by a 2D NOESY
7
experiment. This regioselectivity is consistent with our
previous acetylene annulation work in which the aryl or
vinylic group adds to the less hindered end of the alkyne.
5
Other cyclic vinylic iodides and triflates have also been
employed in this annulation process. For example, 5,6-
diphenyl-7H-benzo[c]fluoren-7-one was obtained in 54%
yield from the reaction of 2-iodo-3-phenylindenone and
diphenylacetylene (entry 14).
Acyclic vinylic iodides and triflates have also been
examined. No annulation products were obtained when
(Z)-1-iodo-2-phenylethylene was used as a substrate,
perhaps due to â-hydride elimination from the presumed
initial vinylic palladium intermediate. On the other
hand, 2-iodo-1,1-diphenylethylene, which has no â-hy-
drogens, affords the expected products (entries 15 and
(
1) Dyker, G. J . Org. Chem. 1993, 58, 234-238.
1
6), although only modest regiospecificity was observed
(
2) Grigg, R.; Kennewell, P.; Teasdale, A.; Sridharan, V. Tetrahedron
Lett. 1993, 34, 153-156.
3) (a) Dyker, G.; Kellner, A. Tetrahedron Lett. 1994, 35, 7633-7636.
b) Wu, G.; Rheingold, A.; Geib, S. J .; Heck, R. F. Organometallics 1987,
, 1941-1946.
4) For a general review of phenanthrene synthesis, see: Floyd, A.
J .; Dyke, S. F.; Ward, S. E. Chem. Rev. (Washington, D.C.) 1976, 76,
when 3,3-dimethyl-1-phenyl-1-butyne was used as the
substrate. The low regioselectivity may be due to the low
steric demand of the hydrogen at the R-position of the
initial vinylic palladium intermediate. A hydrogen at
this position may be too small to control the regioselec-
(
(
6
(
5
09.
(
5) (a) Larock, R. C.; Yum, E. K. J . Am. Chem. Soc. 1991, 113, 6689-
6
690. (b) Larock, R. C.; Yum, E. K.; Doty, M. J .; Sham, K. K. C. J .
(6) Spencer, J .; Pfeffer, M.; Kyritsakas, N.; Fischer, J . Organome-
tallics 1995, 14 (4), 2214-2224.
(7) Keener, J .; Meier, B. H.; Bachmann, P.; Ernst, R. R. J . Chem.
Phys. 1979, 71, 4546-4553.
Org. Chem. 1995, 60, 3270-3271. (c) Larock, R. C.; Doty, M. J .; Cacchi,
S. J . Org. Chem. 1993, 58, 4579-4583. (d) Larock, R. C.; Yum, E. K.
Manuscript in preparation.
S0022-3263(97)01255-3 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 22, 1997 7537
Ta ble 1. Syn th esis of P olycyclic Ar om a tics via P d -Ca ta lyzed Ca r boa n n u la tion of In ter n a l Acetylen es.
tivity of the addition of the vinylic palladium to the
internal alkynes. As expected, 2-iodo-1,1-diphenylpro-
pene, having a larger methyl group as an R-substituent,
reacted with 3,3-dimethyl-1-phenyl-1-butyne to afford a
single regioisomer in 46% yield (entry 17).
acetylenes or hindered alkyl- or silylacetylenes. Func-
tionalization of the biaryl seems to have little effect on
the product yields. However, surprisingly low regiose-
lectivity is observed in the alkyne insertion of such
biaryls, while vinylic starting materials exhibit signifi-
cantly enhanced regioselectivity. This methodology pro-
vides an exceptionally efficient route to a wide variety of
substituted polycyclic aromatic hydrocarbons from readily
available starting materials, affording the products in
moderate to excellent yields. The use of readily available
silyl-substituted alkynes provides silyl aromatics readily
functionalized further.
On the basis of the profound difference in the rate of
annulation onto the MeO- versus the CF -substituted
3
aromatic ring (Table 1, entries 2 and 3), as well as the
preference of 2-(2′-iodophenyl)naphthalene for annulation
in the 1-position (Table 1, entry 7), we tentatively propose
a process involving oxidative addition of the organic
halide or triflate to produce an organopalladium inter-
mediate, which rapidly inserts the acetylene to produce
a vinylic palladium species. This species in turn under-
goes electrophilic aromatic substitution, followed by
reductive elimination of the observed product to regener-
ate Pd(0) An alternative mechanistic route involves
oxidative addition of the neighboring aryl C-H bond to
the vinylic palladium intermediate generating a Pd(IV)
species, followed by reductive elimination of the product
and HX, thus regenerating Pd(0) (see Supporting Infor-
mation for mechanisms). No products of multiple alkyne
insertion have been observed.
Ack n ow led gm en t . We gratefully acknowledge
Procter & Gamble Corp., as well as the U.S. Department
of Education (GAANN Fellowship), for financial support
in the form of fellowships. In addition, we thank the
donors of the Petroleum Research Fund, administered
by the America Chemical Society, for partial support of
this research. Thanks are also extended to J ohnson
Matthey, Inc. and Kawaken Fine Chemicals Co., Ltd.
for donating palladium acetate.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
The palladium-catalyzed carboannulation of internal
acetylenes using biaryls or styrenyl halides or triflates
is a process which is quite general in scope. A fair variety
of internal alkynes can be annulated using this chemis-
try, although the reaction is most general for aryl
tal procedure, a mechanistic representation of the Pd-catalyzed
1
annulation, spectroscopic characterization, and copies of H
and 13C NMR spectra (36 pages).
J O9712557