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Novel synthesis of lactam from alkyne having amide in a tether using fischer chromium carbene complex
Terrahedron
Lrrrers,
Pergamon
Vol. 36, No. 52. pp. 9501-9504, 1995 ~~sevier Smnce Ltd Printed in Great Britam
0040.x)39/95
$9.50+0.00
0040-4039(95)02058-6
Novel
Synthesis Using
of Lactam Fischer Nagisa
from
Alkyne
Chromium Ochifuji
Having
Carbene
and Miwako
Amide
in a Tether
Complex
Mori*
Faculty of PharmaceuticalSciences.Hokkaido University, Sapporo 060, Japan
A novel lactam synthesisfrom alkyne having amidein atether wasdeveloped. The reaction proceedsGa a vinylketenecomplex generatedfrom alkyne andFischerchromium carbenecomplex,andthe lactam ring was fomled from carbon monoxide, alkyne carbon and nitrogen of tosylam& The four-. five, six-. and seven-memberedlactams havmg a substituentat the a-position were obtained in good
Abstract:
yields.
The [2+2+2] cocyclization of diyne and Fischer chromium carbene complex is very interesting and useful for the synthesis of fused phenol derivatives.’ Recently, we reported the syntheses of isoindoline and isoquinoline derivatives using this procedure.’ During the course of this study, we investigated the substituent effect on the alkyne carbon of diyne in the controlling the regioselectivity. When a THF solution of diyne la (n=l) and Fischer chromium carbene complex 2 was refluxed for 1 h, isoindoline 4a was obtained in 84% yield as the sole product after treatment with [FeCl,(DMF),J[FeCl,].’ However, a similar treatment of 1 b with 2 gave isoquinoline 4b in only 10% yield. It was very surprising to find that the main products were five-membered lactams 5 and 6 (43% yield, 1:l ratio of 5 to 6). and no tosyl group was found in these structures. OEt TsN/4TMS Idi% la n=l lbn=2
‘)
:cHq)T;:f;:;
h2
2)
[FeCl2WF)dFeCI41
t
TsN
1 ti n
3
Possible ,
’ 4
from
:MSOH
la lb
Me 64% 10%
22%
Mechanism =
TsN
TMS
2
,
=
,
TMS
=
TMS
TSN
z
lb
8
J 5and6
4 Scheme
9501
1
21%
9502
Compound 4 is obtained from vinylcarbene complex 7 produced by the reaction of terminal alkyne of 1 with chromium carbene complex 2. In the reaction of lb (n=2) with 2, formation of six-membered ring is not easier than that of the five-membered ring. As it was generally accepted that vinylcarbene complex 7 is in a state of equilibrium with the ketene complex 8, the tosylamide moiety of 8 reacts with the vinylketene to give lactams5 and6.4 On the basis of these results, it was expected that a novel lactam synthesis from alkyne could be developed.5 When a THF solution of 9a (1 .O equiv. ) and chromium carbene complex 2 (1.2 equiv.) was refluxed for 1 h, the desired lactam 10a was obtained in 53% yield after treatment with 3. In order to improve the yield of the desired lactam lOa, the reaction was carried out under various conditions (Table 1). It was found that the concentrations of the substrate and chromium carbene complex affect the yield of the desired product 1Oa (Table I, runs 1-3). The use of benzene or isopropyl ether as the solvent did not give good results, but the yield was improved to 85% when CH,CN was used (run 6). In a similar manner, compound 9b was treated with 2 in CH,CN followed by treatment with 10% HCl to give lactam lob, but the yield was modest (74%). The results indicate that lactam 10a could be synthesized from alkyne having a tosyl amide group in a tether and the lactam ring was formed from alkyne carbon, carbon monoxide and nitrogen of the tosyl amide moiety. This reaction was further applied to the synthesis of six- and seven-membered lactams, and the desired lactams 14 and 15 were obtained in high yields from the corresponding alkynes 12 and 13.
9a. R=Ts 9b; R=Z Table Run 1
1 Reaction Solvent THF
10a fob,
of 9a with 2 under Cow.
various
( mM ) Temp.
74%
conditions ( “C )Time
(h)Yield
of 1Oa
190
reflux
1
53% 60
2
THF
30
reflux
1
3
THF
6
reflux
1
72
4
i-PrzO
6
reflux
1
<14
5
PhH
6
70
1
42
6
CH&N
6
70
2
65
Ts-NY-P r; 11,
12, 13,
n=O n=2 n=3
14
62% Scheme
15 2
64%
16
16%
9503
Even in the case of the formation of four-membered lactam 16, the reaction of N-tosyl propargylamme 11 with 2 proceeded in CH,CH,CN at 80 ‘C to give the desired p-lactam 16, though the yield was only 16%.6.7 To confii the N-Ts bond fission in the formation of a lactam ring, compound 9c was treated with chromium carbene complex 2 in a similar manner. As a result, lactam 17 was obtained in 37% yield along Compound 18 is quite interesting with lactam 18 having a tosyl group at the 3-position in 13% yield. because the tosyl group of 9 c migrates from nitrogen to alkyne carbon. On the basis of these results, two reaction pathways can be considered for the formation of the lactam ring. One route is a nucleophilic addition of tosylamide to the vinylketene moiety of complex 20, and the other route is an oxidative addition of the NR part of amide to a low-valent chromium complex.’ The fact that lactam 18 is obtained from complex 2 3 by reductive elimination would support the latter mechanism. 1) 2, CH$N
70”c’1
T&,,d 2)
h*
h=
a
3
ile 17
9c Plausible
Reaction
+
& fk? 18
37%
13%
Mechanism
9
tI
20
oxidative addition
t
reductive elimination
)
insertion I
/\
Scheme
3
R2
Ln
R2
22
23
Thus, the reactions of tosylamides 9d, 9e, and 9f, having a silyl group on nitrogen with chromium carbene complex 2 were tried because the N-silyl group would oxidatively add to the low-valent metal complex. The desired lactam ring was formed in each case and the reaction of tosylamide 9f having a TMS group on nitrogen with 2 gave a good result (Table 2). In the cases of the tosylamides having TBS and TES groups on nitrogen, p-elimination from complex 23 would occur to give unsaturated compound 24. The formation of compounds 5, 6, and 17 can be also explained as p-elimination products. Table
Ts-N/-,/ I
1) 2, WCN
SiRlR2R3
-a’a 2) 3
9d, 9e, 9f
‘:
TS
” 10
Run 1 2
2 Reactions
SiRlRzR: 3 t-BuMe2 Et3
of alkynes
9d 9e
9 with 2
Yield
(% )
10 0 0
24 43 49
‘Silyl amide 91 was prepared in situ. The reaction mixture was treated with 10% HCI.
9504
In the formation of 4-membered lactam, the yield of 16 was improved to 50% when 11 was treated with Me,SiCl and BuLi in sihc and then the reaction of chromium carbene complex 2 with silated amide 25 was carried out. Ts-N\~
Me3SiClU.l
il
BuLi (1.05
9.) eq.) 25
11
Scheme
16
50%
5
Two carbene carbons (ethoxymethyl The remarkable characteristics of this reaction are as follows. A lactam ring is formed from carbene and carbon monoxide) are inserted into alkyne carbons, respectively. Lactams with various ring sizes (4-7 alkyne carbon, carbon monoxide and nitrogen of tosylamide. membered lactams) can be synthesized by elongation of the methylene part on the alkyne carbon. Further studies on applications of this reaction are in progress. Acknowledgment: This work was supported by Grant-in-Aid for Scientific Research on Priority Area of Reactive Grganometallics No. 05236106 from the Ministry of Education, Science and Culture, Japan and the A&i Glass Foundation. References and Notes 1 a) Bao, J.: Wulff, W. D.; Dragisich, V.; Wenglowsky, S.; Ball, R. G. J. Am. Chem. Sot.. 1994, 116, 7616. b) Wulff, W. D.; Kaesler, R. D.; Peterson, G. A.; Tang, P. -C. J. Am. Chem. Sot., 1985. 107, 1060. c) Xu Y. -C. Wulff, W. D. J. Org. C/rem., 1987, 52, 3263. d) Sivavec T. M.: Katz, T. J. Tetrahedron Lm.. 1985, 26. 2159. 2 Mori, M.; Kuriyama, K .; Ochifuji, N.; Watanuki, S. Chem. Lett., 1995, 6 1.5. 3. Tobinaga, S.; Kotani, E. J. Am. Chem. Sot., 1972, 94, 309. 4. Chelain, E.; Parlier, A.; Audouuin. M.; Rudler, H.; Damn, J-C.; Vaissermann, J. J. Am. Chem. Sot., 1993,115, 10568. 5. Efficient synthesis of lactams by intramolecular trapping of ketene was reported. MaGee, D. I.; Ramaseshan. M. Synlett., 1994. 743. 6. Hegedus reported that the reaction of imine with Fischer chromium carbene complex upon photolysis afforded B-lactam in good yield. Hegedus, L. S. Act. Chem. Res., 1995, 28. 299 and references therein. 7. The other products: were lactone 26 and ester 27. Cf. Challener, C. A.; Wulff, W. D.; Anderson, B. A.; Chamberlin, S.; Faron, K. L.; Kim, 0. K.; Murray, C. K.; Xu, Y-C.; Yang, D. C.; Darling, S. D. J. Am. Chem. Sot., 1993, 115, 1359.
26, 24%
8.
27,
11%
When 4-N-methyl-N-p-toluenesulfonylaminobutylic acid was converted into acid chloride by treatment with (CoCl), in CH,Cl, and then the chloride was treated with NEt, in THF at 0 r. the ketene dimer was obtained in 13% yield. Though the reaction was carried out upon heating, no cyclized product was obtained.
(Received in Japan 14 September 1995; revised 20 October 1995;
accepted
27 October
1995)
Lrrrers,
Pergamon
Vol. 36, No. 52. pp. 9501-9504, 1995 ~~sevier Smnce Ltd Printed in Great Britam
0040.x)39/95
$9.50+0.00
0040-4039(95)02058-6
Novel
Synthesis Using
of Lactam Fischer Nagisa
from
Alkyne
Chromium Ochifuji
Having
Carbene
and Miwako
Amide
in a Tether
Complex
Mori*
Faculty of PharmaceuticalSciences.Hokkaido University, Sapporo 060, Japan
A novel lactam synthesisfrom alkyne having amidein atether wasdeveloped. The reaction proceedsGa a vinylketenecomplex generatedfrom alkyne andFischerchromium carbenecomplex,andthe lactam ring was fomled from carbon monoxide, alkyne carbon and nitrogen of tosylam& The four-. five, six-. and seven-memberedlactams havmg a substituentat the a-position were obtained in good
Abstract:
yields.
The [2+2+2] cocyclization of diyne and Fischer chromium carbene complex is very interesting and useful for the synthesis of fused phenol derivatives.’ Recently, we reported the syntheses of isoindoline and isoquinoline derivatives using this procedure.’ During the course of this study, we investigated the substituent effect on the alkyne carbon of diyne in the controlling the regioselectivity. When a THF solution of diyne la (n=l) and Fischer chromium carbene complex 2 was refluxed for 1 h, isoindoline 4a was obtained in 84% yield as the sole product after treatment with [FeCl,(DMF),J[FeCl,].’ However, a similar treatment of 1 b with 2 gave isoquinoline 4b in only 10% yield. It was very surprising to find that the main products were five-membered lactams 5 and 6 (43% yield, 1:l ratio of 5 to 6). and no tosyl group was found in these structures. OEt TsN/4TMS Idi% la n=l lbn=2
‘)
:cHq)T;:f;:;
h2
2)
[FeCl2WF)dFeCI41
t
TsN
1 ti n
3
Possible ,
’ 4
from
:MSOH
la lb
Me 64% 10%
22%
Mechanism =
TsN
TMS
2
,
=
,
TMS
=
TMS
TSN
z
lb
8
J 5and6
4 Scheme
9501
1
21%
9502
Compound 4 is obtained from vinylcarbene complex 7 produced by the reaction of terminal alkyne of 1 with chromium carbene complex 2. In the reaction of lb (n=2) with 2, formation of six-membered ring is not easier than that of the five-membered ring. As it was generally accepted that vinylcarbene complex 7 is in a state of equilibrium with the ketene complex 8, the tosylamide moiety of 8 reacts with the vinylketene to give lactams5 and6.4 On the basis of these results, it was expected that a novel lactam synthesis from alkyne could be developed.5 When a THF solution of 9a (1 .O equiv. ) and chromium carbene complex 2 (1.2 equiv.) was refluxed for 1 h, the desired lactam 10a was obtained in 53% yield after treatment with 3. In order to improve the yield of the desired lactam lOa, the reaction was carried out under various conditions (Table 1). It was found that the concentrations of the substrate and chromium carbene complex affect the yield of the desired product 1Oa (Table I, runs 1-3). The use of benzene or isopropyl ether as the solvent did not give good results, but the yield was improved to 85% when CH,CN was used (run 6). In a similar manner, compound 9b was treated with 2 in CH,CN followed by treatment with 10% HCl to give lactam lob, but the yield was modest (74%). The results indicate that lactam 10a could be synthesized from alkyne having a tosyl amide group in a tether and the lactam ring was formed from alkyne carbon, carbon monoxide and nitrogen of the tosyl amide moiety. This reaction was further applied to the synthesis of six- and seven-membered lactams, and the desired lactams 14 and 15 were obtained in high yields from the corresponding alkynes 12 and 13.
9a. R=Ts 9b; R=Z Table Run 1
1 Reaction Solvent THF
10a fob,
of 9a with 2 under Cow.
various
( mM ) Temp.
74%
conditions ( “C )Time
(h)Yield
of 1Oa
190
reflux
1
53% 60
2
THF
30
reflux
1
3
THF
6
reflux
1
72
4
i-PrzO
6
reflux
1
<14
5
PhH
6
70
1
42
6
CH&N
6
70
2
65
Ts-NY-P r; 11,
12, 13,
n=O n=2 n=3
14
62% Scheme
15 2
64%
16
16%
9503
Even in the case of the formation of four-membered lactam 16, the reaction of N-tosyl propargylamme 11 with 2 proceeded in CH,CH,CN at 80 ‘C to give the desired p-lactam 16, though the yield was only 16%.6.7 To confii the N-Ts bond fission in the formation of a lactam ring, compound 9c was treated with chromium carbene complex 2 in a similar manner. As a result, lactam 17 was obtained in 37% yield along Compound 18 is quite interesting with lactam 18 having a tosyl group at the 3-position in 13% yield. because the tosyl group of 9 c migrates from nitrogen to alkyne carbon. On the basis of these results, two reaction pathways can be considered for the formation of the lactam ring. One route is a nucleophilic addition of tosylamide to the vinylketene moiety of complex 20, and the other route is an oxidative addition of the NR part of amide to a low-valent chromium complex.’ The fact that lactam 18 is obtained from complex 2 3 by reductive elimination would support the latter mechanism. 1) 2, CH$N
70”c’1
T&,,d 2)
h*
h=
a
3
ile 17
9c Plausible
Reaction
+
& fk? 18
37%
13%
Mechanism
9
tI
20
oxidative addition
t
reductive elimination
)
insertion I
/\
Scheme
3
R2
Ln
R2
22
23
Thus, the reactions of tosylamides 9d, 9e, and 9f, having a silyl group on nitrogen with chromium carbene complex 2 were tried because the N-silyl group would oxidatively add to the low-valent metal complex. The desired lactam ring was formed in each case and the reaction of tosylamide 9f having a TMS group on nitrogen with 2 gave a good result (Table 2). In the cases of the tosylamides having TBS and TES groups on nitrogen, p-elimination from complex 23 would occur to give unsaturated compound 24. The formation of compounds 5, 6, and 17 can be also explained as p-elimination products. Table
Ts-N/-,/ I
1) 2, WCN
SiRlR2R3
-a’a 2) 3
9d, 9e, 9f
‘:
TS
” 10
Run 1 2
2 Reactions
SiRlRzR: 3 t-BuMe2 Et3
of alkynes
9d 9e
9 with 2
Yield
(% )
10 0 0
24 43 49
‘Silyl amide 91 was prepared in situ. The reaction mixture was treated with 10% HCI.
9504
In the formation of 4-membered lactam, the yield of 16 was improved to 50% when 11 was treated with Me,SiCl and BuLi in sihc and then the reaction of chromium carbene complex 2 with silated amide 25 was carried out. Ts-N\~
Me3SiClU.l
il
BuLi (1.05
9.) eq.) 25
11
Scheme
16
50%
5
Two carbene carbons (ethoxymethyl The remarkable characteristics of this reaction are as follows. A lactam ring is formed from carbene and carbon monoxide) are inserted into alkyne carbons, respectively. Lactams with various ring sizes (4-7 alkyne carbon, carbon monoxide and nitrogen of tosylamide. membered lactams) can be synthesized by elongation of the methylene part on the alkyne carbon. Further studies on applications of this reaction are in progress. Acknowledgment: This work was supported by Grant-in-Aid for Scientific Research on Priority Area of Reactive Grganometallics No. 05236106 from the Ministry of Education, Science and Culture, Japan and the A&i Glass Foundation. References and Notes 1 a) Bao, J.: Wulff, W. D.; Dragisich, V.; Wenglowsky, S.; Ball, R. G. J. Am. Chem. Sot.. 1994, 116, 7616. b) Wulff, W. D.; Kaesler, R. D.; Peterson, G. A.; Tang, P. -C. J. Am. Chem. Sot., 1985. 107, 1060. c) Xu Y. -C. Wulff, W. D. J. Org. C/rem., 1987, 52, 3263. d) Sivavec T. M.: Katz, T. J. Tetrahedron Lm.. 1985, 26. 2159. 2 Mori, M.; Kuriyama, K .; Ochifuji, N.; Watanuki, S. Chem. Lett., 1995, 6 1.5. 3. Tobinaga, S.; Kotani, E. J. Am. Chem. Sot., 1972, 94, 309. 4. Chelain, E.; Parlier, A.; Audouuin. M.; Rudler, H.; Damn, J-C.; Vaissermann, J. J. Am. Chem. Sot., 1993,115, 10568. 5. Efficient synthesis of lactams by intramolecular trapping of ketene was reported. MaGee, D. I.; Ramaseshan. M. Synlett., 1994. 743. 6. Hegedus reported that the reaction of imine with Fischer chromium carbene complex upon photolysis afforded B-lactam in good yield. Hegedus, L. S. Act. Chem. Res., 1995, 28. 299 and references therein. 7. The other products: were lactone 26 and ester 27. Cf. Challener, C. A.; Wulff, W. D.; Anderson, B. A.; Chamberlin, S.; Faron, K. L.; Kim, 0. K.; Murray, C. K.; Xu, Y-C.; Yang, D. C.; Darling, S. D. J. Am. Chem. Sot., 1993, 115, 1359.
26, 24%
8.
27,
11%
When 4-N-methyl-N-p-toluenesulfonylaminobutylic acid was converted into acid chloride by treatment with (CoCl), in CH,Cl, and then the chloride was treated with NEt, in THF at 0 r. the ketene dimer was obtained in 13% yield. Though the reaction was carried out upon heating, no cyclized product was obtained.
(Received in Japan 14 September 1995; revised 20 October 1995;
accepted
27 October
1995)