Iridium(I)-catalyzed cycloisomerization of cyclohexadienyl alkynes

Article abstract of DOI:10.1002/adsc.200900578

From cyclohexadienyl alkynes with a terminal alkyne unit, double cyclopropanated products were obtained in reasonable to high yields. For cyclohexadienyl alkynes substituted at the alkyne unit, cyclopropanated products were obtained in high yields. When a

Full text of DOI:10.1002/adsc.200900578

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DOI: 10.1002/adsc.200900578
Iridium(I)-Catalyzed Cycloisomerization of Cyclohexadienyl
Alkynes
So Hee Sim,a Sang Ick Lee,a Ji Hoon Park,a and Young Keun Chunga,*
a
Intelligent Textile System Research Center, and Department of Chemistry, College of Natural Sciences, Seoul National
University, Seoul 151-474, Korea
Fax : (+82)-2-889-0310; phone: (+82)-2-880-6662; e-mail: ykchung@snu.ac.kr
Received: August 21, 2009; Revised: December 15, 2009; Published online: February 5, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900578.
Abstract: From cyclohexadienyl alkynes with a ter-
minal alkyne unit, double cyclopropanated products
were obtained in reasonable to high yields. For cy-
clohexadienyl alkynes substituted at the alkyne
unit, cyclopropanated products were obtained in
high yields. When a keto carbonyl group was intro-
duced to cyclohexadienyl alkynes with a substituted
alkyne, Alder-ene-type products were obtained in
reasonable to high yields.
cycle to enynes enhanced the reactivity or influenced
the reaction pathway (Scheme 1).[7] As Scheme 1
shows, the reaction patterns of cycloisomerization re-
Keywords: cyclohexadienyl alkynes; cycloisomeriza-
tion; cyclopropanation; iridium
Recently, the cycloisomerization of enynes has at-
tracted a lot of attention.[1] One of the reasons for this
is that a variety of cycloisomerized products can be
easily obtained depending upon the metal and the
Scheme 1.
substrate.[2] The reaction patterns depend on the actions depend on the structure of the substrates and
structure of the substrates and the nature of the cata- the nature of the catalytic systems. We expected that
lyst systems. For this reason various transition metal new type of transformations could be explored
complexes, such as those of Ti, Pt, Pd, Cu, Ru, Rh, through the interaction of alkynes and electrophilic
Co, Ir, W, and Au have been used as catalysts.[3] In transition metal complexes.
particular, the reaction patterns are highly influenced
The feasibility of the use of iridium compounds as
by a tether group.[4] However, in some cases, substan- catalysts in the cycloisomerization of enynes was first
tial structural variations are accommodated and dif- mentioned by Muraiꢀs group in 1994.[8] The first use
ferent functional groups found to be compatible.[5] of an iridium catalyst in the cycloisomerization of
Progress in the catalytic cycloisomerization of enynes enynes was reported by the same group in 2001.[6a]
with iridium is far behind that with rhodium, palladi- From enynes bearing a substituted alkyne moiety, 1,3-
um, platinum, or gold, although iridium catalysts have dienes were obtained as the products. Recently, Shi-
now been recognized as being particularly useful and bataꢀs group reported[6b,c] the iridium-catalyzed cyclo-
many of these reactions have recently been report-
G
ACHTUNGTREN[NUGN 4.1.0]heptenes.
ed.[6]
Many useful enynes have been used in the cycloiso- lyzed cycloisomerization of carbon-tethered 1,6-
merization. However, a new candidate to the list of enynes to (Z)-1-alkylidene-2-methylenecyclopentanes.
available enyne substrates still needs to be added. We Encouraged by the previous results, we studied the
recently found that the introduction of an olefinic iridium-catalyzed cycloisomerization reaction of cy-
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317

So Hee Sim et al.
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Table 1. Screening for optimum reaction conditions.[a]
Entry
Catalyst
[Ir(cod)Cl]2
Solvent
Temp. [oC]
Time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
N
toluene
toluene
toluene
toluene
THF
20
70
100
130
80
24
3
45 (54)[c]
77
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)Cl]2
(IPr)Ir
(cod)Cl[e]
IrCl3
R
E
ACHTUNGTRENNUNG
R
R
2.5
0.5
24
24
15
24
24
3
85[d]
94
92
71
76
CH2Cl2
DCE
20
80
N
A
U
toluene
toluene
toluene
toluene
toluene
130
130
100
100
100
0 (83)[c]
0 (85)[c]
50
9
10
11
12
[Rh
[Rh
[Ru
ACHTUNGTRENNUNG
A
A
24
24
52
50
[a]
0.34 mmol of 1a in 5 mL solvent was used.
Isolated yield.
The values in parenthesis represent the reactant recovered.
Reaction carried out with 1 atm CO.
IPr=N,N’-bis(2,6-diisopropylphenyl)imidazol)-2-ylidene.
[b]
[c]
[d]
[e]
clohexadienyl alkynes. Herein we report our prelimi- ened. At 1308C, the reaction time was shortened to
nary results. 30 min with 94% yield. Examination of the reaction
In the experience of our group, no reaction or de- medium led to the selection of toluene. In many tran-
composition had been observed for an enyne having sition metal-catalyzed reactions, the presence of
no substituents on the alkyne and alkene termini. carbon monoxide is helpful to the reaction.[6a,9] Thus,
Therefore, the use of an enyne with a terminal alkyne a cycloisomerization reaction under 1 atm of carbon
(1a) as a model substrate was from the outset some- monoxide was also studied. However, there was no
what unusual. However, cycloisomerization was stud- noticeable effect on the yield (85%). Thus, the opti-
ied using 1a as a model substrate and [IrACTHUNGTRENNUNG
catalyst in toluene.
ACHTUNGTRENNUNG
We screened various reaction conditions including 5 mL of toluene, 1308C, and 0.5 h. A brief survey of
the reaction temperature, the reaction time, and the different metal complexes (entries 10–12) such as
effect of carbon monoxide on the cycloisomerization [RhACHTUGNTRNE(UNNG cod)Cl]2 (50%), [RhACHUTTGNENRNUG(OAc)2]2 (52%), and [RuACHTUNGTRENNUNG
of 1a. The results are summarized in Table 1. When cymene)Cl2]2 (50%) indicated that [Ir
ACHTUNGTRENNUNG
the reaction was conducted at 208C for 1 day, a tetra- best catalyst of those examined.
cyclo[3.3.0.02,8.04,6]octane derivative, 1b, was obtained
We next investigated the cycloisomerization of cy-
in 45% with a recovery of the reactant (54%). Com- clohexadienyl alkynes with a terminal alkyne under
pound 1b was previously reported by us in the gold these optimized reaction conditions (Table 2).[10] The
N-heterocyclic carbene-catalyzed cycloisomerization reaction was highly dependent upon the tether group.
of 1a.[7c] As the reaction temperature increased, the When the tether atom was carbon (entries 1–6), the
yield of 1b increased and the reaction time was short- expected cage compound b was obtained in 56–95%
Table 2. Ir(I)-catalyzed cycloisomerization of cyclohexadienyl alkynes.[a]
Entry
Reactant
Product
Time [h]
0.5
Yield [%][b]
1
94
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Iridium(I)-Catalyzed Cycloisomerization of Cyclohexadienyl Alkynes
Table 2. (Continued)
Entry
Reactant
Product
Time [h]
0.5
Yield [%][b]
2
95
3
4
5
6
0.5
0.5
1
67
56
69
91
2
7
8
0.5
72 (12/60)
68 (32/36)
7
9
0.5
48
83
30
10
11
2
52
[a]
0.34 mmol of cyclohexadienyl alkyne and 2.5 mol% [Ir
Isolated yield.
ACHTUNGTRNEUN(NG cod)Cl]2 were reacted in 5 mL toluene at 1308C.
[b]
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319

So Hee Sim et al.
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exception to the general reaction product can be
easily seen. Thus, in the hope of finding a new reac-
tion pathway, we introduced a keto carbonyl to the
enyne substrates and studied their reaction in the
presence of the iridium catalyst (Scheme 2). When a
keto carbonyl was introduced to a carbon-tethered
enyne substrate with a phenyl substrate on the alkyne
terminus, an incomplete double cyclopropanation oc-
curred to give 12d in 49% yield. However, other keto
cyclohexedienyl alkynes with a heteroatom tether
provided the Alder-ene-type product (13e and 14e) in
85% and 35% yields, respectively, depending upon
the tether group, N-Ts and oxygen. According to the
Figure 1. X-ray crystal structure of 10d.
yield. However, when the tether group was changed NOE study of 13e and 14e, only the Z-isomer was ob-
to N-Ts (entry 7), a cyclopropanated product (7c) was served (see Supporting Information). A similar Alder-
obtained in 60% with the concomitant formation of a ene-type reaction was observed in the palladium-cata-
tetracyclooctane derivative (7b) in 12% yield. When a lyzed reaction of cyclopentenyl.[11]
methyl group was introduced to the propargylic
We also investigated the iridium-catalyzed cycloiso-
carbon of enynes to bring any steric effect (entry 8), a merization of various enynes with an internal alkyne.
slight increase of the yield (32%) of b was observed. Our preliminary study (Scheme 3) showed that the cy-
To our surprise, when an enyne substrate with a di-
ACHTUNGTRENNUNGsubstituted propargyl carbon was used as a substrate
(entry 9), only 9b was obtained in 83% yield as the
sole product. It seemed that disubstitution at the
propargyl carbon might protect a reaction pathway to
c and enhance the formation of b. When an enyne
with a phenyl-substituted alkyne and disubstitution at
the propargyl carbon was used as
a substrate
(entry 10), a new cycloisomerized product (10d) de-
rived from an incomplete double cyclopropanation
was formed in 30% yield. The formation of 10d was
1
confirmed by H and 13C NMR and by X-ray diffrac-
tion analysis (Figure 1).[10] However, a terminal cyclo-
hexadienyl alkyne (11a) with an oxygen tether atom
provided only 11c in 52% yield as the sole product
(entry 11).
In cycloisomerization reactions, a subtle change in
the substrate may lead to a different reaction path, re-
sulting in a different reaction product; therefore, an
Scheme 3. Ir(I)-catalyzed cyclopropanation of enynes.
Scheme 2. Ir(I)-catalyzed cycloisomerization of keto cyclohexadienyl alkynes.
320
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Adv. Synth. Catal. 2010, 352, 317 – 322

Iridium(I)-Catalyzed Cycloisomerization of Cyclohexadienyl Alkynes
cloisomerization reaction of various enynes with a di- Acknowledgements
A
triple
bond
provided
bicyclo-
This work was supported by the Korea Government
(MOEHRD) (KRF-2008-341-C00022) and the SRC/ERC
program of MOST/KOSEF (R11-2005-065). SHS thanks the
BK21 fellowship and Seoul Science Fellowship.
ACHTUNGTRENNUNG[4.1.0]heptanes. The reaction times and yields were
highly dependent upon the substrate. As already men-
tioned, Shibata et al.[6b] also reported the formation of
bicyclo
ic iridium species [20 mol% IrCl(CO)AHCUTNGTRENNUNG
24 mol% AgX (X=OTf or SbF6)] as a catalyst. Com-
pared to their system, our catalytic system used
2.5 mol% [IrACHTUNGTRENNUNG(cod)Cl]2 in the absence of any additive.
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allyl propargyl ether (18a) although the reaction time
is lengthened to 30 h. Thus, for the scope of available
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an internal alkyne to give bicycloACHTUNTRGNEUNG[4.1.0]heptenes. Fur-
ther synthetic applications of these reactions are
under investigation.
Experimental Section
General Procedure for Iridium(I)-Catalyzed
Cycloisomerization of Cyclohexadienyl Alkynes
To a flame-dried 10-mL Schlenk flask capped with a rubber
septum, toluene (5 mL) and [IrACHTNUGRTENUNG(cod)Cl]2 (5.3 mg, 2.5 mol%)
were added under a flow of N2. To the resulting mixture, 1a
(0.11 g, 0.34 mmol) was added under N2. The reaction mix-
ture was stirred at 1308C and was monitored by TLC. After
the reaction mixture had been cooled to room temperature,
the reaction mixture was filtered and all the solvent was
evaporated under reduced pressure. A flash column chroma-
tography on a silica gel eluting with hexane and ethyl ace-
tate (v/v, 10:2) gave the 2b; yield: 94%.
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