C-C-Bond Formation by the Palladium-Catalyzed Cycloisomerization/Dimerization of Terminal Allenyl Ketones: Selectivity and Mechanistic Aspects

Article abstract of DOI:10.1021/jo970837l

The scope of the palladium-catalyzed cyclization/dimerization of terminal allenyl ketones 1 to the 2,4-disubstituted furans 3 has been investigated. Simplified and improved conditions almost exclusively provided the dimer 3, accompanied by only traces of the easily separable monomer 2. The formation of an isomer of 3, the unconjugated ketone 4, was completeley suppressed. Under these mild conditions, besides the normal functional group tolerance known for palladium-catalyzed reactions, an interesting selectivity was observed with functional groups that are known to react either in palladium-catalyzed reactions or reactions catalyzed by other transition-metals. Thus aryl halides, terminal alkynes, 1,6-enynes, and α-allenic alcohols were tolerated. In the latter example the selective reaction of only one out of two different allenes was achieved. Mechanistic investigation indicated a Pd(II)/Pd(IV)-cycle involving palladium(II)-γ-alkoxyvinylcarbene and furylpalladium(IV) hydride intermediates, although a second pathway for the formation of the dimer 3 which also involves Pd(IV)-intermediates like the 3,4-dimethylenepalladacyclopentane 23 and the 3-methylenepalladacyclobutane-like structure 15 (respectively 25) could not completely be excluded.

Full text of DOI:10.1021/jo970837l

J . Org. Chem. 1997, 62, 7295-7304
7295
C-C-Bon d F or m a tion by th e P a lla d iu m -Ca ta lyzed
Cycloisom er iza tion /Dim er iza tion of Ter m in a l Allen yl Keton es:
Selectivity a n d Mech a n istic Asp ects
A. Stephen K. Hashmi,*,† Thorsten L. Ruppert, Thomas Kno¨fel, and J an W. Bats
Institut fu¨r Organische Chemie der Freien Universita¨t Berlin, Takustrasse 3, D-14195 Berlin, Germany
Received May 9, 1997X
The scope of the palladium-catalyzed cyclization/dimerization of terminal allenyl ketones 1 to the
2,4-disubstituted furans 3 has been investigated. Simplified and improved conditions almost
exclusively provided the dimer 3, accompanied by only traces of the easily separable monomer 2.
The formation of an isomer of 3, the unconjugated ketone 4, was completeley suppressed. Under
these mild conditions, besides the normal functional group tolerance known for palladium-catalyzed
reactions, an interesting selectivity was observed with functional groups that are known to react
either in palladium-catalyzed reactions or reactions catalyzed by other transition-metals. Thus
aryl halides, terminal alkynes, 1,6-enynes, and R-allenic alcohols were tolerated. In the latter
example the selective reaction of only one out of two different allenes was achieved. Mechanistic
investigation indicated a Pd(II)/Pd(IV)-cycle involving palladium(II)-γ-alkoxyvinylcarbene and
furylpalladium(IV) hydride intermediates, although a second pathway for the formation of the dimer
3 which also involves Pd(IV)-intermediates like the 3,4-dimethylenepalladacyclopentane 23 and
the 3-methylenepalladacyclobutane-like structure 15 (respectively 25) could not completely be
excluded.
In tr od u ction
of allenes in organic synthesis.5 Among them is Mar-
shall’s6 discovery that allenyl ketones7 1 can selectively
be rearranged into furans 2 under mild conditions by
Rh(I) or Ag(I) catalysts. This was a landmark in the area
of transition-metal-catalyzed furan synthesis.
While alkynes are frequently used in transition-metal-
catalyzed cross-coupling, addition, cycloaddition, or cy-
cloisomerization reactions,1 the use of the isomeric allenes
is much less popular. This probably originates from the
fact that many transition-metal fragments, which cata-
lyze such reactions, also cause an unspecific oligomer-
ization2,3 or a polymerization4 of allenes. During the last
years improved catalyst-systems and milder conditions
have been developed. This led to an increase in the use
Similar isomerizations had been observed several years
before in flash vacuum thermolysis reactions of allenyl
ketones by J ullien8 and Huntsman,9 but only the transi-
tion-metal-catalysis made possible this transformation
with highly functionalized, nonvolatile substrates.10 This
principle was applied by Marshall in efforts to synthesize
macrocyclic furan marine natural products.6 The impor-
tance of the furan moiety, which is frequently found in
natural products and in important pharmaceuticals as
well as in flavoring, aroma, and fragrance compounds11
and is often used as building block in organic synthesis,
has always been the driving force for the numerous
synthetic efforts for the synthesis of furans.11,12
† Present address: Institut fu¨r Organische Chemie der J ohann
Wolfgang Goethe-Universita¨t, Marie-Curie-Strasse 11, D-60439 Frank-
furt am Main, Germany.
X Abstract published in Advance ACS Abstracts, September 15, 1997.
(1) (a) Schore, N. E. Chem. Rev. 1988, 88, 1081-1119. (b) Keim,
W.; Behr, A.; Ro¨per, M. In Comprehensive Organometallic Chemistry;
Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon Press:
Oxford, 1982; vol. 8, pp 371-462. (c) J olly, P. W. Ibid. pp 649-670. (d)
Chan, D. M. T. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Paquette, L. A., Eds; Pergamon Press: Oxford, 1991; vol.
5, pp 271-314. (e) Schore, N. E. Ibid. pp 1037-1064; 1129-1162. (f)
Wulff, W. D. Ibid. pp 1065-1113. (g) Negishi, E. Ibid. pp 1163-1184.
(2) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis;
J ohn Wiley & Sons: New York, 1984.
(3) For transition-metal complexes of allenes, see: (a) J olly, P. W.;
Wilke, G. The Organic Chemistry of Nickel; Academic Press: New York,
1975. (b) J olly, P. W. ref 1b, vol. 8; pp 613-647. (c) Shaw, B. L.;
Stringer, A. J . Inorg. Chem. Acta Rev. 1973, 7, 1-10. (d) Bowden, F.
L.; Giles, R. Coord. Chem. Rev. 1976, 20, 81-106. (e) Erker, G. In
Houben-Weyl; Falbe, J ., Ed.; Thieme: Stuttgart, 1986; vol. E18, pp
843-891 (specific pp 870-873).
(4) (a) Shier, G. D. J . Organomet. Chem. 1967, 10, P15-P17. (b)
Coulson, D. R. J . Org. Chem. 1972, 37, 1253-1254; 1973, 38, 1483-
1490. (c) Siegel, H.; Hopf, H.; Germer, A.; Binger, P. Chem. Ber. 1978,
111, 3112-3118. (d) Kunakova, R. V.; Sidorova, V. V.; Dzhemilev, U.
M. Izv. Akad. Nauk SSSR, Ser. Khim. 1985, 2624-2626; Chem. Abstr.
1986, 105, 171780v.
(5) (a) Trost, B. M.; Tour, J . M. J . Am. Chem. Soc. 1988, 110, 5231-
5233. (b) Trost, B. M.; Matsuda, K. J . Am. Chem. Soc. 1988, 110, 5233-
5235. (c) Munz, C.; Stephan, C.; tom Dieck, H. J . Organomet. Chem.
1990, 395, C42-C46. (d) Trost, B. M.; Kottirsch, G. J . Am. Chem. Soc.
1990, 112, 2816-2818. (e) Ma, S.; Negishi, E. J . Org. Chem. 1994, 59,
4730-4732. (f) Ma, S.; Negishi, E. J . Am. Chem. Soc. 1995, 117, 6345-
6357. (g) Kent, J . L.; Wan, H.; Brummond, K. M. Tetrahedron Lett.
1995, 36, 2407-2410. (h) Trost, B. M.; Gerusz, V. J . J . Am. Chem.
Soc. 1995, 117, 5156-5157. (i) Yamamoto, Y.; Al-Masum, M.; Fujiwara,
N. J . Chem. Soc., Chem. Commun. 1996, 381-382.
(6) (a) Marshall, J . A.; Robinson, E. D. J . Org. Chem. 1990, 55,
3450-3451. (b) Marshall, J . A.; Wang, X. J . Org. Chem. 1991, 56, 960-
969. (c) Marshall, J . A.; Wang, X. J . Org. Chem. 1992, 57, 3387-3396.
(d) Marshall, J . A.; Bartley, G. S. J . Org. Chem. 1994, 59, 7169-7171.
(e) Marshall, J . A.; Wallace, E. M.; Coan, P. S. J . Org. Chem. 1995,
60, 796-797. (f) Marshall, J . A.; Sehon, C. A. J . Org. Chem. 1995, 60,
5966-5968.
(7) (a) Huche´, M. Tetrahedron 1980, 36, 331-342. (b) Larock, R.
C.; Chow, M.-S.; Smith, S. J . J . Org. Chem. 1986, 51, 2623-2624. (c)
Bernard, D.; Doutheau, A.; Gore, J . Tetrahedron 1987, 43, 2721-2732.
(8) J ullien, J .; Pechine, J . M.; Perez, F.; Piade, J . J . Tetrahedron
1982, 38, 1413-1416.
(9) Huntsman, W. D.; Yin, T.-K. J . Org. Chem. 1983, 48, 3813-3814.
(10) The reverse transformation of furans to allenyl ketones can be
achieved by the photorearrangement of some silylfurans, see: Barton,
T. J .; Hussmann, G. P. J . Am. Chem. Soc. 1983, 105, 6316-6318.
(11) Danheiser, R. L.; Stoner, E. J .; Koyama, H.; Yamashita, D. S.;
Klade, C. A. J . Am. Chem. Soc. 1989, 111, 4407-4413 and literature
cited therein.
S0022-3263(97)00837-2 CCC: $14.00 © 1997 American Chemical Society

7296 J . Org. Chem., Vol. 62, No. 21, 1997
Hashmi et al.
Ta ble 1. Rea ction of 1a w ith th e TCP CTF E Ca ta lyst in
C6D6
Marshall’s furan synthesis attracted our interest, since
many questions concerning the mechanism arose. Seven
months after we started our investigation, Marshall
published his own results6d on the mechanism of the
reaction, which were in accord with our findings. Fur-
thermore we observed that Cu(I)-, Rh(II)-, Ru(II)-, and
Pd(II)-catalyzed the cycloisomerization of allenyl ketones
to furans as well. In the case of terminal allenyl ketones,
Pd(II) caused a cyclization/dimerization, leading to the
2,4-disubstituted furans 3.13
[1a ]
(mol/L)
%
ratio
isolated yield
entry
catalyst
2a :3a :4a a
of 3a + 4a ,b %
1
2
3
4
5
6
7
0.25
0.50
1.00
2.00
4.19
7.47
11.4c
0.40
0.20
0.10
0.10
0.10
0.05
0.05
1.0:0.9:0.5
1.0:1.2:0.3
1.0:1.5:0.3
1.0:1.7:0.3
1.0:2.2:0.2
1.0:2.5:0.1
1.0:7.4:traces
55
54
59
59
64
63
76
a
b
By 1H NMR. 2a was too volatile to be separated from the
solvent. 3a and 4a could be separated by HPLC only. c Neat 1a .
[RuCl2(CO)3]2,16 and Pd catalysts were active. The latter
turned out to be most effective.13 Interestingly, in
addition to the expected 2-methylfuran (2a ) two new
products 3a and 4a were formed with the Pd catalysts.17
Initially, Trost’s TCPCTFE-modification18 of Maitlis’ pal-
ladol catalyst19 was most effective for the formation of
the dimers 3a and 4a .
The latter reaction-pathway combines a C-O bond
formation, a C-H bond breaking and formation, ands
different from Marshall’s cycloisomerizationsa C-C bond
formation. The importance of such reactions is docu-
mented by the fact that the synthesis of furans with
certain substitution patterns, i. e. bearing substituents
at both the 3 and 4 positions, is still a topic in organic
synthesis.12a,14
Here we report simplified and improved conditions for
the selective formation of 3, describe interesting chemose-
lectivities, and discuss mechanistic aspects.
Resu lts a n d Discu ssion
1. In itia l Obser va tion . Several late transition-metal
complexes and some Lewis-acids were tested toward their
ability to cycloisomerize 1a 15 in benzene. Different from
Lewis-acids like AlCl3, ZnBr2, and Hg(OAc)2, transition-
metals in the form of CuCl, AgNO3, Rh2(OAc)4,
A HETCOR and a 1-D INADEQUATE experiment
were necessary to verify the structure of 3a .13,20 Mean-
while the structural assignment has been confirmed by
X-ray analysis of two crystalline derivatives (see below).
Since the new products 3a and 4a were dimers of 1a ,
it should be possible to shift the product ratio in favor
of 3a and 4a by increasing the concentration of 1a . The
results obtained with TCPCTFE at different concentrations
are shown in Table 1. With higher concentrations of 1a
the yields of 3a and 4a went up. These conversions were
easily possible on a preparative scale (11.2 mmol in Table
1, entry 6). But this procedure was synthetically unsat-
isfying, since even with neat 1a only a ratio of 1.0:7.4
was achieved (Table 1, entry 7), and the option to use
neat substrates only exists for liquids with relatively low
viscosity. Furthermore, with the Pd(II) catalysts (more
than 1100 turnovers, Table 1, entry 6) much higher
substrate to catalyst ratios than with the Ag(I) (5.6
turnovers)6c or the Rh(I) catalysts (8.5 turnovers)6a were
possible.21
(12) (a) Yang, Y.; Wong, H. N. C. J . Chem. Soc., Chem. Commun.
1992, 1723-1725. (b) Maier, M. E. Nachr. Chem. Tech. Lab. 1993, 41,
696-704. (c) Gilchrist, T. L. Contemp. Org. Synth. 1994, 1, 205-217.
(d) Shipman, M. Contemp. Org. Synth. 1995, 2, 1-17.
(13) Hashmi, A. S. K. Angew. Chem. 1995, 107, 1749-1751; Angew.
Chem., Int. Ed. Engl. 1995, 34, 1581-1583.
(14) Bailey, T. R. Synthesis 1991, 242-243. Da Silva, G. V. J .;
Pelisson, M. M. M.; Constantino, M. G. Tetrahedron Lett. 1994, 35,
7327-7330. Trost, B. M.; McIntosh, M. C. J . Am. Chem. Soc. 1995,
117, 7255-7256. Hiroya, K.; Ogasawara, K. Synlett 1995, 175-176.
Craig, D.; Etheridge, C. J . Tetrahedron 1996, 52, 15289-15310. Ye,
X.-S.; Yu, P.; Wong, H. N. C. Liebigs Ann./ Recueil 1997, 459-466.
Wong, M. K.; Leung, C. Y.; Wong, H. N. C. Tetrahedron 1997, 53,
3497-3512.
(15) Buono, G. Synthesis 1981, 872-872.
(16) Like TCPC (see ref 18) this complex catalyses enyne-methathe-
sis: Chatani, N.; Morimoto, T.; Muto, T.; Murai, S. J . Am. Chem. Soc.
1994, 116, 6049-6050.
(17) All new compounds were characterized by NMR, infrared, mass
spectroscopic data, high-resolution mass spectra in most cases and by
elemental analyses. See Supporting Information.
(18) TCPCTFE
) tetrakis[(2,2,2-triflouroethoxy)carbonyl]pallada-
cyclopentadiene, see: Trost, B. M.; Trost, M. K. J . Am. Chem. Soc.
1991, 113, 1850-1852.
2. Th e Aceton e/TCP CTF E-System . For further im-
provement of the yield of 3a the solvent dependency was
crucial. The product ratio obtained in different solvents
is depicted in Table 2. While most of the solvents gave
results comparable to C6D6, acetone provided 3a as the
major product; the isomer 4a was not observed any more
(Table 2, entry 4). In all of these experiments a super-
imposition of the solvent dependency of the ratio of
2a :3a :4a and an increasing preference of the monomer
(19) Moseley, K.; Maitlis, P. M. J . Chem. Soc., Chem. Commun.
1971, 1604-1605.
(20) The 1H NMR of 3a contained singlets only. Another compound
that would provide comparable 1H and 13C NMR spectra, would be a
R-alkylidene pyran formed by Diels-Alder reaction and subsequent
double bond migration:
For a related [4 + X] reaction of carbon monoxide (X ) 1) instead of
an allenic double bond (X ) 2), see: Sigman, M. S.; Kerr, C. E.; Eaton,
B. E. J . Am. Chem. Soc. 1993, 115, 7545-7546. Sigman, M. S.; Eaton,
B. E.; Heise, J . D. Kubiak, C. P. Organometallics 1996, 15, 2829-2832.
But NOE-data and UV-spectra do not agree with this structure, too.
(21) We also tried the Ag(I)-catalyst with our substrates and were
able to achieve
a turnover-number of 100, but under the same
conditions as applied for the Pd-catalysts the reactions needed 1-2
weeks.

Cycloisomerization/Dimerization of Terminal Allenyl Ketones
J . Org. Chem., Vol. 62, No. 21, 1997 7297
Ta ble 2. Rea ction of 1a w ith th e TCP CTF E Ca ta lyst in
Differ en t Solven tsa
a complex product mixture with PdCl2(MeCN)2. The
Lewis-acidity of PdCl2 in acetone is too strong but
TCPCTFE, which is less Lewis-acidic, still shows a selec-
tive reaction in acetone. A further discussion of these
solvent effects will be given in the mechanistic section.
4. Oth er Su bstr a tes. So far acetylallene (1a ) was
used as a test system. The other allenyl ketones were
conveniently prepared by two methods: Either by the
direct addition of allenylmagnesium bromide 6 to esters
5 at -78 °C25 or by the addition of 6 to aldehydes 7
followed by a Dess-Martin oxidation of the homopro-
pargylic alcohols 8.26
ratio
isolated yield
entry
solvent
pentane
2a :3a :4a b
of 3a + 4a ,c %
1
2
3
4
5
6
6
7
8
1.0:2.9:0.3
1.0:1.4:0.4
1.0:2.5:0.2
1.0:8.8:0.3
1.0:4.2:traces
1.0:7.1:traces
1.0:1.9:0.2
1.0:1.7:0.2
d
65
60
63
86
74
63
60
59
-
CDCl3
ethyl acetate
acetone-d6
ethanol
methanol
THF
diethyl ether
DMSO
a
At 1 M concentration and with 0.1% of catalyst, compare Table
1, entry 3. By 1H NMR. c 3a and 4a could be separated by HPLC
only. Reaction inhibited. Only some unidentified material was
b
d
formed.
Ta ble 3. Rea ction of 1a w ith Differ en t Tr a n sition -Meta l
a
Ca ta lysts in Aceton e-d 6
ratio of
isolated yield
entry
catalyst
1.0% CuCl
2a :3a :4a b
of 3a + 4a ,c %
1
2
3
4
6
7
8
1.0:traces:0d,e
1.0:0:0d,e
-
-
1.0% AgNO3
1.0% Rh2(OAc)4
1.0:0:0e
-
0.5% [Ru(Cl)2(CO)3]2 1.0:0:0d
-
0.1% TCPCTFE/PPh3
f
-
0.1% TCPCTFE
1.0:8.8:0.3
1.0:2.4:0.1
86
71
0.4% Pd(OAc)2
a
At 1 M concentration. Compare to Table 1, entry 3, and Table
b
2. By 1H NMR. c 3a and 4a could be separated by HPLC only.
Other material forms as well. e Proceeds slowly. f No reaction at
d
room temperature. Polymerizes at 50 °C.
Ta ble 4. Rea ction of 1a w ith Differ en t P d II Ca ta lysts in
a
Aceton itr ile-d 3
The first route consisted of one step only; but the yields
were low (30-65% depending on the substituent R). The
second, longer route provided excellent yields (usually
more than 80% over two steps). In principle there exist
numerous other ways for the synthesis of R-allenyl
ketones.7,15,27 For our investigation we chose the fastest
access.
ratio of
entry
catalyst
TCPCTFE
Pd(OAc)2
Pd(acac)2
PdCl2(MeCN)2
PdSO4
2a :3a :4a b
1
2
3
4
5
6
7
<1.0:20:traces
1.0:16:2.0
<1.0:20:0
<1.0:20:0
1.0:5.0:traces
<1.0:20:0
<1.0:20:0
PdI2
PdBr2
The substrates 1b-1π were subjected to the TCPCTFE
/
acetone or later to the PdCl2(MeCN)2/MeCN conditions.
The results are summarized in Table 5.17 For some
substrates we applied both conditions in order to secure
that in acetonitrile higher yields of the dimer 3 were
formed in all cases (Table 5, entries 1, 3, 4, and 20).
Selectivity Con cer n in g th e Allen yl Keton e Gr ou p.
The selectivity of the dimerization was remarkable.
a
At 1 M concentration. Compare to Table 1, entry 3, Table 2,
and Table 3. By 1H NMR.
b
2a with decreasing concentration of 1a during the
progress of the reaction was observed.
The other transition-metal catalysts were tested in this
solvent again. However TCPCTFE was still the best
catalyst (Table 3). Triphenylphosphine as additional
ligand inhibited the reaction (Table 3, entry 6).22
3. Th e Aceton itr ile/P d Cl2(MeCN)2-System . Fi-
nally we discovered acetonitrile to be the solvent of choice
for a selective formation of 3 (Table 4, entry 1). Since
the TCPCTFE catalyst is not readily available,23 we looked
for other Pd(II) catalysts (Table 4, entries 2-7).
All of them selectively formed 3 and since it is probably
the easiest available soluble Pd(II)-source, the PdCl2-
(MeCN)2 catalyst24 was used from then on. The effect
was clearly a solvent effect. In other solvents like
benzene, acetone, or CDCl3, several substrates provided
(25) Couffignal, R.; Gaudemar, M. Bull. Soc. Chim. Fr. 1969, 898-
903. Couffignal, R.; Gaudemar, M. Bull. Soc. Chim Fr. 1969, 3218-
3222. Couffignal, R.; Gaudemar, M. Bull. Soc. Chim. Fr. 1970, 3157-
3160. These reactions are always accompanied by a second addition
of 6 to either the intermediate propargyl or allenyl ketone, leading to
tertiary alcohols as side products.
(26) Boeckman, R. J ., J r. In Encyclopedia of Reagents for Organic
Synthesis; Paquette, L. A., Ed; J ohn Wiley & Sons: Chichester, 1995;
vol. 7, pp 4982-4987. Speicher, A.; Bomm, V.; Eicher, T. J . Prakt.
Chem. 1996, 338, 588-590. In the case of allenyl ketones with an
electron-rich substituent R (1s, 1u , 1π) the addition of acetic acid (set
free by the DMP) to the allene was observed as side reaction. The (E)-
configuration of the double-bond in the adduct to 1u , the olefin 28u ,
was proven by X-ray analysis:75
(22) Wallow, T. I.; Novak, B. M. J . Org. Chem. 1994, 59, 5034-
5037. Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L.
S. J . Org. Chem. 1994, 59, 5905-5911. For the formation of oxaphos-
pholes from allenyl ketones and phosphines, see ref 7a and ref 2, p
161.
(23) Only TCPC can be purchased since 1995 (1,2,3,4-tetrakis-
(methoxycarbonyl)-1,3-butadiene-1,4-diyl)palladium).
(24) Hegedus, L. S. In Organometallics in Synthesis; Schlosser, M.,
Ed.; J ohn Wiley & Sons: Chichester, 1994; pp 448-448.
For such additions of carboxylic acids to allenes, see: Smadja, W.
Chem. Rev. 1983, 83, 263-320. Pasto, D. J . Tetrahedron 1984, 40,
2805-2827.
(27) Secondary R-allenic alcohols (or homopropargylic alcohols) are
readily oxidized (or oxidized/isomerized) to allenyl ketones by DMP,
MnO2, chromium oxidants etc., see ref 2.

7298 J . Org. Chem., Vol. 62, No. 21, 1997
Ta ble 5. Resu lts of th e TCP CTF E-Ca ta lyzed Rea ction of 1a -1π
Hashmi et al.
isol yield, %
entry
1
allenyl ketone
cond.a
ratiob 2:3
2
3
1a
R ) CH3
A
B
A
A
B
C
1.0:8.8
1.0:30
-
-
-
3
-
-
86
89
76
67
82
25
(13)
33
(7)
54
76
84
42
83
2
3
1b
1c
R ) (CH2)2CH3
R ) CH(CH2)4
1.0:4.7
1.0:3.0
1.0:3.8
1.0:0.25
:0.12 (4c)
1.0:1.0
:0.2 (4d )
1.0:2.9
1.0:6.0
1.0:3.6
1.0:2.8
1.0:17
4
1d
R ) C(CH3)3
A
-
B
A
A
A
B
11
4
8
-
-
5
6
7
8
1e
1f
1g
1h
R ) CH2C6H5
R ) CH(OTBDMS)CH3
R ) CH(OMOM)CH3
9
1i
B
1.0:14
2
85
10
11
12
13
14
15
16
17
18
19
20
1j
1k
1l
1m
1n
1o
1p
1q
1r
R ) (CH2)3OH
B
A
A
B
B
A
A
A
A
A
A
B
B
A
B
A
A
A
A
B
A
A
A
A
B
B
B
A
A
A
B
B
B
1.0:4.0
1.0:2.2
c
1.0:7.2
1.0:2
c
8
-
-
4
-
6
6
5
4
5
5
-
4
4
5
5
4
-
3
5
-
3
4
5
79
60
21
78
83
74
18
81
81
60
75
81
78
85
72
84
76
90
73
89
72
82
91
45
81
91
86
72
69
75
61
43
37
R ) CH2Cl
R ) CCl3
R ) CH2CH(CH3)(CH2)2CHdC(CH3)3
R ) C(CH2)3CCH2CHdCH2
R ) CHdCHC6H5
R ) CtCC6H5
c
R ) C6H5
1.0:6.1
c
c
1.0:7.2
1.0:32
c
1.0:5.4
c
R ) 4-(OCH3)C6H4
R ) 3,4-(OCH3)2C6H3
R ) 2,5-(OCH3)2C6H3
1s
1t
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
1u
1v
1w
1x
1y
1z
1r
1â
1ø
1δ
1E
1O
1γ
1η
1τ
1θ
1K
1λ
1µ
1ν
1π
R ) 2,4,6-(OCH3)3C6H2
R ) 4-[CH(OCH2CH3)2]C6H4
R ) 4-(CHO)C6H4
R ) 4-(CO2CH3)C6H4
R ) 2-FC6H4
c
1.0:16
1.0:9.0
1.0:8.2
c
1.0:10
c
1.0:11
c
c
R ) 2-ClC6H4
R ) 3-ClC6H4
R ) 4-ClC6H4
R ) 2-BrC6H4
R ) 3-BrC6H4
R ) 2-IC6H4
R ) 3-IC6H4
R ) 1-naphthyl
4
R ) 9-anthryl
c
-
-
-
-
-
-
38
40
R ) 2,4,6-(CH3)3C6H2
R ) 2-furyl
1.0:7.9
1.0:4.1
1.0:5.5
1.0:9.4
1.0:14
1.0:0.5
1.0:0.6
R ) 3-furyl
R ) 2-thienyl
R ) C(CO2CH3)(CH2CtCH)2
R ) 3-(CH(OH)CHdCdCH2)C6H4
R ) 4-(CH(OH)CHdCdCH2)C6H4
a
b
A ) TCPCTFE/acetone; B ) PdCl2(MeCN)2/acetonitrile; C ) TCPCTFE/benzene. By 1H NMR. c Not determined.
Since the conversion readily proceeded at room temper-
ature (some reactions were conducted at 0 °C), no Diels-
Alder reaction between the furyl-group of either product
2 or 3 and the allenyl ketone was observed.28 No [2 + 2]
cycloadducts known from transition-metal-catalyzed
dimerization of unfunctionalized allenes were detected.2,3d
The trisubstituted double bond in 3 was selectively
formed with (E)-configuration and, under the improved
conditions, no isomeric nonconjugated â,γ-unsaturated
ketone 4 was observed.
When this quarternary R-C atom was less sterically
hindered like in the bicyclo[1.1.1]pentane 1n (entry 14),
the percentage of the dimer increased again. R-Siloxy
and R-alkoxy substituents were tolerated well. Here
TBDMS-protected (Table 5, entry 6), MOM-protected
(Table 5, entry 7), ketalic (Table 5, entries 8, 9), and
acetalic (entry 9) substrates were tolerated. The chiral
center R to the ketone in 1h and 1i did not racemize; no
diastereomers were formed. The carbohydrate in entry
9 also shows a benzyl ether protecting group. The
Selectivity Con cer n in g th e Su bstitu en t R. In the
alkyl series with increasing steric bulk of R more of the
monomer 2 was formed (Table 5, entries 1-4). While a
disubstituted R-C atom still gave a reasonable yield of 3
(Table 5, entry 3), a trisubstituted R-C atom led to equal
amounts of 2 and 3 along with some 4 (Table 5, entry 4).
(28) Either
a normal Diels-Alder reaction with the furan as
electron-rich 1,3-diene and the allenyl ketone as electron-poor dieno-
phile or a Diels-Alder reaction with inverse electron-demand, i.e. the
allenyl ketone as 1-oxa-1,3-diene and one double bond of the furan as
dienophile are possible: Bertrand, M.; Le Gras, J . Bull. Soc. Chim.
Fr. 1967, 4336-4343. Gras, J .-L.; Galledou, B. S.; Bertrand, M. Bull.
Soc. Chim. Fr. 1988, 757-767.

Cycloisomerization/Dimerization of Terminal Allenyl Ketones
J . Org. Chem., Vol. 62, No. 21, 1997 7299
protection of the hydroxyl group was not necessary,
entries 10, 40, and 41 show examples with free hydroxyl
groups. This was remarkable, since mercury,29,30 sil-
ver,31,32 and palladium29,33 were also known to catalyze
the nucleophilic addition of such functional groups to
allenes. In entries 11 and 12 R-halogen ketones were
used as substrates (forming benzylic chlorides as prod-
ucts), here Marshall’s silver catalyst would remove the
chlorine. The low yields of isolated product 3l were due
to decomposition of the products during chromatographic
ladium-catalyzed reactions.5d With Marshall’s Ag cata-
lyst a precipitate, probably the silver acetylide, formed
and no catalysis was observed. Secondly, 1µ contained
a 1,6-diyne and an 1,6-enyne subunit (the latter in form
of an 1,6-allenyne). These are known to cyclize to five-
membered carbocycles in palladium-catalyzed reactions,35
and cpCo(CO) causes the formation of six-membered
rings,5g but we did not observe such side reactions. Most
spectacular were the reactions of 1ν and 1π (entries 40
and 41). Here one allene can be addressed specifically
in the presence of a second allenic moiety (both terminal).
To our knowledge this is unique in transition-metal
catalysis. Furthermore the other allenic moiety was an
R-allenic alcohol. These are known to cyclize to dihy-
drofurans when exposed to Hg(II)30 or Ag(I) catalysts.32
In entries 40 and 41 the monomer dominated, which will
be discussed in the mechanistic section.
X-r a y Str u ctu r e An a lyses of th e P r od u cts. With
the two dimers 3t and 3η, X-ray structure determination
was possible.75 Both show the same relative arrange-
ment of the furan and the R,â-unsturated ketone in the
side chain, which is also in accordance with the NOE-
data of 3a , 3h , 3θ, and 3K obtained in solution. The
olefinic hydrogen atom of the trisubstituted double bond
points toward the hydrogen atom at the 3-position of the
furan, and the methyl group points toward the hydrogen
atom at the 5-position. The CdO double bond of the
ketone and the olefin occupy an s-cis-conformation.
1
workupsthe H NMR spectra taken during the reaction
showed a clean conversion. When 3k was purified by
chromatography a yield of 36% was obtained; the yield
given in entry 11 originates from distillation of the crude
product.
Further unsaturation in the molecule was tolerated;
in entries 5 and 9 benzyl groups were present. In entries
13 and 14 a remote olefin and in entry 15 a conjugated
olefin are shown. Conjugated alkynes caused problems,
the yield dropped to 18%, and large amounts of polymer
were formed (entry 16). Placing the triple bond in a more
remote position eliminated these problems (entry 39).
In the aryl series the reaction proceeded well with
hydrocarbon substituents on the aromatic ring (entries
17, 33, 34, and 35). Alkoxy substituents were tolerated
in any position (entry 18-21). Other oxygen-containing
functionalities were a benzylic acetal (entry 22), an
aromatic aldehyde (entry 23), and a carboxylic ester
(entry 24). All halogens were tolerated, independent of
the position on the phenyl substituent (entries 25-32).
With an sp2-carbon R to the ketone steric bulk did not
seem to be a problem. So ortho-substituted (entries 20,
25, 26, 29, and 31) and ortho,ortho-disubstituted phenyl
groups (entries 21, 35) as well as polycyclic aromatic
substrates containing one (entry 33) or two (entry 34)
peri-hydrogens reacted without problem.
Mech a n istic Con sid er a tion s
In the heterocyclic series furyl (entries 36 and 37) and
thienyl substituents (entry 38) gave satisfying results.
Since acetonitrile was used as the solvent in many
cases, it is obvious that the nitrile functionality in the
substrate will be tolerated, too.
Selectivity Con cer n in g F u n ction a l Gr ou p s Th a t
Ar e Kn ow n To Rea ct u n d er Tr a n sition -Meta l Ca -
ta lysis. As far as other possible reactions with transi-
tion-metals are concerned, the aryl halides did not cause
any problems (entries 25-32). In Pd(0)-catalyzed reac-
tions aryl halides are known to react with allenes5e,f and
an activation of acceptor-substituted halides toward
oxidative addition has been reported.34 The substrate 1µ
(entry 39) was remarkable in two aspects. Firstly, it
contains two terminal alkynes. These are known to add
to allenes bearing electron-withdrawing groups in pal-
1. Exp er im en ts Con cer n in g th e Mech a n ism . The
first problem we addressed was the (E)-selectivity in the
formation of the trisubstituted double bond. When the
1
reactions were monitored by H NMR spectroscopy, no
indication for the intermediacy of the (Z)-isomer was
found. In addition, we subjected (E)-9 and (Z)-9 to the
PdCl2(MeCN)2/MeCN conditions. No change was ob-
served. Then 1a was added to the mixture of (E)-9/
PdCl2(MeCN)2 or (Z)-9/PdCl2(MeCN)2. While 2a and 3a
were formed as expected, still no isomerization of (E)-9
or (Z)-9 was observed.
(29) Walkup, R. D.; Guan, L.; Kim, S. W.; Kim, Y. S. Tetrahedron
Lett. 1992, 33, 3969-3972 and literature cited therein.
(30) Gelin, R.; Gelin, S.; Albrand, M. Bull. Soc. Chim. Fr. 1972,
1946-1949.
(31) Chilot, J .-J .; Doutheau, A.; Gore, J . Tetrahedron Lett. 1982, 23,
4693-4696 and literature cited therein.
(32) Gelin, R.; Albrand, M.; Gelin, S. C. R. Acad. Sci. Ser. C 1969,
269, 241-244. Olsson, L.-I.; Claesson, A. Synthesis 1979, 743-745.
Saimoto, H.; Hiyama, T.; Nozaki, H. J . Am. Chem. Soc. 1981, 103,
4975-4977. Nikam, S. S.; Chu, K.-H.; Wang, K. K. J . Org. Chem. 1986,
51, 745-747. Marshall, J . A.; Yu, R. H.; Perkins, J . F. J . Org. Chem.
1995, 60, 5550-5555 and literature cited therein.
(33) (a) Alper, H.; Hartstock, F. W.; Despeyroux, B. J . Chem. Soc.,
Chem. Commun. 1984, 905-906. (b) Walkup, R. D.; Mosher, M. D.
Tetrahedron 1993, 49, 9285-9294. (c) Walkup, R. D.; Guan, L.; Mosher,
M. D.; Kim, S. W.; Kim, Y. S. Synlett 1993, 88-90.
(34) Fitton, P.; Rick, E. A. J . Organomet. Chem. 1971, 28, 287-
291. Bumagin, N. A.; Beletskaya, I. P. Russ. Chem. Rev. 1990, 59,
1174-1184.
Analogous experiments were performed with the double
bond isomers 3d and 4d . No double bond migration took
place.
(35) Trost, B. M. Acc. Chem. Res. 1990, 23, 34-42.

7300 J . Org. Chem., Vol. 62, No. 21, 1997
Hashmi et al.
only and position 4 of 2a . In the case of 3a 13C-NMR
and low-energy ionization mass spectroscopy proved that
only one deuterium was incorporated. This indicated
that the hydrogen migration is intramolecular to a large
extent. Neither in the case of D2O-addition nor in the
case of H2O-addition an increase in the reaction-rate was
observed. These experiments also exclude tautomeriza-
tion of 1 under the reaction conditions. Otherwise one
would expect deuterium also to enrich (due to concentra-
tion and primary kinetic isotope effect) in position 5 of
2a and position 5 and the allylic methyl group of 3a . If
R has a hydrogen atom R to the ketone, this position
should also incorporate deuterium by keto-enol tautom-
erism, which was not observed.
Then deuterium labeled (80% monodeuteration at
position 5) 5-D-1a was cycloisomerized/dimerized. Here
a primary kinetic isotope effect of 3.1 (at 22 °C) was
observed.37 Within experimental error the value was
identical for both products 2a and 3a . This is a necessary
but not sufficient condition for a formation of 2a and 3a
through the same intermediate undergoing the hydrogen
migration.
Two additional crossover experiments between 1a and
1s (one partner monodeuterated, the other undeuterated
in each of the experiments) showed only deuteration at
the expected positions of the statistically formed four
dimers. This is an additional proof for the intramolecu-
larity of the hydrogen-migration. Differing from the
deuterium exchange with the solvent (see above), no
deuterium exchange between the intermediates was
observed due to the low concentration of these intermedi-
ates of the catalytical cycle.13
These experiments proved that the R,â-unsaturated
(E)-olefin 3 was the direct product of the catalytic cycle
and not the product of a subsequent isomerization of a
product mixture ((E/ Z)-3 and/or 4) into a thermodynami-
cally most stable product by either PdCl2(MeCN)2 or any
of the intermediates of the catalytic cycle.
The next experiments dealt with two aspects: The
ability of other related, unsaturated molecules to par-
ticipate in the dimerization reaction and the ability of
these structures to cycloisomerize. In entry 40 and 41
of Table 5, it was already shown that R-allenic alcohols
don’t react with the PdCl2(MeCN)2 catalyst and that they
are not incorporated in the dimerization step (with 1ν
and 1π this would lead to polymerization). Additionally
the two R-allenic alcohols 10 and 11 turned out to be inert
under the TCPCTFE/acetone and the PdCl2(MeCN)2/MeCN
conditions.
In the next experiment we again focused on the
possible participation of tautomers of 1. When 1d is
stirred with D2O/NaHCO3/Et2O almost complete deu-
teration of the vinylic hydrogens was observed, while in
the absence of a base 1d remained unchanged. This
excludes tautomers of 1 as substrates entering the
catalytic cycle.
The last experiment dealt with the oxidation state of
the palladium intermediates. We were able to conduct
the reaction with 1a under 1 atm of pure dioxygen!
2. Th e Na tu r e of th e Ca ta lyst. Since palladium
chloride, bromide, iodide, acetate, acetylacetonate, and
TCPCTFE gave similar results, these ligands on palladium
obviously do not directly participate in the reaction.
Therefore their possible participation, e.g. in the sense
of a halopalladation step (which would be impossible with
TCPCTFE), is omitted in the discussion below.
We will discuss Pd(II)/Pd(IV)-cycles for the following
reasons: One could imagine that Pd(II) is initially
reduced to Pd(0) by the organic substrate,38 and then the
analogous Pd(0)/Pd(II)-cycles could be formulated. But
in the absence of stabilizing ligands one would expect
Pd(0) to precipitate as palladium-black. This was not
observed. Furthermore we were able to conduct the
reaction with 1a under 1 atm of pure dioxygen. This
experiment excludes Pd(0) intermediates in the catalytic
cycle since these are known to react rapidly with oxy-
The alkynyl ketones 12w and 12x (isomers of the
allenyl ketones 1w and 1x) also did neither cyclize nor
were incorporated in the product of the cycloisomeriza-
tion/dimerization of allenyl ketones under our standard
conditions.
These experimental results indicated a higher reactiv-
ity of the allenyl ketones compared to olefins, alkynes,
or other allenes in the cycloisomerization/dimerization
reaction. The high reactivity of the allenic ketones is also
nicely demonstrated by the failure of their isomers 12w
and 12x, respectively, to cycloisomerize under the same
mild conditions.36
The next series of experiments dealt with the nature
of the hydrogen migration. We started with the cycliza-
tion/dimerization of 1a in acetone/D2O, MeCN/D2O (al-
ways a large excess of D2O compared to 1a ), and MeOH-
d4. In all cases only some deuterium was incorporated
(between 40% and 60%) at the allylic methyl group of 3a
(37) Recently similar values have been reported for the â-H-
elimination in Pd(II) complexes, see: Keinan, E.; Kumar, S.; Dangur,
V.; Vaya, J . J . Am. Chem. Soc. 1994, 116, 11151-11152.
(38) Stille, J . K.; Groh, B. L. J . Am. Chem. Soc. 1987, 109, 813-
817.
(39) Maitlis, P. M.; Espinet, P.; Russell, M. J . H., ref 1b, vol. 6, pp
243-263 (specific pp 256-259). Mimoun, H. In The Chemistry of
Functional Groups, Peroxides; Patai, S., Ed; J ohn Wiley & Sons:
London, 1983; pp 463-482. Heumann, A.; J ens, K.-J .; Re´glier, M.
Progr. Inorg. Chem. 1994, 42, 483-576 and literature cited therein.
(36) If one regards the chemoselectivities, the assumption of a higher
reactivity of allenyl ketones is necessary with any mechanism.

Cycloisomerization/Dimerization of Terminal Allenyl Ketones
J . Org. Chem., Vol. 62, No. 21, 1997 7301
gen;39 thus many turnovers of the catalytic cycle should
be impossible with Pd(0). In addition, the aryl halides,
especially the aryl iodides 1E and 1O, should immediately
undergo oxidative addition to a Pd(0) intermediate.40
Then this arylpalladium(II) compounds would carbo-
metalate another allene, thus leading to the kind of
products described by Gore´ and others.41 Furthermore
the addition of nucleophiles to olefins is a domain of
Pd(II) catalysts as exemplified by the Wacker oxidation42
and related reactions.43
If one accepts that Pd(0) is not involved and if one takes
into consideration the intramolecularity of the hydrogen
migration, it becomes necessary to formulate Pd(IV)
intermediates with any mechanism for the formation of
3. Organometallic Pd(IV) complexes are well known in
the literature.44 Even Pd(IV)-hydride species have been
proposed;44a,45 these proposals experience further support
by the recent isolation46 and in one case crystallographic
characterization47 of the related organo-Pt(IV)-hydride
complexes. The solvent dependency of the ratio of 2:3
(see Tables 2 and 4) is also in accordance with the
proposed Pd(IV) intermediates. Since Pd(IV) shows an
octahedral coordination of six ligands, the solvent must
occupy two coordination sites. Good donor ligands (like
MeCN,48 acetone, EtOH, MeOH; nitrogen and oxygen
donor ligands are preferred for Pd(IV)44 and Pt(IV)46) will
stabilize (stabilize does not mean that the compound is
stable, for a catalytic cycle with high turnover frequency
and numbers reactive intermediates are essential) the
Pd(IV) intermediate, thus more of 3 is formed. With
weaker donor ligands (like CDCl3, ethers, and benzene)
the Pd(IV)-H species will form 2 by reductive elimination
before this intermediate can add to a second allene
(pathway A, see below) or the formation of the Pd(IV)-
cycle does not take place that readily (pathway B). The
exclusive formation of the monomer 2 with the Ag(I)
catalyst could be explained by the mechanism proposed
by Marshall,6d where the hydrogen moves by a 1,2-H-
shift rather than by a â-H-elimination (see below), thus
avoiding an unfavorable Ag(III) intermediate but also
preventing C-C-bond formation.
3. P ossible Mech a n ism s. There are two mecha-
nisms (pathways A and B) which are in accordance with
the experimental results. Due to reasons to be discussed
at the end of the description of pathway B we prefer
pathway A. Other existing mechanistic possibilities,
which include steps and intermediates known from other
palladium-catalyzed reactions, but which do not harmo-
nize with our experiments, will be discussed only briefly
(pathways C-E).
P a th w a y A. First the terminal double bond of the
allenyl ketone coordinates to the palladium(II) (this
double bond is less substituted and more electron rich).
The coordination bends the allene,3c,d thus bringing the
terminal carbon within reach of the carbonyl oxygen (at
least in an s-cis conformation, 13). Usually R,â-unsatur-
ated carbonyl compounds with bulky substituents at the
carbonyl group prefer the s-cis conformation necessary
for ring-closure.49 We were able to obtain X-ray struc-
tures from 1r and 1η.50 While 1η shows an s-trans
conformation, 1r occupies an s-cis conformation. The
distance of the oxygen and the terminal carbon of the
allene in 1r is 3.64 Å; coordination to palladium should
bent the allene, and thus the oxygen-carbon distance
discussed above should decrease substantially.51
(40) Mandai, T.; Matsumoto, T.; Tsuji, J . Tetrahedron Lett. 1993,
34, 2513-2516. Hartwig, J . F.; Paul, F. J . Am. Chem. Soc. 1995, 117,
5373-5374.
(41) (a) Hughes, R. P.; Powell, J . J . Organomet. Chem. 1973, 60,
409-425. (b) Ahmar, M.; Barieux, J .-J .; Cazes, B.; Gore, J . Tetrahedron
1987, 43, 513-526. (c) Cazes, B. Pure Appl. Chem. 1990, 62, 1867-
1878.
(42) (a) Eilbracht, P. In Houben Weyl; Helmchen, G., Hoffmann, R.
W., Mulzer, J ., Schaumann, E., Eds.; Thieme: Stuttgart, 1995; vol.
E21c, pp 2702-2712. For Cl- from PdCl2 as nucleophile, see: (b)
Godleski, S. A. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press: Oxford, 1991;
vol. 4, pp 585-661 (specific pp 587-588). (c) Davies, J . A. In
Comprehensive Organometallic Chemistry II; Abel, E. W., Stone, F.
G. A., Wilkinson, G., Puddephatt, R. J ., Eds.; Pergamon Press: Oxford,
1995; vol. 9, pp 291-390 (specific p 330).
(43) Hosokawa, T.; Murahashi, S.-I. Acc. Chem. Res. 1990, 23, 49-
54. For examples with PdCl2(MeCN)2, see: Pearlman, B. A.; Mc-
Namara, J . M.; Hasan, I.; Hatakeyama, S.; Sekizaki, H.; Kishi, Y. J .
Am. Chem. Soc. 1981, 103, 4248-4251. Hosokawa, T. Nakajima, F.;
Iwasa, S.; Murahashi, S.-I. Chem. Lett. 1990, 1387-1390. Kumar, R.
J .; Krupadanam, G. L. D.; Srimannarayana, G. Synthesis 1990, 535-
538. Saito, S.; Hara, T.; Takahashi, N.; Hirai, M.; Moriwake, T. Synlett
1992, 237-238.
(44) Reviews: (a) Canty, A. J . Acc. Chem. Res. 1992, 25, 83-90. (b)
Canty, A. J . Platinum Metals Rev. 1993, 37, 2-7. (c) Canty, A. J ., ref
42c, vol. 9, pp 225-290 (specific pp 272-276). For more recent work,
see: (d) Canty, A. J .; J in, H.; Roberts, A. S.; Skelton, B. W.; White, A.
H. Organometallics 1996, 15, 5713-5722.
(45) Trost, B. M.; Lautens, M. J . Am. Chem. Soc. 1985, 107, 1781-
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1972; Angew. Chem., Int. Ed. Engl. 1996, 35, 1856-1858. Grushin, V.
V. Chem. Rev. 1996, 96, 2011-2033.
Then an oxypalladation of the double bond leads to an
intermediate 14 (Scheme 1).43,52 14 is a γ-donor-
substituted vinylcarbene complex,53,54 but also resembles
a σ-complex of an electrophilic aromatic substitution at
(49) Cherniak, E. A.; Costain, C. C. J . Chem. Phys. 1966, 45, 104-
110. Montaudo, G.; Librando, V.; Caccamese, S.; Maravinga, P. J . Am.
Chem. Soc. 1973, 95, 6365-6370. Bienvenu¨e, A. J . Am. Chem. Soc.
1973, 95, 7345-7353.
(50) So far X-ray structure analyses of only six allenyl ketones are
described in the CCDB; due to geometrical restrictions like rings none
of them provided a reliable value for the C-O-distance.
(51) For the only X-ray structure of a Pd-allene complex, see:
Okamoto, K.; Kai, Y.; Yasuoka, N.; Kasai, N. J . Organomet. Chem.
1974, 65, 427-441. For the only two late transition-metal complexes
of allenyl ketones, see: Suades, J .; Dahan, F.; Mathieu, R. Organo-
metallics 1988, 7, 47-51. Casey, C. P.; Underiner, T. L.; Vosejpka, P.
C.; Gavney, J . A., J r.; Kiprof, P. J . Am. Chem. Soc. 1992, 114, 10826-
10834.
(52) For the participation of carbonyl-oxygen in oxypalladation
steps, see: Imi, K.; Imai, K.; Utimoto, K. Tetrahedron Lett. 1987, 28,
3127-3130.
(46) Ebsworth, E. A. V.; Marganian, V. M.; Reed, F. J . S.; Gould, R.
O. J . Chem. Soc., Dalton Trans. 1978, 1167-1170. Arnold, D. P.;
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Tesauro, D. J . Organomet. Chem. 1995, 488, C13-C14. Hill, G. S.;
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A. J .; Dedieu, A.; J in, H.; Milet, A.; Richmond, M. K. Organometallics
1996, 15, 2845-2847. Holtcamp, M. W.; Labinger, J . A.; Bercaw, J . E.
J . Am. Chem. Soc. 1997, 119, 848-849.
(53) Pd(0): (a) Busacca, C. A.; Swestock, J .; J ohnson, R. E.; Bailey,
T. R.; Musza, L.; Rodger, C. A. J . Org. Chem. 1994, 59, 7553-7556.
(b) Monteiro, N.; Gore´, J ; van Hemelryck, B.; Balme, G. Synlett 1994,
447-449. (c) Farina, V.; Hossain, M. A. Tetrahedron Lett. 1996, 37,
6997-7000. Pd(II): (d) Dixon, K. R.; Dixon, A. C., ref 42c, vol. 9, pp
193-223 (specific pp 216-220). (e) Maitlis, P. M.; Espinet, P.; Russell,
M. J . H. in ref 1b, vol. 6, pp 279-349 (specific pp 292-296). (f) Trost,
B. M.; Hashmi, A. S. K. Angew. Chem. 1993, 105, 1130-1132; Angew.
Chem., Int. Ed. Engl. 1993, 32, 1085-1087. (g) Trost, B. M.; Hashmi,
A. S. K. J . Am. Chem. Soc. 1994, 116, 2183-2184. See also ref 54. For
stable bis-carbene complexes of Pd(II), see: (h) Herrmann, W. A.;
Elison, M.; Fischer, J .; Ko¨cher, C.; Artus, G. R. J . Angew. Chem. 1995,
107, 2602-2605; Angew. Chem., Int. Ed. Engl. 1995, 34, 2371-2374.
(i) Enders, D.; Gielen, H.; Raabe, G.; Runsink, J .; Teles, J . H. Chem.
Ber. 1996, 129, 1483-1488.
(47) O’Reilly, S. A.; White, P. S.; Templeton, J . L. J . Am. Chem. Soc.
1996, 118, 5684-5689.
(48) MeCN is considered to be a good σ-donor and a weak π-acceptor,
but still to be labile enough to be substituted by the substrate: Storhoff,
B. N.; Lewis, H. C., J r. Coord. Chem. Rev. 1977, 23, 1-29. Endres, H.
In Comprehensive Coordination Chemistry; Wilkinson, G., Gillard, R.
D., McCleverty, J . A., Eds.; Pergamon Press: Oxford, 1987; vol. 2, pp
261-267.
(54) (a) Wada, M.; Koyama, Y. J . Organomet. Chem. 1980, 201, 477-
491. (b) Wada, M.; Koyama, Y.; Sameshima, K. J . Organomet. Chem.
1981, 209, 115-121.

7302 J . Org. Chem., Vol. 62, No. 21, 1997
Hashmi et al.
Sch em e 1
the furan.55 The protonated furan is acidic,54b and the
d-electron-pair at Pd is an internal base.56 â-H-elimina-
tion would form the aromatic furan in the furyl-hydrido
complex 16.6d Such â-H-eliminations of carbene com-
plexes have been proposed.53a,57,58 The fact that in protic
deuterated solvents 40-60% of the hydrogen remains in
the product is also a proof for the intramolecularity of
the major part of the H-migration (C-H to Pd-H to
C-H). Due to a certain acidic character of the interme-
diate Pd(IV)-H species some of the hydrogen is exchanged
by the deuterium of the solvent; the H/D exchange may
to some extent also result from nonintramolecular H-
migration.
described above (â-H-elmination followed by reductive
elimination).61 The direct 1,2-H-shift would not allow the
formation of the dimer 3 by the same pathway.
16 also could carbopalladate the terminal double bond
of a second allenyl ketone (to 17).41,62 The selectivity for
this more electon rich double bond may be explained by
the electron deficiency of the Pd(IV) intermediate. The
palladium also preferentially coordinates to the less
hindered face of this double bond, which is anti to the
carbonyl-substituent. This would explain the (E)-selec-
tivity in the formation of the trisubstituted double bond.
The regiochemistry of the carbopalladation can be ex-
plained by steric (the palladium complex ends up on the
less substituted carbon) and electronic factors (the nu-
cleophilic furyl carbon gets attached to the more electro-
philic central carbon of the allene). Carbopalladations
of allenes are known to favor C-C bond formation at the
central carbon of the allene.5a,b,d,i,33a,c,41b,63 In the case of
a hydropalladation, instead of a carbopalladation, the
hydrogen should end up at the central carbon of the
allene,5h,i which neither we observed nor has been
Now 16 can form 2 by reductive elimination. The
formation of olefins by a 1,2-shift from carbene complexes
is well known in the literature59 and might proceed
directly (1,2-H-shift forming the π-coordinated olefin
complex without change in the oxidation state of the
metal, probably true for the Ag(I)-catalysts)60 or as
(55) The protonation of furans occurs in 2-position: Unverferth, K.;
Schwetlick, K. J . Prakt. Chem. 1970, 312, 882-886. Salomaa, P.;
Kankaanpera¨, A.; Nikander, E.; Kaipainen, K.; Aaltonen, R. Acta
Chem. Scand. 1973, 27, 153-163.
(56) For the agostic interaction of hydrogen in a Pd(II) complex,
see: Roe, D. M.; Bailey, P. M.; Moseley, K.; Maitlis, P. M. J . Chem.
Soc., Chem. Commun. 1972, 1273-1274. Compare also Ryabov, A. D.
Chem. Rev. 1990, 90, 403-424.
(57) The (partially) reverse reaction, the formation of a carbene
complex by the protonation of a vinyl complex has been described for
Pd (ref 54a) and Ni, see: Wada, M.; Sameshima, K.; Nishiwaki, K.;
Kawasaki, Y. J . Chem. Soc., Dalton Trans. 1982, 793-797.
(58) (a) Fournier-Nguefack, C.; Lhoste, P.; Sinou, D. Synlett 1996,
553-554. (b) Yamamoto, A. J . Organomet. Chem. 1995, 500, 337-348.
For â-H-eliminations in η3-allylpalladium(II) complexes, see ref 37.
With Ni(II)-compounds, see: (c) Pasynkiewicz, S. J . Organomet. Chem.
1995, 500, 283-288.
(59) Mu¨ller, P.; Pautex, N.; Doyle, M. P.; Bagheri, V. Helv. Chim.
Acta 1990, 73, 1233-1241. Taber, D. F.; Hennessy, M. J .; Louey, J . P.
J . Org. Chem. 1992, 57, 436-441 and literature cited therein.
Compare: Taber, D. F. In Houben Weyl; Helmchen, G., Hoffmann, R.
W., Mulzer, J ., Schaumann, E., Eds.; Thieme: Stuttgart, 1995; vol.
E21a, pp 1127-1148 (specific p 1145).
(60) Shirafuji, T.; Yamamoto, Y.; Nozaki, H. Tetrahedron Lett. 1971,
4713-4714. Leftin, J . H.; Gil-Av, E. Tetrahedron Lett. 1972, 3367-
3370.
(61) Such â-H-eliminations usually follow the oxypalladation of
olefins, see ref 43.
(62) Yamamoto, Y.; Al-Masum, M.; Asao, N. J . Am. Chem. Soc. 1994,
116, 6019-6020. Carbopalladation of a acceptorsubstituted alkene by
a Pd(II)-H species was suggested by Trost, B. M.; Toste, F. D. J . Am.
Chem. Soc. 1996, 118, 6305-6306.

Cycloisomerization/Dimerization of Terminal Allenyl Ketones
J . Org. Chem., Vol. 62, No. 21, 1997 7303
observed in reactions where alkynylPdH5d or other PdH
intermediates5i,62 add to allenes.
Sch em e 2
In entry 40 and 41 of Table 5 the monomer is formed
preferentially. This can be interpreted by a blocking of
the coordination site for the second allenyl ketone by the
R-allenic alcohol. Here the relative rates of reductive
elimination versus carbopalladation favors the furans 2.
This can be explained by the allenyl ketones being
extremely effective trapping reagents for such intermedi-
ates, but unfortunately also cyclize under these condi-
tions and thus trap themselves.
No polymers are formed, since arylPdH species (16)
are more stable than alkylPdH species (17) (for the higher
stability of arylPd versus alkylPd in the formal oxidation
state Pd(IV)44), the latter reductively eliminates R-H
much faster.
Finally the product 3 is formed by a fast subsequent
reductive elimination from the σ-allyl complex 17. Rear-
rangement to an π-allyl complex 18 and reductive
elimination could explain the byproduct 4.
This pathway resembles the formation of furans by
FVT of allenyl ketones (see Introduction). Huntsman
recognized that one hydrogen must migrate to the central
carbon of the allene, no matter whether first cyclization
and then migration or first migration and then cyclization
occurs, and that it was necessary to discuss carbene
intermediates. The metal catalyst now stabilizes these
high energy intermediates (by forming carbene com-
plexes), thus opening a pathway with a lower energy of
activation. The metal also prolongs the lifetime of the
intermediates, so the additional C-C-coupling is possible.
P a th w a y B. The reaction is initiated by the formation
of the palladacyclopentane 23 (Scheme 2).5c,64 Here the
first step forms the C-C bond between the central carbon
atoms of the two allenes. Several isomers of 23 are
conceivable, which maybe interconvert by allyl-shifts of
the metal.65 Nucleophilic attack of oxygen to the neigh-
boring exocyclic double bond forms the intermediate 24.
A 1,2-shift of the metal eliminates the positive charge
on the oxygen and leads to the 3-methylenepalladacy-
clobutene 15 or a trimethylenemethane-like intermediate
25.66 Now â-H-elimination forms the furan 17, and the
reaction is finished as described above. Here we are not
certain how the specific formation of the (E)-olefin in the
product 3 can be explained.
2a and 3a through the intermediates and thus a weak
argument against pathway B (since this pathway leads
to 3 only). Still, the palladium would eliminate the
hydrogen or the deuterium from the syn-face, and none
of the complexes 15a and 15b (or 25a and 25b) should
be preferred either sterically or electronically. Thus in
pathway B a primary kinetic isotope effect could be only
explained if the Pd changes the faces faster than the
â-hydrogen elimination occurs.
The identical primary kinetic isotope effects of 3.1 (at
22 °C) observed in the formation of 2a and 3a 37 is a
necessary but not sufficient condition for a formation of
(63) Shimizu, I.; Tsuji, J . Chem. Lett. 1984, 233-236. Larock, R.
C.; Varaprath, S.; Lau, H. H.; Fellows, C. A. J . Am. Chem. Soc. 1984,
106, 5274-5284. Larock, R. C.; Berrios-Pena, N. G.; Fried, C. A. J .
Org. Chem. 1991, 56, 2615-2617. Davies, I. W.; Scopes, D. I. C.;
Gallagher, T. Synlett 1993, 85-87.
(64) Pasto, D. J .; Huang, N.-Z.; Eigenbrot, C. W. J . Am. Chem. Soc.
1985, 107, 3160-3172. Hegedus, L. S.; Kambe, N.; Ishii, Y.; Mori, A.
J . Org. Chem. 1985, 50, 2240-2243. Stephan, C.; Munz, C.; tom Dieck,
H. J . Organomet. Chem. 1994, 468, 273-278. Hughes, R. P.; Powell,
J . J . Organomet. Chem. 1969, 20, P17-P19. Broadbent, T. A.; Pringle,
G. E. J . Inorg. Nucl. Chem. 1971, 33, 2009-2014. For related
palladacycles in the formal oxidation state (IV), see ref 35 and
Blomquist, A. T.; Maitlis, P. M. J . Am. Chem. Soc. 1962, 84, 2329-
2334.
(65) J olly, P. W. Angew. Chem. 1985, 97, 279-291; Angew. Chem.,
Int. Ed. Engl. 1985, 24, 283-295.
More evidence against pathway B is provided by the
cyclization of 1µ (Table 5, entry 39). If a palladacycle is
formed, it would be difficult to understand why in the
case of 1µ an intramolecular incorporation of the alkyne
to the intermediate 26 is not preferred. Then 27 would
form, but we could not detect 27 or products derived from
27.
(66) Lautens, M.; Ren, Y. J . Am. Chem. Soc. 1996, 118, 9597-9605;
for a X-ray structure analysis of a related structure, see: Su, C.-C.;
Chen, J .-T.; Lee, G.-H., Wang, Y. J . Am. Chem. Soc. 1994, 116, 4999-
5000.
(67) The formation of palladacyclobutane from palladium(II) car-
benoids and olefins has been proposed, see: Taber, D. F.; Amedio, J .
C., J r.; Sherrill, R. G. J . Org. Chem. 1986, 51, 3382-3384. Hoye, T.
R.; Dinsmore, C. J .; J ohnson, D. S.; Korkowski, P. F. J . Org. Chem.
1990, 55, 4518-4520.

7304 J . Org. Chem., Vol. 62, No. 21, 1997
Hashmi et al.
Traces of water might always be present, and if the
rate-determining step is not the formation of the hydrate,
one would not expect a rate enhancement by additional
water. However the reaction of 1τ (Table 5, entry 35)
provides a strong evidence against pathway E. One
would at least expect a much slower reaction, since the
formation of the tetrahedral sp3-center in the ketone
hydrate from the trigonal sp2-center in the ketone is
usually avoided due to steric hinderance in the mesityl
system.72 But the cycloisomerization/dimerization of 1τ
was finished within the normal time.
P a th w a y C. In this pathway only the transformation
of 14 to 17 differs from pathway A. Here the C-C bond
is not formed by carbopalladation but by a [2 + 2]
cycloaddition of the carbene complex and the less hin-
dered face of the terminal double bond of the allene
(intermediate 15; for other possible forms of 15 see
pathway B).67,68 Subsequent â-H-elimination leads to 17,
and then the reaction proceeds similar to pathway A. This
means that the formation of the monomer 2 and the
dimer 3 branch before the â-H-elimination. As in path-
way B there should not exist any preference for either of
the two [2 + 2] cycloadducts 15a and 15b (respectively,
25a and 25b). Therefore no primary kinetic isotope effect
would be possible.
P a th w a y D. Here 16 is formed by an alternative
mechanism. 1 might exist in an equilibrium with its
tautomer 19. With a (Z)-configuration at the double bond
such 1-buten-3-yn-1-ol substructures are known to cyclize
to furans in palladium-catalyzed reactions. When 2-hy-
droxy-haloarenes and terminal alkynes are cross-coupled
in the presence of palladium catalysts, the 2-alkynylphe-
nols cannot be isolated. The reactions proceed to the
isomeric benzofurans,69 unless the hydroxyl group is
protected.70 In the case of the tert-butyl and aryl sub-
stituents 19 would be the only possible tautomer of 1.
Other substituents which possess an R-hydrogen could
also form an enol in the other direction, but our experi-
ments exclude the participation of such tautomers.
P a th w a y E. This is another alternative for the
formation of 16. First a hydrate 21 is formed, and then
an oxypalladation of the terminal double bond leads to
intermediate 22. Similar steps are known from the
formation of 2,5-dihydrofurans from R-allenic alcohols30,32
and have also been suggested by Utimoto for the cycliza-
tion of â-acetylenic ketones by Pd catalysts71 and by
Walkup for the Pd-catalyzed cyclization of γ-allenic
alcohols.33b
The intermediate 22 (which could also be formed by
the addition of H2O to 14) then forms the aromatic furan
system 16 by loss of water. One proton of the methylene
group in the heterocycle may be transferred to the
palladium by a â-H-elimination or leave to the solvent.
Finally 16 carbopalladates a second molecule 1 as
described above. This carbopalladation may also take
place before the elimination of water.
Con clu sion s a n d F u r th er Stu d ies
By the choice of PdCl2(MeCN)2 catalyst and acetonitrile
solvent, the dimers 3 could be obtained in preparatively
useful yields under mild conditions. Only traces of the
monomer 2 were observed, and the isomer 4 was not
detected. Neither water nor oxygen needs to be excluded
for a successful catalysis. Many functionalities and
protecting groups that are frequently used in organic
synthesis were tolerated. Among them are functional
groups such as aryl bromides, terminal alkynes, 1,6-
enynes, and R-allenic alcohols that are all known to react
in palladium-catalyzed reactions; therefore, tandem se-
quences seem possible. R-Halogen ketones and terminal
alkynes that cannot be isomerized with Marshall’s silver
catalysts also reacted well. On the basis of several
control experiments and the observed intriguing selec-
tivities, we favor pathway A for the mechanism of the
reaction although pathway B could not be excluded. Only
a complete understanding of the mechanism might
enable us to transfer this exciting selectivity to other
reactions.
Intramolecular macrocyclization of 1,n-diallenyl dike-
tones is another interesting field that is currently under
investigation. The formation of 3, which contains an
dendralenic73 double bond arrangement, also opens an
easy route to substrates for diene-transmissive Diels-
Alder reactions.74
Ack n ow led gm en t. A.S.K.H. is grateful to the Fonds
der Chemischen Industrie for a J ustus von Liebig
fellowship and to Prof. Dr. J . Mulzer for his generous
support. This work was further supported by the Deut-
sche Forschungsgemeinschaft (Ha 1932/3-1 and Ha
1932/3-2). Some noble metal salts were donated by the
Degussa AG. We thank S. Guffler for a generous gift of
1n .
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for 1-5, 8-12, 28, and intermediates 29-37 and methods
of preparation (50 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
J O970837L
(68) For a recent review on metallacyclobutanes, see: J ennings, P.
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o-alkynylphenols as substrates: Kundu, N. G.; Pal, M.; Mahanty, J .
S.; Dasgupta, S. K. J . Chem. Soc., Chem. Commun. 1992, 41-42. Torii,
S.; Xu, L. H.; Okumoto, H. Synlett 1992, 515-516. Candiani, I.;
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5596-5608 and literature cited therein.
(75) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.