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Carbonylative [2+2] cycloaddition for the construction of β-lactam skeleton with palladium catalyst
00404039/93 $6.00 + .tXl PergRoss L&l
Teuahedmn Letters.Vol. 34, No. 41. PP. 6553-6556.1993 Printedin Great Britain
Carbonylative [2+2] Cycloaddition for the Construction P-Lactam Skeleton with Palladium Catalyst
Sigeru
TORII,*
Hiroshi
OKUMOTO,
A. K. M. Abdul
Masahiro
of
SADAKANE,
HAI, and Hideo TANAKA
Department of Applied Chemisvy, Faculty of Engineering. Okayama University, Tsushima-Naka. Okayama 700, JAPAN
Key
Abstract:
Words:
Carbonylation: Palladium Catalyst; [2+2] Cycloaddition; P-Lactam; Stereoselective
Palladium-catalyxd carbonylation of ally1 dicthyl phosphate in the presence of imines under CO pressure (30
Kgcm+*) gavehighlystereos&ctivclyeithercis- or rrans-3-vinyl-p-lactamcompounds,
dependingon the natumof the imincscmploycd,in high yields.
Crucial to the success of p-lactam synthesis is the requirement
way.’
of a simple and convenient preparative
Intensive efforts have been devoted to the development of methodologies, reagents, and synthetic
reactions.
Among the rest, the well documented reaction is the [2+2J cycloaddition of ketene and imine.t.2
However, the generation of the ketene invoking treatment of activated carboxylic acid derivatives such as acid chlorides with base sometimes deteriorates the potentiality.
We
noticed the diverse utility of acylmetal
complexes, especially palladium complexes produced by CO insertion, as the activated acyl compounds. Although a variety of collapse modes of acylmetal intermediates are demonstrated,3 an analogous reactivity between acylpalladium and acid chloride suggested us that the acylpalladium species are eligible for the precursors affording ketene or its equivalents. 4 Hence, palladium-catalyzed carbonylative [2+2] cycloaddition with imine has intrigued us due to the usefulness of the P-lactam antibiotics as well. We wish to describe the carbonylation of ally1 phosphate 1 in the presence of imine 4 leading to p-lactam 5. The phosphate 1 is known to undergo carbonylation via r-allylpalladium
2: 5 The intermediate 3 involves highly acidic protons a to
carbonyl, which would be abstracted with a weak base. 6 Thus formed ketene or carbanion can add to the imine 4 to give rise to the Cmembered ring 5.
The carbonylative approach with the advantages, no need of acid and
acid chloride and ready availability of 1, would complement the conventional ketene-imine cycloaddition.
@-l
O[(OEt), 0
1
Pd+
-
Pd+ -Of’(OEt)a
Pd+-Of’(OEt)z
0 2
3
6553
0
R2-N
4
5
6554
The general experimental equiv.), Pd2(dba)$HCl3
procedure is as follows.
1 (1.5
A solution of the imine 4, the ally1 phosphate
(2 mol%), PPh3 (8 mol%), and amine (2 equiv.) in THF was charged in a glass test
tube, which was then placed in a stainless pressure (30 Kgcm-2) at the temperature followed by flash column chromatography We have first examined
autoclave.
The reaction mixture was stirred for 5 h under CO
indicated in the footnotes of the following Tables.
A usual work up
on silica gel afforded the p-lactam 5.
some allylic derivatives
reported
to form r-allylpalladium
intermediates.
1 produced the g-lactam 5 in a good yield, whereas the
Interestingly,
only the reaction of the phosphate
carbonylation
of other allylic substrates such as acetate,5 carbonate,7 bromide,8 sulfone,g and phenyl etherto
gave 5 in very low yield or otherwise no desired material was isolated under these conditions. the proper conditions for these allylic compounds may realize the similar cycloaddition the base was very critical, imposing the use of a bulky tertiary amine.5 to be the best choice for the purpose. temperature
Table 1 summarizes
using the imines 4a-4c conjugated
high stereoselectivity
reactionP
Inspection of The kind of
c-Hex2NMe or i-PrzNEt was revealed
the results of the reaction performed
with carbonyl.
The cis-p-lactams
at room
Sa-Sc were. obtained
with
in spite of the susceptibility to the epimerization.l~ll Table 1. Formation of p-lactams using imines conjugated with carbonyl
Enny
Imine, 4
Product, 5 (%)
0
0 Ph
1
4a
PMP’
5a (58)
0
0 Ph
2
Ph 4b
Pr’
5b (50)
0
0
Ph 4o
Carried out at room temperature using c-Hex2NMe as a base. a) Obtained as a mixture of cis/trans isomers (5/l). In sharp contrast to the above results, the cycloaddition
using the imines 4d-4h, which are not conjugated
with carbonyl, resulted in the predominant formation of the runs-b-lactams reaction proceeded smoothly at 70 “C but was sluggish at room temperature.
5d-5h. As collected in Table 2, the The carbonylative
cycloaddition
with the stable imines 4d-4f led to the desired lactams 5d-5f in high yields (Entries l-3), while both 5g and 5h were obtained in lower yields due to the instability of 4g and 4h (Entries 4 and 5).
isomers
were not detected
temperature.
by 1H NMR analysis
The dependency
often observed.1
However,
(200 MHz) in each attempt
of the stereochemical the exclusive distribution
The corresponding
except
cis
5g even at room
outcome on the nature of the imine employed
has been
of either cis or trans isomer is worthy to emphasize.
Thus, the various p-lactams 5 bearing adequate substituents for further elaborations have been synthesized.
6555
Table 2. Cycloaddition using imines nonconjugated with carbonyl Imine, 4
Enny
Product, 5 (%) HH
1
4d
Pr’
Sd (72) H H
2
3
4e
Bn’
Bn’
49
4h3 Carried out at 70 ‘C using i-PraNEt. a) The imine was not pure due to the instability. b) Obtained as a mixture of trans/cis isomers (X/l).
The exact reaction path remains unexplained.
formation6 of ketene 6, which is probably complexed
Assumable paths are depicted below, in which a direct
with Pd,3 from the acylpalladium
3 would be one entry.
’ acid chlorides do. Two metallacycles ds which may stem from the ketene-palladium complex and imine.
Acyl phosphate 78 may serve as an activated acyl derivative,‘2 9 am also conceivable intermediates,
Pd+ 3
8 and
-
-OP(OEt)2 ;
Several transition metal assisted carbonylations forming g-lactam structure have been exploited in an intramolecular stoichiometric
sense.]3
Hegedus reported g-lactam
carbene complex. 14
The catalytic
synthesis by photolytic
carbonylation
generation
of the ally1 phosphate
of ketene with
1 provides a new
candidate for ketene or its equivalents and a convenient way to the p-lactam framework.
wide range of 3-alkenyl-g-lactams
with stereodefined
the appropriate choice of the reaction partners. synthesize useful antibiotics are under way.
The construction of a array of the proper substituents should be feasible through
Now, further cxpcrimcnts
to understand the reaction path and to
6556
SC-NMR Laboratory of Okayama University is appreciated for obtaining high resolution NMR spectra. REFERENCES AND NOTES 1.
Thomas, R. C. in Recent Progress in the Chemical Synthesis of’Antibiotics; Lukacs, G.; Ohno. M. Eds.;
2.
Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon Press: Oxford, 1990. chap. 7.
3.
Tsuji, J. Organic Synthesis with Palladium Compounds; Springer Verlag: Berlin, 1980. Heck, R. F.
Springer Verlag: Berlin, 1990, 534-564. Palomo, C. ibid., 565-612.
Palladium Reagents in Organic Syntheses; Academic Press: London, 1985.
4.
Miyashita, A.; Kawashima, T.; Kaji, S.; Nomura, K.; Nohira, H. Tetrahedron L&t. 1991,32,781-784. Iwasaki, M.; Kobayashi, Y.; Li, J.; Matsuzaka, H.; Ishii, Y.; Hidai, M. J. Org. Chem. 1991.56.
1922-
1927. Wouters, J. M. A.; Avis, M. W.; Elsevier, C. J.; Kyriakidis, C. E.; Stam, C. H. Organometalfics 1990, 9, 2203-2205. Huser, M.; Youinou, M.; Osborn, J. A. Angew. Chem. Int. Ed. Engl. 1989,28, 1386-1388. Miyashita, A.; Nomura, K.; Kaji, S.; Nohira, H. Chem. Lett. 1989, 1983-1986. Miyashita,
A.; Kihara, T.; Nomura, K.; Nohira, H. Chem. Lett. 1986, 1607-1610. Hommeltoft, S. I.; Baird, M. C. Organometallics 1986.5,
190-195. Bodnar, T. W.; Crawford, E. J.; Cutler, A. R. Organometallics
1986,5, 947-950. Miyashita, A.; Shitora, H.; Nohira, H. Organometallics 1985,4, 5.
Murahashi, S.; Imada, Y.; Taniguchi, Y.; Higashiura, S. -1. Org. Chem. 1993,58, Tetrahedron Lett. 1988.29,
1463-1464.
1538-1545. Idem,
4945-4948.
6.
Guangzhong, W.; Shimoyama, 1.; Negishi, E. J. Org. Chem. 1991,56,
7.
Tsuji, J.; Sato, K.; Okumoto, H. J. Org. Chem. lY84,49,
8.
Tsuji, J.; Kiji, J.; Imamura, S.; Morikawa, M. J. Am. Chem. Sot. lY64.86,
6506-6507.
1341-1344. 4350-4353. Dent, W. T.;
Long, R.; Whitfield, G. H. J. Chem. Sot. lY64, 1588-1594. Merrifield, J. H.; Godschalx, J. P.; Stille, J. K. Organometallics 1984,3, 9.
1108-I 112.
Trost, B. M.; Schmuff, N. R.; Miller, M. J. J. Am. Chem. Sot. 1980,102,
5979-5981.
10. Tsuji, J.; Kobayashi, Y.; Kataoka, H.; Takahashi, T. Tetrahedron Lett. 1980,21,
1475-1478.
11. Tschaen, D. M.; Fuentes, L. M.; Lynch, J. E.; Laswell, W. L.; Volante, R. P.; Shinkai, I. Tetrahedron Lett. 1988,29,
2779-2782.
Manhas, M. S.; Ghosh, M.; Bose, A. K. J. Org. Chem. 1990,55,
575-
580. 12.
For a similar intermediate in 12+21cycloaddition, see; Arrieta, A.; Cossio, F. P.; Palomo, C. Tetrahedron
13.
Torii, S.; Okumoto, H.; Sadakane, M.; Xu, L. Chem. Lett. 1991, 1673-1676. Mandai, T.; Ryoden, K.;
1985.41,
1703-1712.
Kawada, M.; Tsuji, J. Tetrahedron Lett. 19Y1.32, 7683-7686. Matsuda, I.; Sakakibara, J.; Nagashima, H. Tetrahedron Lett. 1991,32,
7431-7434. Spears, G. W.; Nakanishi, K.; Ohfune, Y. Synlett 1991,
91-92. Calet, S.; Urso, F.; Alper, H. J. Am. Chem. Sot. 1989, Ill, Tetrahedron Lett. lY87.28, 1985,41,
931-934. Alper, H.; Hamel, N.
3237-3240. Mori, M.; Chiba, K.; Okita, M.; Kayo. I.; Ban, Y. Tetrahedron
375-385. Hodgson, S. T.; Hollinshead, D. M.; Ley, S. V. Tetrahedron
1985,42,
5871-
5878. Wong, P. K.; Madhavarao, M.; Marten, D. F.; Rosenblum, M. J. Am. Chem. Sot. 1977,99, 2823-2824. Aida, T.; Legault, R.; Dugat, D.; Durst, T. Tetrahedron Lett. 1979, 4YY3-4994. 14.
Narukawa, Y.; Juneau, K. N.; Snustad, D.; Miller, D. B.; Hegedus, L. S. J. Org. Chem. 1992.57, 5453-5462. and references cited therein.
(Received in Japan 9 April 1993; accepted 4 June 1993)
Teuahedmn Letters.Vol. 34, No. 41. PP. 6553-6556.1993 Printedin Great Britain
Carbonylative [2+2] Cycloaddition for the Construction P-Lactam Skeleton with Palladium Catalyst
Sigeru
TORII,*
Hiroshi
OKUMOTO,
A. K. M. Abdul
Masahiro
of
SADAKANE,
HAI, and Hideo TANAKA
Department of Applied Chemisvy, Faculty of Engineering. Okayama University, Tsushima-Naka. Okayama 700, JAPAN
Key
Abstract:
Words:
Carbonylation: Palladium Catalyst; [2+2] Cycloaddition; P-Lactam; Stereoselective
Palladium-catalyxd carbonylation of ally1 dicthyl phosphate in the presence of imines under CO pressure (30
Kgcm+*) gavehighlystereos&ctivclyeithercis- or rrans-3-vinyl-p-lactamcompounds,
dependingon the natumof the imincscmploycd,in high yields.
Crucial to the success of p-lactam synthesis is the requirement
way.’
of a simple and convenient preparative
Intensive efforts have been devoted to the development of methodologies, reagents, and synthetic
reactions.
Among the rest, the well documented reaction is the [2+2J cycloaddition of ketene and imine.t.2
However, the generation of the ketene invoking treatment of activated carboxylic acid derivatives such as acid chlorides with base sometimes deteriorates the potentiality.
We
noticed the diverse utility of acylmetal
complexes, especially palladium complexes produced by CO insertion, as the activated acyl compounds. Although a variety of collapse modes of acylmetal intermediates are demonstrated,3 an analogous reactivity between acylpalladium and acid chloride suggested us that the acylpalladium species are eligible for the precursors affording ketene or its equivalents. 4 Hence, palladium-catalyzed carbonylative [2+2] cycloaddition with imine has intrigued us due to the usefulness of the P-lactam antibiotics as well. We wish to describe the carbonylation of ally1 phosphate 1 in the presence of imine 4 leading to p-lactam 5. The phosphate 1 is known to undergo carbonylation via r-allylpalladium
2: 5 The intermediate 3 involves highly acidic protons a to
carbonyl, which would be abstracted with a weak base. 6 Thus formed ketene or carbanion can add to the imine 4 to give rise to the Cmembered ring 5.
The carbonylative approach with the advantages, no need of acid and
acid chloride and ready availability of 1, would complement the conventional ketene-imine cycloaddition.
@-l
O[(OEt), 0
1
Pd+
-
Pd+ -Of’(OEt)a
Pd+-Of’(OEt)z
0 2
3
6553
0
R2-N
4
5
6554
The general experimental equiv.), Pd2(dba)$HCl3
procedure is as follows.
1 (1.5
A solution of the imine 4, the ally1 phosphate
(2 mol%), PPh3 (8 mol%), and amine (2 equiv.) in THF was charged in a glass test
tube, which was then placed in a stainless pressure (30 Kgcm-2) at the temperature followed by flash column chromatography We have first examined
autoclave.
The reaction mixture was stirred for 5 h under CO
indicated in the footnotes of the following Tables.
A usual work up
on silica gel afforded the p-lactam 5.
some allylic derivatives
reported
to form r-allylpalladium
intermediates.
1 produced the g-lactam 5 in a good yield, whereas the
Interestingly,
only the reaction of the phosphate
carbonylation
of other allylic substrates such as acetate,5 carbonate,7 bromide,8 sulfone,g and phenyl etherto
gave 5 in very low yield or otherwise no desired material was isolated under these conditions. the proper conditions for these allylic compounds may realize the similar cycloaddition the base was very critical, imposing the use of a bulky tertiary amine.5 to be the best choice for the purpose. temperature
Table 1 summarizes
using the imines 4a-4c conjugated
high stereoselectivity
reactionP
Inspection of The kind of
c-Hex2NMe or i-PrzNEt was revealed
the results of the reaction performed
with carbonyl.
The cis-p-lactams
at room
Sa-Sc were. obtained
with
in spite of the susceptibility to the epimerization.l~ll Table 1. Formation of p-lactams using imines conjugated with carbonyl
Enny
Imine, 4
Product, 5 (%)
0
0 Ph
1
4a
PMP’
5a (58)
0
0 Ph
2
Ph 4b
Pr’
5b (50)
0
0
Ph 4o
Carried out at room temperature using c-Hex2NMe as a base. a) Obtained as a mixture of cis/trans isomers (5/l). In sharp contrast to the above results, the cycloaddition
using the imines 4d-4h, which are not conjugated
with carbonyl, resulted in the predominant formation of the runs-b-lactams reaction proceeded smoothly at 70 “C but was sluggish at room temperature.
5d-5h. As collected in Table 2, the The carbonylative
cycloaddition
with the stable imines 4d-4f led to the desired lactams 5d-5f in high yields (Entries l-3), while both 5g and 5h were obtained in lower yields due to the instability of 4g and 4h (Entries 4 and 5).
isomers
were not detected
temperature.
by 1H NMR analysis
The dependency
often observed.1
However,
(200 MHz) in each attempt
of the stereochemical the exclusive distribution
The corresponding
except
cis
5g even at room
outcome on the nature of the imine employed
has been
of either cis or trans isomer is worthy to emphasize.
Thus, the various p-lactams 5 bearing adequate substituents for further elaborations have been synthesized.
6555
Table 2. Cycloaddition using imines nonconjugated with carbonyl Imine, 4
Enny
Product, 5 (%) HH
1
4d
Pr’
Sd (72) H H
2
3
4e
Bn’
Bn’
49
4h3 Carried out at 70 ‘C using i-PraNEt. a) The imine was not pure due to the instability. b) Obtained as a mixture of trans/cis isomers (X/l).
The exact reaction path remains unexplained.
formation6 of ketene 6, which is probably complexed
Assumable paths are depicted below, in which a direct
with Pd,3 from the acylpalladium
3 would be one entry.
’ acid chlorides do. Two metallacycles ds which may stem from the ketene-palladium complex and imine.
Acyl phosphate 78 may serve as an activated acyl derivative,‘2 9 am also conceivable intermediates,
Pd+ 3
8 and
-
-OP(OEt)2 ;
Several transition metal assisted carbonylations forming g-lactam structure have been exploited in an intramolecular stoichiometric
sense.]3
Hegedus reported g-lactam
carbene complex. 14
The catalytic
synthesis by photolytic
carbonylation
generation
of the ally1 phosphate
of ketene with
1 provides a new
candidate for ketene or its equivalents and a convenient way to the p-lactam framework.
wide range of 3-alkenyl-g-lactams
with stereodefined
the appropriate choice of the reaction partners. synthesize useful antibiotics are under way.
The construction of a array of the proper substituents should be feasible through
Now, further cxpcrimcnts
to understand the reaction path and to
6556
SC-NMR Laboratory of Okayama University is appreciated for obtaining high resolution NMR spectra. REFERENCES AND NOTES 1.
Thomas, R. C. in Recent Progress in the Chemical Synthesis of’Antibiotics; Lukacs, G.; Ohno. M. Eds.;
2.
Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon Press: Oxford, 1990. chap. 7.
3.
Tsuji, J. Organic Synthesis with Palladium Compounds; Springer Verlag: Berlin, 1980. Heck, R. F.
Springer Verlag: Berlin, 1990, 534-564. Palomo, C. ibid., 565-612.
Palladium Reagents in Organic Syntheses; Academic Press: London, 1985.
4.
Miyashita, A.; Kawashima, T.; Kaji, S.; Nomura, K.; Nohira, H. Tetrahedron L&t. 1991,32,781-784. Iwasaki, M.; Kobayashi, Y.; Li, J.; Matsuzaka, H.; Ishii, Y.; Hidai, M. J. Org. Chem. 1991.56.
1922-
1927. Wouters, J. M. A.; Avis, M. W.; Elsevier, C. J.; Kyriakidis, C. E.; Stam, C. H. Organometalfics 1990, 9, 2203-2205. Huser, M.; Youinou, M.; Osborn, J. A. Angew. Chem. Int. Ed. Engl. 1989,28, 1386-1388. Miyashita, A.; Nomura, K.; Kaji, S.; Nohira, H. Chem. Lett. 1989, 1983-1986. Miyashita,
A.; Kihara, T.; Nomura, K.; Nohira, H. Chem. Lett. 1986, 1607-1610. Hommeltoft, S. I.; Baird, M. C. Organometallics 1986.5,
190-195. Bodnar, T. W.; Crawford, E. J.; Cutler, A. R. Organometallics
1986,5, 947-950. Miyashita, A.; Shitora, H.; Nohira, H. Organometallics 1985,4, 5.
Murahashi, S.; Imada, Y.; Taniguchi, Y.; Higashiura, S. -1. Org. Chem. 1993,58, Tetrahedron Lett. 1988.29,
1463-1464.
1538-1545. Idem,
4945-4948.
6.
Guangzhong, W.; Shimoyama, 1.; Negishi, E. J. Org. Chem. 1991,56,
7.
Tsuji, J.; Sato, K.; Okumoto, H. J. Org. Chem. lY84,49,
8.
Tsuji, J.; Kiji, J.; Imamura, S.; Morikawa, M. J. Am. Chem. Sot. lY64.86,
6506-6507.
1341-1344. 4350-4353. Dent, W. T.;
Long, R.; Whitfield, G. H. J. Chem. Sot. lY64, 1588-1594. Merrifield, J. H.; Godschalx, J. P.; Stille, J. K. Organometallics 1984,3, 9.
1108-I 112.
Trost, B. M.; Schmuff, N. R.; Miller, M. J. J. Am. Chem. Sot. 1980,102,
5979-5981.
10. Tsuji, J.; Kobayashi, Y.; Kataoka, H.; Takahashi, T. Tetrahedron Lett. 1980,21,
1475-1478.
11. Tschaen, D. M.; Fuentes, L. M.; Lynch, J. E.; Laswell, W. L.; Volante, R. P.; Shinkai, I. Tetrahedron Lett. 1988,29,
2779-2782.
Manhas, M. S.; Ghosh, M.; Bose, A. K. J. Org. Chem. 1990,55,
575-
580. 12.
For a similar intermediate in 12+21cycloaddition, see; Arrieta, A.; Cossio, F. P.; Palomo, C. Tetrahedron
13.
Torii, S.; Okumoto, H.; Sadakane, M.; Xu, L. Chem. Lett. 1991, 1673-1676. Mandai, T.; Ryoden, K.;
1985.41,
1703-1712.
Kawada, M.; Tsuji, J. Tetrahedron Lett. 19Y1.32, 7683-7686. Matsuda, I.; Sakakibara, J.; Nagashima, H. Tetrahedron Lett. 1991,32,
7431-7434. Spears, G. W.; Nakanishi, K.; Ohfune, Y. Synlett 1991,
91-92. Calet, S.; Urso, F.; Alper, H. J. Am. Chem. Sot. 1989, Ill, Tetrahedron Lett. lY87.28, 1985,41,
931-934. Alper, H.; Hamel, N.
3237-3240. Mori, M.; Chiba, K.; Okita, M.; Kayo. I.; Ban, Y. Tetrahedron
375-385. Hodgson, S. T.; Hollinshead, D. M.; Ley, S. V. Tetrahedron
1985,42,
5871-
5878. Wong, P. K.; Madhavarao, M.; Marten, D. F.; Rosenblum, M. J. Am. Chem. Sot. 1977,99, 2823-2824. Aida, T.; Legault, R.; Dugat, D.; Durst, T. Tetrahedron Lett. 1979, 4YY3-4994. 14.
Narukawa, Y.; Juneau, K. N.; Snustad, D.; Miller, D. B.; Hegedus, L. S. J. Org. Chem. 1992.57, 5453-5462. and references cited therein.
(Received in Japan 9 April 1993; accepted 4 June 1993)