Remarkable Effect of Ethylene Gas in the Intramolecular Enyne Metathesis of Terminal Alkynes

Full text of DOI:10.1021/jo980896e

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082
J . Org. Chem. 1998, 63, 6082-6083
Rem a r k a ble Effect of Eth ylen e Ga s in th e
In tr a m olecu la r En yn e Meta th esis of Ter m in a l
Alk yn es
Sch em e 1
Miwako Mori,* Norikazu Sakakibara, and
Atsushi Kinoshita
Graduate School of Pharmaceutical Sciences,
Hokkaido University, Sapporo 060-0812, J apan
Sch em e 2
Received May 13, 1998
1
Metathesis reaction using molybdenum and ruthenium
2
carbene complexes is a very attractive method for the
synthesis of cyclized products.3 It provides a new methodol-
ogy for the synthesis of natural products, especially macro-
cyclic compounds. Enyne metathesis is also very interesting
and useful, and it is also applicable for the synthesis of
cyclized products.4 In intramolecular enyne metathesis,
the cyclized product having a diene moiety was obtained,
and in this reaction, the alkylidene part of alkene in enyne
migrates on the alkyne carbon. We have already reported
ruthenium-catalyzed enyne metathesis.6 In this reaction,
a substituent on the alkyne was required. When enyne 1a
having no substituent on alkyne was treated with 2a at rt,
only 13% yield of 3a was obtained, while enyne 1b having a
methyl group on the alkyne gave 89% yield of the desired
cyclized product 3b (Scheme 1).
,5
Ta ble 1. Rea ction of 1 w ith 2a or 2b u n d er Va r iou s
Con d ition sa
We reinvestigated ruthenium-catalyzed metathesis of
enyne having no substituent on the alkyne. When enyne
run
solvent
Ru mol % time (h)
under
Ar
Ar
Ar
yield (%)
1
2
3
4
5
benzene 2a
benzene 2b
1
1
1
1
3
22
22
22
22
13
15
21
90
99
1
a was treated with 2a , diene 3a was formed. In this
reaction, no increase in the product was seen on TLC after
several hours. It seems likely that the catalytic activity of
the ruthenium catalyst decreased, although the color of the
solution did not change. It was thought that the ruthenium
catalyst would further react with the vinyl group of diene 3
to produce ruthenacyclobutane 6. The retrocycloaddition of
CH2Cl2
CH2Cl2
2
2b
2b
2b
H2CdCH2
H CdCH
CH Cl2
2.5
2
2
a
All reactions were carried out at room temperature.
ruthenium complex 4 does not react with 3, and it should
react with 1 again.7
6
produced alkylidene carbene complex 7, which was coor-
dinated by the olefin of diene (Scheme 2).
In this reaction, methylidene ruthenium complex 4 reacts
with enyne 1 to give ruthenacyclobutane 5, which converts
into diene 3 and methylidene ruthenium complex 4. If this
At first, we examined the catalytic activity of benzylidene
ruthenium complex 2b compared with 2a . When a benzene
solution of 1a and 1 mol % of 2b was stirred at rt for 22 h,
the yield of 3a was almost the same (Table 1, run 2). When
the solvent was changed from benzene to CH2Cl2, the yield
of 3a was slightly improved. Surprisingly, when the reaction
was carried out under an atmosphere of ethylene gas for 22
6
reaction is carried out under ethylene gas, the generated
methylideneruthenium complex 4 reacts with ethylene to
produce ruthenacyclobutane 8, which is in a state of equi-
librium with methylidene ruthenium complex 4 and ethylene
gas (a so-called nonproductive process). Thus, methylidene
(
7) We have already reported that in the enyne metathesis ruthenium
(
1) Schrock, R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .; DiMare,
M.; O’Regan, M. J . Am. Chem. Soc. 1990, 112, 3875.
2) (a) Nguyen, S. T.; J ohnson, L. K.; Grubbs, R. H.; Ziller, J . W. J . Am.
carbene complex 2a should react at first with the alkyne part, not the alkene
part.5 However, the reaction rates of diene metathesis and enyne metath-
esis were almost same. Even if methylidene ruthenium complex 4 reacts
at first with the alkene part of 1, the same ruthenium carbene compelx 7
would be formed via ruthenacyclobutane 9, ruthenium carbene complex 10,
and ruthenacyclobutene 11. In this case, ethylene gas should be also
effective because 7 reacts with ethylene to produce 6, which produces
cyclized product 3 and methylidene carbene complex 4.
a
(
Chem. Soc. 1992, 114, 3974. (b) Nguyen, S. T.; Grubbs, R. H.; Ziller, J . W.
J . Am. Chem. Soc. 1993, 115, 9858. (c) Schwab, P.; France, M. B.; Ziller, J .
W.; Grubbs, R. H. Angew. Chem., Int. Ed. Engl. 1995, 34, 2039. (d) Schwab
P.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem. Soc. 1996, 118, 100.
(3) (a) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36,
2
4
036. (b) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995, 28,
46.
(
4) (a) Katz, T. J .; Sivavec, T. M. J . Am. Chem. Soc. 1985, 107, 737. (b)
Kim, S.-H.; Bowden, N.; Grubbs, R. H. J . Am. Chem. Soc. 1994, 116, 10801.
c) Chatani, N.; Morimoto, T.; Muto, T.; Murai, S.J . Am. Chem. Soc. 1994,
(
1
1
16, 6049. (d) Trost, B. M.; Tanoury, G. J . J . Am. Chem. Soc. 1988, 110,
636. (e) Mori, M.; Watanuki, S. J . Chem. Soc., Chem. Commun. 1992, 1082.
(
f) Watanuki, S.; Ochifuji, N.; Mori, M. Organometallics 1994, 13, 4129. (g)
Kim, S.-H.; Zuercher, W. J .; Bowden, N. B.; Grubbs, R. H. J . Org. Chem.
996, 61, 1073. (h) Barrett, A. G. M.; Baugh, S. P. D.; Braddock, D. C.;
Flack, K.; Gibson, V. C.; Procopiou, P. A. J . Chem. Soc., Chem. Commun.
997, 1375. (i) Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S. Organo-
metallics 1996, 15, 901.
5) (a) Kinoshita, A.; Mori, M. Synlett 1994, 1020; (b) J . Org. Chem. 1996,
1, 8356; (c) Heterocycles, 1997, 46, 287.
6) Kinoshita, A.; Sakakibara, N.; Mori, M. J . Am. Chem. Soc. 1997, 119,
2388.
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S0022-3263(98)00896-2 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/14/1998

Communications
Ta ble 2. En yn e Meta th esis u n d er a n Eth ylen e
J . Org. Chem., Vol. 63, No. 18, 1998 6083
Sch em e 3
a
Atm osp h er e
only 1 mol % of ruthenium carbene complex 2b was used
for this reaction at rt under an atmosphere of ethylene gas,
the desired cyclized diene 3 was obtained in an almost
quantitative yield. Ethylene gas was quite effective for the
formation of nitrogen heterocycles, carbocycles, and oxygen
heterocycles and for the formation of 6- and 7-membered
cyclic compounds. In the absence of ethylene gas, the
desired product was obtained in low yield, although the
conversion yield was good.
Since these products have a diene moiety, we tried to
synthesize isoquinoline derivative 10, which is a useful
heterocycle for the synthesis of biologically active substances,
from piperidine derivative 3b by the Diels-Alder reaction.
When a benzene solution of piperidine derivative 3b and
dimethyl acetylenedicarboxylate 9a was refluxed for 5 h,
isoquinoline derivative 10a was obtained in 83% yield. In
a similar manner, tricyclic compound 10b was obtained in
quantitative yield from 3b and 10b as a single product. The
stereochemistry of 10b was determined by an NOE experi-
ment (Scheme 3).
a
All reactions were carried out using 1 mol % of ruthenium
b
catalyst 2b in CH2Cl2. Yield in parentheses is that of recovered
material. 3 mol % of 2b was used.
c
h, the yield of 3a increased to 90% (run 4). The use of 3
mol % of 2b gave 3a in quantitative yield only after 2.5 h
run 5).
The reactions of various enynes 1 having no substituent
on the alkyne with ruthenium carbene complex 2b were
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
(
1
13
dures and spectral data ( H, C, and MS) for 1, 3, and 13a ,b (6
pages).
carried out, and the results are shown in Table 2. When
J O980896E