The first Heck reactions with 1-chloroalk-1-ynes: Syntheses of enynes with isolated and conjugated π-systems

Article abstract of DOI:10.1007/PL00010146

The Heck reaction between 1-chloro-2-phenylacetylene and cycloalkenes or cycloalkadienes affords phenylethynyl substituted cycloalkenes as regular Heck products as well as 1,3-diphenylprop-2-ynylidene and (cycloalkenyl)phenylmethylidene substituted bicyclic compounds as tandem products by reaction of ClC≡CPh and the cycloalkene in a ratio of 1:2 and 2:1, respectively.

Full text of DOI:10.1007/PL00010146

Monatshefte f uÈ r Chemie 129, 1329±1334 (1998)
Short Communication
The First Heck Reactions with 1-Chloroalk-
1-ynes: Syntheses of Enynes with Isolated
and Conjugated p-Systems
1
1
1
1
Michael Weigelt , Diana Becher , Dieter Str oÈ hl , Clemens Bruhn ,
2
1;Ã
Eike Poetsch , and Dirk Steinborn
1
Institut f uÈ r Anorganische Chemie der Martin-Luther-Universit aÈ t Halle-Wittenberg, D-06099 Halle,
Germany
2
Merck KGaA, D-64271 Darmstadt, Germany
Summary. The Heck reaction between 1-chloro-2-phenylacetylene and cycloalkenes or cycloalk-
adienes affords phenylethynyl substituted cycloalkenes as regular Heck products as well as 1,3-
diphenylprop-2-ynylidene and (cycloalkenyl)phenylmethylidene substituted bicyclic compounds as
tandem products by reaction of ClC:CPh and the cycloalkene in a ratio of 1:2 and 2:1, respectively.
Keywords. Heck reaction; 1-Chloroalk-1-ynes; Cycloalkenes; Cycloalkadienes; Enynes.
Die ersten Heck-Reaktionen mit 1-Chloralk-1-inen: Synthesen von Eninen mit isolierten
und konjugierten p-Systemen (Kurze Mitt.)
Zusammenfassung. Die Heck-Reaktion zwischen 1-Chlor-2-phenylacetylen und Cycloalkenen oder
Cycloalkadienen ergibt phenylethinylsubstituierte Cycloalkene als normale Heck-Produkte sowie
1,3-diphenylprop-2-inyliden- und (cycloalkenyl)phenylmethyliden-substituierte Bicyclen als Tan-
demprodukte der Reaktion von ClC:CPh und Cycloalkenen im Molverh aÈ ltnis von 1:2 bzw. 2:1.
Introduction
The palladium catalyzed vinylation of organic halides RX (Heck reaction) both
with conventional catalyst systems (e.g. Pd(OAc) /P(o-tol) /NEt ) and under
2
3
3
hydroorganylation conditions with Larock catalyst systems [1] (e.g. Pd(OAc)2/
NEt Bz)Cl/NaO CH) is one of the most important C±C bond formation reactions
(
3
2
in synthetic organic chemistry. As RX, mainly aryl, heterocyclic, vinyl, and benzyl
iodides are used [2].
It has been reported that BrC:CPh does not afford Heck products but 1,4-
diphenylbutadiine as homodimer [3]. IC:CR reacts with vinylogous carbonyl
à Corresponding author

1330
M. Weigelt et al.
0
0
compounds to give enynoates and enynones RC:C±CH=CH±C(O)R (R ˆOMe,
Me) [4]. Apart from this, 1-halolalk-1-ynes have not been used successfully in
Heck reactions [5]. Here we report the reaction of 1-chloroalk-1-ynes with
cycloalkenes and cycloalkadienes employing Larock catalyst systems.
Results and Discussion
Reactions of XC:CPh (X ˆ I, Br, Cl) [6] with cyclohexene in the presence of a
typical Larock catalyst system (Pd(OAc) /(NEt Bz)Cl/NaO CH ˆ 1:20:60 in
2
3
2
DMF; 5 mol% Pd referred to XC:CPh) show that the yield of Heck products is
highest using the chloroalkyne, whereas the iodoalkyne does not react to Heck
products at all (Table 1). In all three cases, the haloalkynes react to give oligomers
as the main products. In the case of BrC:CPh, oligomers up to a polymerization
degree of 16 were identi®ed by means of MALDI-MS measurements. As blank
experiments prove (Table 1), these oligomerization reactions are not even in part
palladium catalyzed. The formation of 1,4-diphenylbutadiyne is only a minor side
reaction and was not observed when using the chloroalkyne.
In general, the reactions of cycloalkenes with 1-chloro-2-phenylacetylene in
the presence of the above mentioned catalyst system proceed to give the regular
Heck products (reaction of 1 mol of cycloalkene with 1 mol of ClC:CPh; 1:1
product). Furthermore, tandem reactions occur yielding 1,3-diphenylprop-2-
ynylidene and (cycloalkenyl)phenylmethylidene substituted bicyclic compounds
by reaction of 1 mol cycloalkene with 2 mol ClC:CPh (1:2 product) and 2 mol
cycloalkene with 1 mol ClC:CPh (2:1 product), respectively (Scheme 1, Table 2).
Table 1. Heck reaction of XC:CPh with cyclohexene and stability of XC:CPh in DMF
X
Heck reaction (with Pd cat.)
Decomp. reaction (without Pd cat.)
a
b
b
c
b
U (%)
n(Heck prod.)
n(Ph C )
2
U(%)
n(Ph C )
2 4
4
1
2
3
I
100
100
86
<1
12
24
1
3
0
89
51
15
6
3
0
Br
Cl
a
Degree of conversion of XC:CPh in the Heck reaction (catalyst system: see text) with cyclohexene
ꢀ
b
c
(
c(cyclohexene):c(XC:CPh) ˆ 15:1, 48 h, T ˆ 25 C; mol%; degree of conversion of XC:CPh
ꢀ
yielding oligomers in DMF (t ˆ 48 h, T ˆ 25 C)
Scheme 1

Heck Reactions with 1-Chloroalk-1-ynes
1331
Table 2. Product distribution in the Heck reaction of cycloalkenes and cycloalkadienes with ClC:CPh
ꢀ
(
catalyst system: see text; T ˆ 25 C)
a
b
Ole®n
col : cClCꢁCPh
t (d) Ugc (%)
Product distribution (%)
1
:1
1:2
2:1
0:2
c
1
2
3
4
5
6
7
8
9
cyclohexene
15:1
15:1
1:1
2
4
4
4
4
4
4
2
1
24
69
33
53
84
44
72
34
24
10
24
14
56
90
86
93
85
27
75
8
7
60
14
38
±
±
±
±
±
6
1
3
±
2
cycloheptene
cycloheptene
66
±
cis-cyclooctene
50:1
50:1
30:1
50:1
15:1
15:1
1,4-cyclohexadiene
1,3-cycloheptadiene
cis,cis-1,5-cyclooctadiene
±
4
7
3
±
d
4-vinylcyclohexene
±
±
p-methylstyrene
±
67
a
b
Degree of conversion of ClC:CPh to low-molecular products; differences to 100% arise from
unidenti®ed products; the main isomer is 4-(phenylethynyl)cyclohexene; analogously, 4-substituted
c
d
cyclohexenes were found to be the main products in the Heck arylation of cyclohexene [9]; catalyst
ꢀ
system: Pd(OAc) /P(o-tol) /NaOAc ˆ 1:2:60, solvent: DMF, T ˆ 100 C
2
3
Due to hydroorganylation conditions, hydrogenation of triple and/or double bonds
was also observed.
In the reaction with cyclohexene, the 1:2 product is the major one (Table 2,
entry 1), whereas in the reaction with cycloheptene the ratio of products can be
in¯uenced by the ratio of cycloheptene to ClC:CPh (entries 2 and 3). With cis-
cyclooctene, normal Heck reaction predominates (entry 4). Cycloalkadienes were
found to react affording phenylethynylcycloalkenes as the principal products
(entries 5±7), i.e., regular Heck reactions under hydrogenation of one double bond
take place. The homodimer 1,4-diphenylbutadiyne (0:2 product) is formed to a
small extent only. The reaction of ClC:CPh with p-methyl-styrene (included in
Table 2, entry 9, for comparison) affords the 2:1 compound as the main product.
A plausible route for the formation of the tandem products is outlined in
Scheme 2. The formation of the 1:1 products via A and B as intermediates is
depicted in the ®rst line. Intermediate B may also undergo an intramolecular
insertion reaction to give C which in turn reacts either with cycloalkenes yielding
the 2:1 products or with A in the sense of a transmetallation and reductive
elimination affording the 1:2 products. The transmetallation may have a four-
centered transition state [7]. A Pd(IV) intermediate formed by oxidative addition of
ClC:CPh to C followed by a reductive elimination may also be discussed [8]. The
formation of the 1:2 products via a Heck reaction of the 1:1 products with D as an
intermediate and a subsequent intramolecular insertion reaction was rendered
unlikely by a separate experiment (4-(phenylethynyl)cyclohexene (Table 3, entry
5
) and ClC:CPh do not react to the corresponding Heck products).
The major products were obtained with yields between 14 and 73% (GC) and
6
completely characterized by one- and two-dimensional H and C NMR
±49% (isolated, not optimized), respectively (Table 3). All substances were
1
13

1332
M. Weigelt et al.
Scheme 2
Table 3. Syntheses of enynes with isolated and conjugated ꢀ-systems (reaction conditions as in
Table 2)
Ole®n
Product type
Yield (%) gc/isol
purity (%))
(
1
2
3
cyclohexene
cycloheptene
cycloheptene
1:2
2:1
1:2
7-(1,3-diphenylprop-2-ynylidene)-
bicyclo[2.2.1]heptane
18/13 (> 97)
8-((cyclohept-4- and 8-((cyclohept-3-enyl)- 41/11 (> 97)
phenylmethylidene)bicyclo[3.2.1]octane
8-(1,3-diphenylprop-2-ynylidene)-
bicyclo[3.2.1]octane
17/8 (> 99)
4
5
6
7
cis-cyclooctene
1:1
1:1
4- and 5-(phenylethynyl)cyclooctene
a
4-(phenylethynyl)cyclohexene
24/18 (> 90)
73/36 (> 98)
14/11 (> 81)
61/49 (> 97)
1,4-cyclohexadiene
1,3-cycloheptadiene 1:1
cis,cis-1,5-cycloocta- 1:1
diene
4-(phenylethynyl)cycloheptene
5-(phenylethynyl)cyclooctene
8
4-vinylcyclohexene
1:1
4-(1-(phenylethynyl)vinyl)cyclohexene
20/6 (> 92)
a
In dry DMF; in wet DMF, the hydrogenated products (Z)-4-(2-phenylethenyl)cyclohexene or 4-(2-
phenylethyl)cyclohexene were obtained
experiments. The molecular structure of the bicyclic enyne (Table 3, entry 1) was
also authenticated by X-ray diffraction analysis (Fig. 1).
It was shown for the ®rst time that 1-chloro-2-phenylacetylene is a useful
starting material for Heck reactions with cycloole®ns and cyclodienes yielding not
only the regular Heck products but also bicylic unsaturated hydrocarbons. In

Heck Reactions with 1-Chloroalk-1-ynes
1333
Fig. 1. Molecular structure of 7-(1,3-diphenylprop-2-ynylidene)bicyclo[2.2.1]heptane
further investigations it was demonstrated that other 1-chloroalk-1-ynes (ClC:CR,
R ˆ n-butyl, n-octyl, cyclohexyl) react analogously.
Experimental
Typical procedure
The ole®n (15.0 mmol), 1-chloro-2-phenylacetylene (136 mg, 1.0 mmol), and the catalyst (Pd(OAc)2,
1
1 mg, 0.05 mmol; (NEt Bz)Cl, 228 mg, 1.0 mmol; NaO CH, 204 mg, 3.0 mmol) were stirred in
3 2
ꢀ
DMF (2 ml) under argon in the dark at 25 C for 2±4 d. After addition of water (20 ml) the precipitate
was ®ltered and washed with ether. From the combined organic phase (dried over Na SO ), the
2
4
solvents were removed in vacuo. The residue was analyzed by gas chromatography using biphenyl as
internal standard.
For preparative purposes the reactions were performed as described above but on a ®vefold scale.
The residue obtained after removal of solvents was puri®ed by means of preparative centrifugally
accelerated thin-layer chromatography (Chromatotron, Harrison Research) on silica gel using
n-hexane as eluent (1±3 runs).
7-(1,3-diphenylprop-2-ynylidene)bicyclo[2.2.1]heptane (as a representative)
ꢀ
1
Colorless crystals; m.p.: 80±81 C; H NMR (500 MHz, CDCl ): ꢁ ˆ 1.41±1.59 (m, 4H, H2endo,
3
H3endo, H5endo, H6endo), 1.68±1.82 (m, 2H, H3exo, H5exo), 1.82±1.94 (m, 2H, H2exo, H6exo), 2.83 (t,
3
3
1
H, J ˆ 4.2 Hz, H4), 3.03 (t, 1H, J
ˆ 4.4 Hz, H1), 7.24±7.34 (m, 4H, H of 1-Ph, 3-Ph,
H,H
H,H
p
2
ÂHo of 3-Ph), 7.34±7.40 (m, 2H, 2ÂHo of 1-Ph), 7.44±7.52 (m, 4H, 2ÂHm of 1-Ph and 3-Ph) ppm;
1
3
C NMR (100 MHz, CDCl ): bicyclo[2.2.1]heptane: ꢁ ˆ 28.30 (C2 ‡ C6), 29.02 (C3 ‡ C5), 37.00
3
1
1
(
C4,
J
ˆ 146.6 Hz), 40.05 (Cl,
J
ˆ 145.6 Hz), 161.29 (C7) ppm; 1,3-diphenylprop-2-
C,H
C,H
3
ynylidene: ꢁ ˆ 88.55 (C3, J , ˆ 5.0 Hz), 89.54 (C2), 108.55 (C1), 124.03 (Ci of 3-Ph,
C H
i
m
3
JC ;H ˆ 8:0 Hz), 126.81/127.63 (Cp of 1-Ph and 3-Ph), 128.02 (2ÂCo of 1-Ph), 128.17 (2ÂCo of
i
m
3
-Ph), 128.47/131.40 (Cm of 1-Ph and 3-Ph), 139.07 (Ci of 1-Ph, 3JC ;H ˆ 8:0 Hz) ppm; the
i
m
‡
numbering follows Fig. 1; MS (70 eV): m/z (%) ˆ 285 (22) [M‡1], 284 (100) [M ], 283 (22)
�
Ê Ê Ê
1
[
M� 1]; IR (KBr): ꢂ(C:C) ˆ 2202 cm ; X-ray structure analysis (STOE IPDS): space group: P2 /a;
1
ꢀ
unit cell parameters: a ˆ 17.427(3) A, b ˆ 10.015(3) A, c ˆ 19.293(4) A, ꢃ ˆ 100.44(2) , Z ˆ 8;
ꢀ
ꢄ-range: ꢄ ˆ 2.30±23.99 ; re¯. (coll.): 22591; data/parameters: 5179/397; ®nal R indices:
R ˆ 0.0672 (I >2ꢅ(I)], wR ˆ 0.1829 (all data).
1
2

1334
M. Weigelt et al.: Heck Reactions with 1-Chloroalk-1-ynes
Acknowledgements
Financial support from the Deutsche Forschungsgemeinschaft is acknowledged. We are grateful to
Dr. R. Kr uÈ ger (Bundesanstalt f uÈ r Materialpr uÈ fung, Berlin) for MALDI-MS measurements.
References
[
1] Larock RC, Johnson PL (1989) J Chem Soc Chem Commun 1368
2] Heck RF (1991) In: Trost BM, Fleming J (eds) Comprehensive Organic Synthesis, vol 4.
Pergamon, Oxford, p 833; Cabri W, Candini I (1995) Acc Chem Res 28: 2; De Meijere A,
Meyer FE (1994) Angew Chem 106: 2473
[
[
[
[
3] Dieck HA, Heck PF (unpublished results) cited in: Heck RF (1982) Org React 27: 345
4] Jefferey T (1987) Synthesis 70
5] For the use of haloalkynes in cross-coupling reactions see: Sonogashira K (1998) In: Diederich F,
Stang PJ (eds) Metal-Catalyzed Cross-Coupling Reactions. Wiley-VCH, Weinheim, p 203
6] ClC:CPh: Makosza M, Fedorynski M (1975) Rocz Chem 49: 1779; BrC:CPh: H aÈ nninen E,
Takalo H, Kankare J (1988) Acta Chem Scan 42B: 614; IC:CPh: Lee GCM, Tobias B, Holmes
JM, Harcout DA, Garst ME (1990) J Am Chem Soc 112: 9330
[
[
[
[
7] Matos K, Soderquist JA (1998) J Org Chem 63: 461
8] Canty AJ (1992) Acc Chem Res 25: 83
9] Steinborn D, Lorenz P, Lechler J-U, Poetsch E (1995) DE 195 06 442 A1 v. 24. 2. 1995
Received September 7, 1998. Accepted September 14, 1998