Ruthenium-catalyzed intramolecular [2+2+2] cycloaddition and tandem cross-metathesis of triynes and enediynes

Article abstract of DOI:10.1002/open.201300002

[2+2+2] Cycloadditions can be applied to specifically build up derivatives of benzene and cyclohexadiene and, therefore, have attracted much attention. Herein, we present an intramolecular [2+2+2] cycloaddition of triynes catalyzed by the firstgeneration Grubbs ruthenium complex (Ru gen-1), which can efficiently afford benzene derivatives in good yields under mild conditions. Moreover, we also report on a novel tandem cross-metathesis transformation of intramolecular enediynes also catalyzed by Ru gen-1, which has not been observed previously in related reports. On the basis of deuterium labeling experiments, a possible reaction mechanism is presented.

Full text of DOI:10.1002/open.201300002

DOI: 10.1002/open.201300002
Ruthenium-Catalyzed Intramolecular [2+2+2] Cycloaddition
and Tandem Cross-Metathesis of Triynes and Enediynes
Wei Yuan, Yin Wei, and Min Shi*[a]
[2+2+2] Cycloadditions can be applied to specifically build up
derivatives of benzene and cyclohexadiene and, therefore,
have attracted much attention. Herein, we present an intramo-
lecular [2+2+2] cycloaddition of triynes catalyzed by the first-
generation Grubbs ruthenium complex (Ru gen-1), which can
efficiently afford benzene derivatives in good yields under mild
conditions. Moreover, we also report on a novel tandem cross-
metathesis transformation of intramolecular enediynes also
catalyzed by Ru gen-1, which has not been observed previous-
ly in related reports. On the basis of deuterium labeling experi-
ments, a possible reaction mechanism is presented.
Introduction
Cycloisomerization and cycloaddition reactions of enyne sub-
strates have witnessed significant developments in the past
decade due to their convenience and versatility in constructing
complicated ring structures and useful intermediates in the
synthesis of natural products.[1] Among these myriad transfor-
mations, intramolecular/intermolecular [2+2+2] cycloadditions
of triynes and enediynes catalyzed by transition metals have
attracted even more attention, since these types of [2+2+2]
cycloadditions can be applied to specifically build up the deriv-
atives of benzene and cyclohexadiene.[2,3] However, there are
not many reports on such [2+2+2] additions cata-
using 1H NMR with 1,3,5-trimethoxybenzene as an internal
standard; Table 1, Entry 1). Using 5 mol% of Ru gen-1 as the
catalyst, afforded 2a in 74% yield (Table 1, Entry 2). The reac-
tion conditions were optimized, and the results are summa-
rized in Table 1. As shown, the examination of solvent effects
revealed that dichloromethane is the suitable solvent, giving
1
2a in 88% H NMR yield (80% isolated yield; Table 1, Entries 3–
7). Moreover, the yield of 2a decreased together with the cata-
lyst loading of Ru gen-1 from 10 to 5 mol% (Table 1, Entry 8).
On the basis of screening other ruthenium and rhodium cata-
lyzed by the Grubbs ruthenium complex when
searching through previous literature.[4–8] Herein, we
present an intramolecular [2+2+2] cycloaddition of
triynes catalyzed by the first-generation Grubbs
ruthenium complex (Ru gen-1), which can efficiently
afford benzene derivatives in good yields under mild
conditions. Moreover, we also disclose
a novel
tandem cross-metathesis transformation of intramo-
lecular enediynes catalyzed by Ru gen-1 in this
paper, which has not been observed previously in re-
lated reports.
Figure 1 shows the ruthenium catalysts that are
used in this work of intramolecular cycloaddition and
tandem cross-metathesis reactions of triynes and
enediynes. Ru gen-1 and Ru gen-2 are the first and
second generation of Grubbs ruthenium complexes
Figure 1. Ruthenium catalysts used in intramolecular cycloaddition and tandem cross-
metathesis reactions of triynes and enediynes (Mes: 2,4,6-trimethylphenyl).
[a] W. Yuan, Dr. Y. Wei, Prof. Dr. M. Shi
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
354 Fenglin Lu, Shanghai 200032 (P. R. China)
E-mail: Mshi@mail.sioc.ac.cn
that have been widely used in olefin metathesis. Ru-3 is the
Hoveyda–Grubbs catalyst that was developed in the Hoveyda
group.[9] Ru-4 is a modified Hoveyda–Grubbs catalyst devel-
oped by Zhan.[9c] Catalyst kits Ru-5 developed by Dixneuf’s
group has also been widely used in enyne metathesis.[10]
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/open.201300002.
Initial examination of the intramolecular [2+2+2] cycloaddi-
tion of triynes was performed by using triyne 1a (0.1 mmol) as
the substrate in the presence of Ru gen-1 (10 mol%), and we
found that the benzene derivative 2a was formed in 84%
yield within 12 h in styrene at room temperature (determined
ꢀ 2013 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons
Attribution Non-Commercial License, which permits use, distribution and
reproduction in any medium, provided the original work is properly
cited and is not used for commercial purposes.
ChemistryOpen 2012, 00, 1 – 7
ꢀ 2012 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

M. Shi et al.
1 has been changed to a vinyl group, under standard condi-
tions. Initial examination was performed by using enediyne
3a (0.1 mmol) as the substrate in the presence of
Ru gen-1 (10 mol%) in styrene at room temperature. As
shown in Table 3, we found that the intramolecular tandem
cross-metathesis took place, affording 4a in 27% isolated yield
(Table 3, Entry 1). The examination of solvent effects revealed
that 1,2-dichloroethane (DCE) is a suitable solvent for this
tandem cross-metathesis (Table 3, Entries 2–8). The other ruthe-
nium catalysts, such as Ru gen-2, Ru-3, Ru-4 and Ru-5, did not
produce the desired product under similar conditions (Table 3,
Entries 9–12). Moreover, the additive effects such as styrene,
Ti(OiPr)4, and hydroquinone have also been examined under
the tentatively optimized conditions, but no significant im-
provement could be observed (for detailed results, see Table
SI-1 in the Supporting Information). Eventually, we identified
that using DCE as the solvent with 10 mol% of catalyst loading
(Ru gen-1), 4a could be obtained in 52% isolated yield at
708C within 12 h, which served as the best reaction conditions
for this reaction (Table 3, Entry 13).
Table 1. Optimization of the reaction conditions for the [2+2+2] cyclo-
addition reactions of intramolecular triynes catalyzed by Ru gen-1.[a]
Entry
Catalyst
Catalyst [mol%]
Solvent
Yield 2a [%][b]
1
2
3
4
5
6
7
8
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru(PPh3)2CpCl
Rh(PPh3)3Cl
[Rh(CO)2Cl]2
[Rh(COD)Cl]2
Pd(PPh3)2Cl2
PtCl2
10
5
styrene
styrene
toluene
DCE
84
74
37[c]
39
38
–
88 (80)[c]
68
85
71
10
10
10
10
10
5
10
10
10
10
10
5
THF
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
9
10
11
12
13
14
complex
76[c]
–
Under the optimized reaction conditions, the substrate
scope and limitations of the reaction were also explored, and
the results are summarized in Table 4. As for substrates 3a and
3b bearing cyclopropane rings, the reaction proceeded
smoothly to give the corresponding products 4a and 4b in
52% and 54% yields, respectively (Table 4, Entries 1 and 2).
When enediyne substrates 3c–h (R1 =R2 =R3 =H; X=TsN, BsN,
O or C; Y=O or TsN) were employed as substrates, the corre-
sponding products 4c–h could be obtained in 55%–68%
yields, respectively (Table 4, Entries 3–8). However, using ene-
diyne substrate 3i or 3j, in which the terminal C atom of the
propargyl group carries a methyl or phenyl group, the reaction
gave complex product mixtures under the standard conditions
(Table 4, Entries 9 and 10). In the case of triyne substrates 3k
and 3l, in which one carbon chain has been extended as
a CH2CH2 moiety, the corresponding hexatriene derivatives 4k
and 4l were afforded in 67% or 75% yields, respectively,
rather than the cross-metathesis reaction products (Table 4, En-
tries 11 and 12). On the basis of previous literature, it could be
rationalized that the products 4k and 4l were derived from
the energetically favored 6p-electrocyclization of the corre-
sponding tandem cross-metathesis products.[12] Finally, using
enediyne substrate 3m, in which the terminal C atom of the
allyl group is attached to a phenyl group, no reaction occurred
under the standard conditions (Table 4, Entry 13).
–
[a] Reagents and conditions: triyne substrate 1a (0.2 mmol), catalyst, sol-
vent (2 mL), RT, 12 h under argon. [b] Yields were determined using
1H NMR and 1,3,5-trimethoxybenzene as an internal standard. [c] Isolated
yields. DCE: 1,2-dichloroethane, THF: tetrahydrofuran.
lysts, we found that Ru gen-1 is the most efficient catalyst for
this [2+2+2] cycloaddition, although 2a could be given in
85% yield, when Ru(PPh3)2CpCl (10 mol%) was employed as
the catalyst (Table 1, Entries 9–12). Pd(PPh3)2Cl2 or PtCl2 did not
catalyze this reaction under otherwise identical conditions
(Table 1, Entries 12–14). Thus, we identified that using dichloro-
methane as the solvent and 10 mol% of Ru gen-1 as the cata-
lyst, 2a could be obtained in the best yield (Table 1, Entry 7).
Under the optimized reaction conditions, the substrate
scope and limitations of the reaction were explored and the
results are summarized in Table 2. As for triyne substrates 1a–
c
bearing cyclopropane rings, the reactions proceeded
smoothly to give the corresponding products 2a–c in 80–86%
yields (Table 2, Entries 1–3). When triyne substrates 1d–g,
which do not have a cyclopropyl group, were employed as
substrates, the corresponding [2+2+2] cycloaddition products
2d–g could be obtained in 66%-94% yields (Table 2, Entries 4–
7). Furthermore, using triyne substrates 1h–k in which R1, R2
and R3 are different substituents (R1 or R2 =nPr or Ph, R3 =H;
R1 =R2 =H, R3 =Me or Ph) as the substrates, the desired prod-
ucts 2h–k were obtained in moderate to good yields ranging
from 55% to 92% (Table 2, Entries 8–11). Finally, in the case of
triyne substrate 1l, in which one carbon chain has been ex-
tended to a CH2CH2 moiety, the corresponding product 2l was
also formed in 92% yield (Table 2, Entry 12). Their structures
have been assigned by spectroscopic data. Moreover, product
2g is a known compound and its spectroscopic data are con-
sistent with those in the literature.[11]
It seems to us that the corresponding products 4a–h were
produced via a tandem cross-metathesis process, since Grubbs
ruthenium complex (Ru gen-1) is also an effective catalyst in
enyne metathesis.[4 h,4i] In order to gain more mechanistic in-
sights into the reaction, we conducted an isotope labeling ex-
periment to examine the reaction outcome by using dideuter-
ated [D]-3h (deuterium content=54%) as the reactant, and
the reaction was carried out under the standard conditions
(Scheme 1; for details, see the Supporting Information). It was
found that product [D]-4h could be obtained in 60% yield
along with 54% deuterium content, clearly suggesting a cross-
metathesis process.
Next, we attempted to explore the reaction outcome of ene-
diynes, in which one terminal propargyl group in substrate
&2
&
www.chemistryopen.org
ꢀ 2012 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemistryOpen 2012, 00, 1 – 7
ÝÝ
These are not the final page numbers!

Ruthenium-Catalyzed Reactions
Table 2. Substrate scope of the intramolecular [2+2+2] cycloaddition reactions of triynes catalyzed by Ru gen-1.[a]
Entry
Compound 1
Product 2
Yield 2
[%][b]
Entry
Compound 1
Product 2
Yield 2
[%][b]
1
1a
1b
2a
2b
80
85
7
1g
1h
2g
2h
95
83
2
8
3
4
1c
2c
86
77
9
1i
1j
2i
2j
55
90
1d
2d
10
5
6
1e
1 f
2e
2 f
94
66
11
12
1k
1l
2k
2l
58
92
[a] Reagents and conditions: triyne substrate 1 (0.2 mmol), Ru gen-1 (10 mol%), CH2Cl2 (2 mL), RT, 12 h under argon. [b] Isolated yields. Bs: bromobenzene-
sulfonyl, Ts: 4-toluenesulfonyl.
On the other hand, using dideuterated substrate [D]-1e
(deuterium content>80%) in the reaction afforded the corre-
sponding product [D]-2e in 89% yield along with 80% deuteri-
um content under the standard conditions (Scheme 1; for de-
tails, see the Supporting Information), suggesting a specific in-
tramolecular [2+2+2] cycloaddition process.
carbene intermediate C. Then, vinyl carbene intermediate C un-
dergoes intramolecular [2+2] cycloaddition with the second
alkyne moiety to give another ruthenacyclobutene D, which
again undergoes a ring opening process to give carbene inter-
mediate E. The reaction of intermediate E with the released di-
deuterated styrene gives the desired product [D]-4h as well as
the catalyst engaging in the next catalytic cycle (Scheme 2). It
should be noted that this intramolecular tandem cross-meta-
thesis of enediynes could also be initiated from the terminal
alkyne side (see Scheme SI-1 in the Supporting Information).
However, because none of the desired products were formed
in the cases of 3i, 3l and 3m, at the present stage, we
assumed that the mechanism shown in Scheme 2 might be
more reasonable.
On the basis of the above results, the deuterium labeling ex-
periments and the previous literature,[8,13] the mechanism for
the formation of 4 is outlined in Scheme 2 by using [D]-3h as
a reaction model. Initial reaction of Ru gen-1 with the olefin
moiety of [D]-3h generates methylene ruthenium intermedia-
te A along with the release of dideuterated styrene. The intra-
molecular [2+2] cycloaddition of carbene intermediate A with
the adjacent alkyne moiety produces ruthenacyclobutene B,
which undergoes a ring-opening process to give internal vinyl
ChemistryOpen 2012, 00, 1 – 7
ꢀ 2012 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemistryopen.org
&
3
&
ÞÞ
These are not the final page numbers!

M. Shi et al.
Table 3. Optimization of the reaction conditions for the intramolecular
tandem cross-metathesis reactions of enediynes.[a]
Entry
Catalyst
Solvent
T [8C]
Yield 4a [%][b]
1
2
3
4
5
6
7
8
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-1
Ru gen-2
Ru-3
styrene
CH2Cl2
THF
DMF
CH3CN
DCE
toluene
1,4-dioxane
CH2Cl2
DCE
CH2Cl2
CH2Cl2
DCE
RT
RT
RT
RT
RT
RT
RT
RT
RT
70
RT
RT
70
27[c]
15
10
–
–
37
16
complex
9
–
10
11
12
13
complex
–
Ru-4
Ru-5
Ru gen-1
–
63 (52)[c]
[a] Reagents and conditions: enyne substrate 3a (0.1 mmol), catalyst
(10 mol%), solvent (1.0 mL), 12 h under argon. [b] The yield was deter-
mined using 1H NMR and 1,3,5-trimethoxybenzene as an internal stan-
dard. [c] Isolated yields. Ts: 4-toluenesulfonyl, THF: tetrahydrofuran, DMF:
N,N-dimethylformamide, DCE: 1,2-dichloroethane.
Scheme 2. A possible reaction mechanism for the formation of [D]-4h
(Ts: 4-toluenesulfonyl).
Experimental Section
Detailed descriptions of the experimental procedures as well as
the spectroscopic data of the compounds shown in Tables 1–4 and
the 2D spectra of 4h and 4l (COSY, NOESY, HMQC, HMBC and
DEPT) are shown in the Supporting Information.
Ruthenium-catalyzed [2+2+2] intramolecular cycloaddition of
triynes: Substrate 1 (0.2 mmol), first-generation Grubbs catalyst
(10 mol%) and CH2Cl2 (2.0 mL) was added to a flame-dried Schlenk
tube, and the resulting solution was stirred at RT for 12 h. The re-
action mixture was concentrated in vacuo, and the residue was pu-
rified by flash silica gel column chromatography (pentane/EtOAc,
10:1–4:1).
Compound 2a: White solid (57 mg, 80%,): mp: 217–2198C;
1H NMR (CDCl3, 300 MHz, TMS): d=1.02 (dd, J1 =8.4 Hz, J2 =6.0 Hz,
2H, CH2), 1.23 (dd, J1 =8.4 Hz, J2 =6.0 Hz, 2H, CH2), 2.41 (s, 3H,
CH3), 4.40 (s, 2H, CH2), 4.56 (s, 2H, CH2), 5.11 (s, 2H, CH2), 7.03 (d,
J=7.8 Hz, 1H, Ar), 7.09 (d, J=7.8 Hz, 1H, Ar), 7.32 (d, J=8.1 Hz,
2H, Ar), 7.75 ppm (d, J=8.1 Hz, 2H, Ar); 13C NMR (CDCl3, 75 MHz,
TMS): d=11.2, 21.5, 50.5, 52.9, 68.3, 71.6, 120.6, 120.9, 126.8, 127.5,
129.9, 133.4, 136.3, 136.5, 139.3, 143.8 ppm; IR (CH2Cl2) n˜ =2956,
2923, 2855, 1597, 1493, 1465, 1345, 1163, 1098, 680 cmÀ1; MS (ESI):
m/z: 342.1 [M+H]+; HRMS (ESI): m/z [M+H]+ calcd for
C19H19NO3S: 341.1086, found: 341.1083.
Scheme 1. Isotope labeling experiments (Ts: 4-toluenesulfonyl).
In conclusion, we reported on intramolecular [2+2+2] cyclo-
addition and tandem cross-metathesis reactions of triynes and
enediynes, respectively, catalyzed by Ru gen-1 that can specifi-
cally produce the corresponding benzene derivatives 2 as well
as the conjugated triene derivatives 4 in moderate to good
yields. The real catalytic species is Ru-gen 1 rather than others.
A plausible reaction mechanism for the formation of 4 has also
been proposed on the basis of deuterium labeling experiments
and the previous literature. Further investigations on the
mechanistic details as well as the substrate scope of the reac-
tion are in progress.
Ruthenium-catalyzed intramolecular cross-metathesis of diynes:
Substrate 3 (0.2 mmol), first-generation Grubbs catalyst (10 mol%)
and 1,2-dichloroethane (2.0 mL) was added to
a flame-dried
Schlenk tube, and the resulting solution was stirred at 708C for
12 h. The reaction mixture was concentrated in vacuo, and the resi-
due was purified by flash silica gel column chromatography (pen-
tane/EtOAc, 10:1–4:1).
&4
&
www.chemistryopen.org
ꢀ 2012 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemistryOpen 2012, 00, 1 – 7
ÝÝ
These are not the final page numbers!

Ruthenium-Catalyzed Reactions
Table 4. Substrate scope of tandem intramolecular cross-metathesis reactions of enediynes catalyzed by Ru gen-1.[a]
Entry
Compound 3
Product 4
Yield 4
[%][b]
Entry
Compound 3
Product 4
Yield 4
[%][b]
1
3a
3b
4a
4b
55
54
7
3g
3h
4g
4h
61
55
2
8
3
4
5
6
3c
3d
3e
3 f
4c
4d
4e
4 f
68
68
64
68
9
3i
3j
3k
–
–
–
complex
complex
67
10
11[c]
–
4k
12[c]
3l
4l
75
13
3m
3m
–
N.R.[d]
[a] Reagents and conditions: substrate 3 (0.2 mmol), Ru gen-1 (10 mol%), DCE (2.0 mL), 708C, 12 h under argon. [b] Isolated yields. [c] Derived from a
6p-electrocyclization of the corresponding tandem cross-metathesis products. [d] No reaction. Bs: bromobenzenesulfonyl, Ts: 4-toluenesulfonyl.
Compound 4a: Colorless oil (54 mg, 68%): 1H NMR (CDCl3,
China ((973)-2009CB825300), and the National Natural Science
400 MHz, TMS): d=0.51 (dd, J1 =8.0 Hz, J2 =6.4 Hz, 2H, CH2), 0.93
(dd, J1 =8.0 Hz, J2 =6.4 Hz, 2H, CH2), 2.44 (s, 3H, CH3), 4.06 (t, J=
4.0 Hz, 2H, CH2), 4.26 (t, J=4.0 Hz, 2H, CH2), 4.75 (d, J=2.0 Hz, 2H,
CH2), 5.08 (d, J=18.0 Hz, 1H, =CH2), 5.21 (d, J=10.8 Hz, 1H, =CH2),
5.76 (t, J=2.0 Hz, 1H, =CH), 6.48 (dd, J1 =18.0 Hz, J2 =10.8 Hz, 1H,
=CH), 7.34 (d, J=8.0 Hz, 2H, Ar), 7.72 ppm (d, J=8.0 Hz, 2H, Ar);
13C NMR (CDCl3, 100 MHz, TMS): d=10.3, 21.5, 54.4, 57.4, 71.9, 73.4,
117.6, 126.87, 126.94, 127.4, 128.4, 129.9, 133.8, 134.9, 143.8 ppm;
Foundation of China (21102166, 20872162, 21072206, 20672127,
21121062 and 20732008) for financial support. We also thank Dr.
Chun-Yang Cao for his help with the analysis of NMR spectro-
scopic data.
Keywords: cross-metathesis · cycloaddition · enediynes · first-
generation Grubbs catalyst · triynes
IR (CH2Cl2): n˜ =2927, 2858, 1597, 1454, 1345, 1163, 1095, 817 cmÀ1
;
MS (ESI): m/z 344.1 [M+H]+; HRMS (ESI): m/z [M+H]+ calcd for
[1] For recent reviews, please see: a) I. J. S. Fairlamb, Angew. Chem. 2004,
116, 1066–1070; Angew. Chem. Int. Ed. 2004, 43, 1048–1052; b) V. Mi-
chelet, P. Y. Toullec, J. P. Genꢁt, Angew. Chem. 2008, 120, 4338–4386;
Angew. Chem. Int. Ed. 2008, 47, 4268–4315.
C19H21NO3S: 343.1242, found: 343.1248.
[2] For selected reviews of [2+2+2] cycloadditions, please see: a) J. A.
Varela, C. Saꢂ, Chem. Rev. 2003, 103, 3787–3801; b) S. Kotha, E. Brah-
machary, K. Lahiri, Eur. J. Org. Chem. 2005, 4741–4767; c) V. Gandon, C.
Aubert, M. Malacria, Chem. Commun. 2006, 2209–2217; d) P. R. Cho-
pade, J. Louie, Adv. Synth. Catal. 2006, 348, 2307–2327; e) B. Heller, M.
Acknowledgement
We thank the Shanghai Municipal Committee of Science and
Technology (11JC1402600), National Basic Research Program of
ChemistryOpen 2012, 00, 1 – 7
ꢀ 2012 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemistryopen.org
&
5
&
ÞÞ
These are not the final page numbers!

M. Shi et al.
Hapke, Chem. Soc. Rev. 2007, 36, 1085–1094; f) J. A. Varela, C. Saꢂ, Syn-
lett 2008, 2571–2578; g) T. Shibata, K. Tsuchikama, Org. Biomol. Chem.
2008, 6, 1317–1323; h) G. Domꢃnguez, J. Perez-Castells, Chem. Soc. Rev.
2011, 40, 3430–3444; i) N. Weding, M. Hapke, Chem. Soc. Rev. 2011, 40,
4525–4538; j) Y. Shibata, K. Tanaka, Synthesis 2012, 44, 323–350.
A. L. Vila, R. Drozdzak, P. V. D. Voort, F. Verpoort, Chem. Soc. Rev. 2009,
38, 3360–3372; f) M. D. McReynolds, J. M. Dougherty, P. R. Hanson,
Chem. Rev. 2004, 104, 2239–2258; g) A. Deiters, S. F. Martin, Chem. Rev.
2004, 104, 2199–2238; h) Handbook of Metathesis (Ed.: R. H. Grubbs),
Wiley-VCH, Weinheim, Germany, 2003; i) A. Fꢅrstner, Angew. Chem.
2000, 112, 3140–3172; Angew. Chem. Int. Ed. 2000, 39, 3012–3043.
[6] For selected reviews on olefin metathesis in natural product synthesis,
please see: a) A. H. Hoveyda, S. J. Malcolmson, S. J. Meek, A. R. Zhugra-
lin, Angew. Chem. 2010, 122, 38–49; Angew. Chem. Int. Ed. 2010, 49,
34–44; b) H. Clavier, K. Grela, A. Kirschning, M. Mauduit, S. P. Nolan,
Angew. Chem. 2007, 119, 6906–6922; Angew. Chem. Int. Ed. 2007, 46,
6786–6801; c) K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew. Chem. 2005,
117, 4564–4601; Angew. Chem. Int. Ed. 2005, 44, 4490–4527.
[7] For the first example of enyne metathesis, please see: T. J. Katz, T. M. Si-
vavec, J. Am. Chem. Soc. 1985, 107, 737–738.
[8] Recent reviews on enyne metathesis: a) M. Mori, Adv. Synth. Catal.
2007, 349, 121–135; b) H. Villar, M. Frings, C. Bolm, Chem. Soc. Rev.
2007, 36, 55–66; c) S. T. Diver, A. J. Giessert, Chem. Rev. 2004, 104,
1317–1382; d) M. Mori in Ene-yne Metathesis in Handbook of Metathesis,
Vol. 2 (Ed.: R. H. Grubbs), Wiley-VCH, Weinheim, Germany, 2003 p. 176;
e) C. S. Poulsen, R. Madsen, Synthesis 2003, 1, 1–18; f) J. J. Lippstreu,
B. F. Straub, J. Am. Chem. Soc. 2005, 127, 7444–7457.
[9] For Hoveyda–Grubbs catalyst, see: a) J. S. Kingsbury, J. P. A. Harrity, P. J.
Bonitatebus, A. H. Hoveyda, J. Am. Chem. Soc. 1999, 121, 791–799;
b) S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem.
Soc. 2000, 122, 8168–8179; for Zhan’s catalyst, see: c) Z.-Y. Zhan, WO
Patent 2007003135, 2007.
[10] D. Sꢁmeril, C. Bruneau, P. H. Dixneuf, Adv. Synth. Catal. 2002, 344, 585–
595.
[11] a) Y. Yamamoto, T. Arakawa, R. Ogawa, K. Itoh, J. Am. Chem. Soc. 2003,
125, 12143–12160; b) A. Geny, N. Agenet, L. Iannazzo, M. Malacria, C.
Aubert, V. Gandon, Angew. Chem. 2009, 121, 1842–1845; Angew. Chem.
Int. Ed. 2009, 48, 1810–1813.
[3] For more recent papers on [2+2+2] cycloaddition, please see: cata-
lyzed by Rh: a) L. Garcia, A. Roglans, R. Laurent, J. P. Majoral, A. Pla-Quin-
tana, A. M. Caminade, Chem. Commun. 2012, 48, 9248–9250; b) A.
Dachs, A. Pla-Quintana, T. Parella, M. Solꢄ, A. Roglans, Chem. Eur. J.
2011, 17, 14493–14507; c) N. Sakiyama, D. Hojo, K. Noguchi, K. Tanaka,
Chem. Eur. J. 2011, 17, 1428–1432; d) M. Kobayashi, T. Suda, K. Noguchi,
K. Tanaka, Angew. Chem. 2011, 123, 1702–1705; Angew. Chem. Int. Ed.
2011, 50, 1664–1667; e) F. Mori, N. Fukawa, K. Noguchi, K. Tanaka, Org.
Lett. 2011, 13, 362–365; f) N. Nicolaus, S. Strauss, J. M. Neudorfl, A.
Prokop, H. G. Schmalz, Org. Lett. 2009, 11, 341–344; g) B. Bennacer, M.
Fujiwara, S. Y. Lee, I. Ojima, J. Am. Chem. Soc. 2005, 127, 17756–17767;
catalyzed by Ir: h) G. Onodera, Y. Shimizu, J. Kimura, J. Kobayashi, Y. Ebi-
hara, K. Kondo, R. Takeuchi, J. Am. Chem. Soc. 2012, 134, 10515–10531;
catalyzed by Nb: i) Y. Satoh, Y. Obora, Org. Lett. 2011, 13, 2568–2571;
catalyzed by Ni: j) Z. Z. Qiu, Z. W. Xie, Angew. Chem. 2009, 121, 5839–
5842; Angew. Chem. Int. Ed. 2009, 48, 5729–5732; k) N. Saito, K. Shiota-
ni, A. Kinbara, Y. Sato, Chem. Commun. 2009, 4284–4286; catalyzed by
Co: l) A. Geny, S. Gaudrel, F. Slowinski, M. Amatore, G. Chouraqui, M.
Malacria, C. Aubert, V. Gandona, Adv. Synth. Catal. 2009, 351, 271–275;
m) G. Hilt, A. Paul, K. Harms, J. Org. Chem. 2008, 73, 5187–5190; n) F.
Slowinski, C. Aubert, M. Malacria, Adv. Synth. Catal. 2001, 343, 64–67.
[4] For more recent papers on [2+2+2] cycloaddition catalyzed by Ru,
please see: a) N. Saito, T. Ichimaru, Y. Sato, Asian J. Chem. 2012, 7,
1521–1523; b) C. Y. Wu, Y. C. Lin, P. T. Chou, Y. Wang, Y. H. Liu, Dalton
Trans. 2011, 40, 3748–3753; c) S. Garcꢃa-Rubꢃn, J. A. Varela, L. Castedo,
C. Saꢂ, Chem. Eur. J. 2008, 14, 9772–9778; d) J. A. Varela, S. G. Rubꢃn, L.
Castedo, C. Saꢂ, J. Org. Chem. 2008, 73, 1320–1332; e) Y. Yamamoto, K.
Hattori, H. Nishiyama, J. Am. Chem. Soc. 2006, 128, 8336–8340; f) M.
Mori, N. Saito, D. Tanaka, M. Takimoto, Y. Sato, J. Am. Chem. Soc. 2003,
125, 5606–5607; g) D. Tanaka, Y. Sato, M. Mori, J. Am. Chem. Soc. 2007,
129, 7730–7731; h) M. Mori, Top. Organomet. Chem. 1999, 1, 133–154;
i) S. J. Connon, S. Blechert, Angew. Chem. 2003, 115, 1944–1968; Angew.
Chem. Int. Ed. 2003, 42, 1900–1923.
[12] a) E. N. Marvell, C. Hilton, M. Cleary, J. Org. Chem. 1983, 48, 4272–4275;
b) T. L. Gilchrist, R. J. Summersell, J. Chem. Soc. Perkin Trans. 1 1988,
2603–2606; c) X. H. Deng, L. S. Liebeskind, J. Am. Chem. Soc. 2001, 123,
7703–7704.
[13] Z.-B. Zhu, M. Shi, Org. Lett. 2010, 12, 4462–4465.
[5] Recent reviews on olefin metathesis: a) S. P. Nolan, H. Clavier, Chem.
Soc. Rev. 2010, 39, 3305–3316; b) G. C. Vougioukalakis, R. H. Grubbs,
Chem. Rev. 2010, 110, 1746–1787; c) A. M. Lozano-Vila, S. Monsaert, A.
Bajek, F. Verpoort, Chem. Rev. 2010, 110, 4865–4909; d) C. Samojłowicz,
M. Bieniek, K. Grela, Chem. Rev. 2009, 109, 3708–3742; e) S. Monsaert,
Received: January 22, 2013
Published online on && &&, 0000
&6
&
www.chemistryopen.org
ꢀ 2012 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemistryOpen 2012, 00, 1 – 7
ÝÝ
These are not the final page numbers!

FULL PAPERS
Back to generation one! Catalyzed by
the first-generation Grubbs ruthenium
complex, intramolecular [2+2+2] cyclo-
addition of triynes to their benzene de-
rivatives 2 and tandem cross-metathesis
reactions of enediynes to their conju-
gated triene derivatives 4 perform
W. Yuan, Y. Wei, M. Shi*
&& – &&
Ruthenium-Catalyzed Intramolecular
[2+2+2] Cycloaddition and Tandem
Cross-Metathesis of Triynes and
Enediynes
smoothly in moderate to good yields
under mild conditions. A possible reac-
tion mechanism is presented on the
basis of deuterium-labeling results.
ChemistryOpen 2012, 00, 1 – 7
ꢀ 2012 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemistryopen.org
&
7
&
ÞÞ
These are not the final page numbers!