Studies on nonconventionally fused bicyclic β-lactams

Journal of Organic Chemistry

Volumn 63, Issue 24, 1998, Pages 8898-8917

  Ren, Xiao Feng ^a   Konaklieva, Monika I ^a   Shi, Hongchang ^b   Dickey, Sonja ^c   Lim, Daniel V ^c   Gonzalez, Javier ^d   Turos, Edward ^c  

^a UNIVERSITY AT BUFFALO   (United States)

^b TSINGHUA UNIVERSITY   (China)

^c UNIVERSITY OF SOUTH FLORIDA   (United States)

^d UNIVERSITY OF OVIEDO   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

BETA LACTAM ANTIBIOTIC; PALLADIUM; PENAM DERIVATIVE; PENEM DERIVATIVE;

ARTICLE; CATALYSIS; CHEMICAL ANALYSIS; CHEMICAL STRUCTURE; CYCLIZATION; DRUG STRUCTURE; THERMOSTABILITY;

EID: 0031735116     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9811219     Document Type: Article

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75. [2 + 2]-cycloadditions of α-arylthioacetyl chlorides with imines have been reported previously. (a) Palomo, C.; Cossio, F. P.; Odiozola, J. M.; Oiarbide, M.; Ontoria, J. M. Tetrahedron Lett. 1989, 30, 4577. (b) Palomo, C.; Cossio, F. P.; Odiozola, J. M.; Oiarbide, M.; Ontoria, J. M. J. Org. Chem. 1991, 56, 4418. (c) Ishida, M.; Minami, T.; Agawa, T. J. Org. Chem. 1979, 44, 2069.
76. [2 + 2]-cycloadditions of α-arylthioacetyl chlorides with imines have been reported previously. (a) Palomo, C.; Cossio, F. P.; Odiozola, J. M.; Oiarbide, M.; Ontoria, J. M. Tetrahedron Lett. 1989, 30, 4577. (b) Palomo, C.; Cossio, F. P.; Odiozola, J. M.; Oiarbide, M.; Ontoria, J. M. J. Org. Chem. 1991, 56, 4418. (c) Ishida, M.; Minami, T.; Agawa, T. J. Org. Chem. 1979, 44, 2069.
77. This halocyclization procedure is somewhat reminiscent of the classical Morin isomerization of penicillin sulfoxides to cephams, a process thought to occur via intramolecular addition of an electrophilic sulfur group to an olefin. (Morin, R. B.; Jackson, B. G.; Mueller, R. A.; Lavagnino, E. R.; Scanlon, W. B.; Andrews, S. L. J. Am. Chem. Soc. 1963, 85, 1896.) For discussions and references, see: (a) Cooper, R. D. G.; Hatfield, L. D.; Spry, D. O. Acc. Chem. Res. 1973, 6, 32. (b) Chemistry and Biology of β-Lactam Antibiotics; Morin, R. B., Gorman, M., Eds.; Academic Press: New York, 1982; Vol. I. For related methodology involving an intramolecular sulfenylation of an allene, see: Farina, V.; Kant, J. Tetrahedron Lett. 1992, 33, 3559.
78. This halocyclization procedure is somewhat reminiscent of the classical Morin isomerization of penicillin sulfoxides to cephams, a process thought to occur via intramolecular addition of an electrophilic sulfur group to an olefin. (Morin, R. B.; Jackson, B. G.; Mueller, R. A.; Lavagnino, E. R.; Scanlon, W. B.; Andrews, S. L. J. Am. Chem. Soc. 1963, 85, 1896.) For discussions and references, see: (a) Cooper, R. D. G.; Hatfield, L. D.; Spry, D. O. Acc. Chem. Res. 1973, 6, 32. (b) Chemistry and Biology of β-Lactam Antibiotics; Morin, R. B., Gorman, M., Eds.; Academic Press: New York, 1982; Vol. I. For related methodology involving an intramolecular sulfenylation of an allene, see: Farina, V.; Kant, J. Tetrahedron Lett. 1992, 33, 3559.
79. This halocyclization procedure is somewhat reminiscent of the classical Morin isomerization of penicillin sulfoxides to cephams, a process thought to occur via intramolecular addition of an electrophilic sulfur group to an olefin. (Morin, R. B.; Jackson, B. G.; Mueller, R. A.; Lavagnino, E. R.; Scanlon, W. B.; Andrews, S. L. J. Am. Chem. Soc. 1963, 85, 1896.) For discussions and references, see: (a) Cooper, R. D. G.; Hatfield, L. D.; Spry, D. O. Acc. Chem. Res. 1973, 6, 32. (b) Chemistry and Biology of β-Lactam Antibiotics; Morin, R. B., Gorman, M., Eds.; Academic Press: New York, 1982; Vol. I. For related methodology involving an intramolecular sulfenylation of an allene, see: Farina, V.; Kant, J. Tetrahedron Lett. 1992, 33, 3559.
80. This halocyclization procedure is somewhat reminiscent of the classical Morin isomerization of penicillin sulfoxides to cephams, a process thought to occur via intramolecular addition of an electrophilic sulfur group to an olefin. (Morin, R. B.; Jackson, B. G.; Mueller, R. A.; Lavagnino, E. R.; Scanlon, W. B.; Andrews, S. L. J. Am. Chem. Soc. 1963, 85, 1896.) For discussions and references, see: (a) Cooper, R. D. G.; Hatfield, L. D.; Spry, D. O. Acc. Chem. Res. 1973, 6, 32. (b) Chemistry and Biology of β-Lactam Antibiotics; Morin, R. B., Gorman, M., Eds.; Academic Press: New York, 1982; Vol. I. For related methodology involving an intramolecular sulfenylation of an allene, see: Farina, V.; Kant, J. Tetrahedron Lett. 1992, 33, 3559.
81. This acid chloride can be easily prepared from the commercially available carboxylic acid by refluxing in thionyl chloride.
82. For examples and discussions on the synthesis of α-alkoxy- and α-amino-substituted β-lactams, refer to ref 7b, Chapter 6, pp 295-368.
83. We speculate that this isomeric material may be a [4 + 2]-cycloadduct that forms between the crotonimine and ketene, although no attempt was made to confirm this structure.
84. Preliminary accounts of this research have been communicated in the following articles: (a) Ren, X.-F.; Turos, E. J. Org. Chem. 1994, 59, 5858. (b) Ren, X.-F.; Konaklieva, M. I.; Turos, E. J. Org. Chem. 1995, 60, 4980. (c) Konaklieva, I.; Shi, H.; Turos, E. Tetrahedron Lett. 1997, 38, 8647. Also, refer to ref 28b.
85. Preliminary accounts of this research have been communicated in the following articles: (a) Ren, X.-F.; Turos, E. J. Org. Chem. 1994, 59, 5858. (b) Ren, X.-F.; Konaklieva, M. I.; Turos, E. J. Org. Chem. 1995, 60, 4980. (c) Konaklieva, I.; Shi, H.; Turos, E. Tetrahedron Lett. 1997, 38, 8647. Also, refer to ref 28b.
86. Preliminary accounts of this research have been communicated in the following articles: (a) Ren, X.-F.; Turos, E. J. Org. Chem. 1994, 59, 5858. (b) Ren, X.-F.; Konaklieva, M. I.; Turos, E. J. Org. Chem. 1995, 60, 4980. (c) Konaklieva, I.; Shi, H.; Turos, E. Tetrahedron Lett. 1997, 38, 8647. Also, refer to ref 28b.
87. For instance, 7α-methoxylation of the cephalosporin ring system markedly enhances β-lactamase resistance. (a) Strominger, J. L.; Tipper, D. J. Am. J. Med. 1965, 39, 707. (b) Cama, L. D.; Leanza, W. J.; Beattie, T. R.; Christensen, B. G. J. Am. Chem. Soc. 1972, 94, 1408. (c) Stapley, E. O.; Birnbaum, J.; Miller, A. K.; Wallick, H.; Hendlin, D.; Woodruff, H. B. Rev. Inf. Dis. 1979, 1, 73 and references therein. (d) Nagarajan, R.; Boeck, L. D.; Gorman, M.; Hamill, R. L.; Higgens, C. E.; Hoehn, M. M.; Stark, W. M.; Whitney, J. G. J. Am. Chem. Soc. 1971, 93, 2308. However, heterosubstitution on the penicillin core generally diminishes antibiotic activity (Bentley, P. H.; Clayton, J. P. In Recent Advances in the Chemistry of β-Lactam Antibiotics; Elks, J., Ed.; Special Publication No. 28, The Chemical Society: London, 1977; pp 68-72), although the penicillin derivative temocillin seems to be an exception (Slocombe, B.; Basker, M. J.; Bentley, P. H.; Clayton, J. P.; Cole, M.; Comber, K. R.; Dixon, R. A.; Edmondson, R. A.; Jackson, D.; Merrikin, D. J.; Sutherland, R Antimicrob. Agents Chemother. 1981, 20, 38).
88. For instance, 7α-methoxylation of the cephalosporin ring system markedly enhances β-lactamase resistance. (a) Strominger, J. L.; Tipper, D. J. Am. J. Med. 1965, 39, 707. (b) Cama, L. D.; Leanza, W. J.; Beattie, T. R.; Christensen, B. G. J. Am. Chem. Soc. 1972, 94, 1408. (c) Stapley, E. O.; Birnbaum, J.; Miller, A. K.; Wallick, H.; Hendlin, D.; Woodruff, H. B. Rev. Inf. Dis. 1979, 1, 73 and references therein. (d) Nagarajan, R.; Boeck, L. D.; Gorman, M.; Hamill, R. L.; Higgens, C. E.; Hoehn, M. M.; Stark, W. M.; Whitney, J. G. J. Am. Chem. Soc. 1971, 93, 2308. However, heterosubstitution on the penicillin core generally diminishes antibiotic activity (Bentley, P. H.; Clayton, J. P. In Recent Advances in the Chemistry of β-Lactam Antibiotics; Elks, J., Ed.; Special Publication No. 28, The Chemical Society: London, 1977; pp 68-72), although the penicillin derivative temocillin seems to be an exception (Slocombe, B.; Basker, M. J.; Bentley, P. H.; Clayton, J. P.; Cole, M.; Comber, K. R.; Dixon, R. A.; Edmondson, R. A.; Jackson, D.; Merrikin, D. J.; Sutherland, R Antimicrob. Agents Chemother. 1981, 20, 38).
89. For instance, 7α-methoxylation of the cephalosporin ring system markedly enhances β-lactamase resistance. (a) Strominger, J. L.; Tipper, D. J. Am. J. Med. 1965, 39, 707. (b) Cama, L. D.; Leanza, W. J.; Beattie, T. R.; Christensen, B. G. J. Am. Chem. Soc. 1972, 94, 1408. (c) Stapley, E. O.; Birnbaum, J.; Miller, A. K.; Wallick, H.; Hendlin, D.; Woodruff, H. B. Rev. Inf. Dis. 1979, 1, 73 and references therein. (d) Nagarajan, R.; Boeck, L. D.; Gorman, M.; Hamill, R. L.; Higgens, C. E.; Hoehn, M. M.; Stark, W. M.; Whitney, J. G. J. Am. Chem. Soc. 1971, 93, 2308. However, heterosubstitution on the penicillin core generally diminishes antibiotic activity (Bentley, P. H.; Clayton, J. P. In Recent Advances in the Chemistry of β-Lactam Antibiotics; Elks, J., Ed.; Special Publication No. 28, The Chemical Society: London, 1977; pp 68-72), although the penicillin derivative temocillin seems to be an exception (Slocombe, B.; Basker, M. J.; Bentley, P. H.; Clayton, J. P.; Cole, M.; Comber, K. R.; Dixon, R. A.; Edmondson, R. A.; Jackson, D.; Merrikin, D. J.; Sutherland, R Antimicrob. Agents Chemother. 1981, 20, 38).
90. For instance, 7α-methoxylation of the cephalosporin ring system markedly enhances β-lactamase resistance. (a) Strominger, J. L.; Tipper, D. J. Am. J. Med. 1965, 39, 707. (b) Cama, L. D.; Leanza, W. J.; Beattie, T. R.; Christensen, B. G. J. Am. Chem. Soc. 1972, 94, 1408. (c) Stapley, E. O.; Birnbaum, J.; Miller, A. K.; Wallick, H.; Hendlin, D.; Woodruff, H. B. Rev. Inf. Dis. 1979, 1, 73 and references therein. (d) Nagarajan, R.; Boeck, L. D.; Gorman, M.; Hamill, R. L.; Higgens, C. E.; Hoehn, M. M.; Stark, W. M.; Whitney, J. G. J. Am. Chem. Soc. 1971, 93, 2308. However, heterosubstitution on the penicillin core generally diminishes antibiotic activity (Bentley, P. H.; Clayton, J. P. In Recent Advances in the Chemistry of β-Lactam Antibiotics; Elks, J., Ed.; Special Publication No. 28, The Chemical Society: London, 1977; pp 68-72), although the penicillin derivative temocillin seems to be an exception (Slocombe, B.; Basker, M. J.; Bentley, P. H.; Clayton, J. P.; Cole, M.; Comber, K. R.; Dixon, R. A.; Edmondson, R. A.; Jackson, D.; Merrikin, D. J.; Sutherland, R Antimicrob. Agents Chemother. 1981, 20, 38).
91. For instance, 7α-methoxylation of the cephalosporin ring system markedly enhances β-lactamase resistance. (a) Strominger, J. L.; Tipper, D. J. Am. J. Med. 1965, 39, 707. (b) Cama, L. D.; Leanza, W. J.; Beattie, T. R.; Christensen, B. G. J. Am. Chem. Soc. 1972, 94, 1408. (c) Stapley, E. O.; Birnbaum, J.; Miller, A. K.; Wallick, H.; Hendlin, D.; Woodruff, H. B. Rev. Inf. Dis. 1979, 1, 73 and references therein. (d) Nagarajan, R.; Boeck, L. D.; Gorman, M.; Hamill, R. L.; Higgens, C. E.; Hoehn, M. M.; Stark, W. M.; Whitney, J. G. J. Am. Chem. Soc. 1971, 93, 2308. However, heterosubstitution on the penicillin core generally diminishes antibiotic activity (Bentley, P. H.; Clayton, J. P. In Recent Advances in the Chemistry of β-Lactam Antibiotics; Elks, J., Ed.; Special Publication No. 28, The Chemical Society: London, 1977; pp 68-72), although the penicillin derivative temocillin seems to be an exception (Slocombe, B.; Basker, M. J.; Bentley, P. H.; Clayton, J. P.; Cole, M.; Comber, K. R.; Dixon, R. A.; Edmondson, R. A.; Jackson, D.; Merrikin, D. J.; Sutherland, R Antimicrob. Agents Chemother. 1981, 20, 38).
92. For instance, 7α-methoxylation of the cephalosporin ring system markedly enhances β-lactamase resistance. (a) Strominger, J. L.; Tipper, D. J. Am. J. Med. 1965, 39, 707. (b) Cama, L. D.; Leanza, W. J.; Beattie, T. R.; Christensen, B. G. J. Am. Chem. Soc. 1972, 94, 1408. (c) Stapley, E. O.; Birnbaum, J.; Miller, A. K.; Wallick, H.; Hendlin, D.; Woodruff, H. B. Rev. Inf. Dis. 1979, 1, 73 and references therein. (d) Nagarajan, R.; Boeck, L. D.; Gorman, M.; Hamill, R. L.; Higgens, C. E.; Hoehn, M. M.; Stark, W. M.; Whitney, J. G. J. Am. Chem. Soc. 1971, 93, 2308. However, heterosubstitution on the penicillin core generally diminishes antibiotic activity (Bentley, P. H.; Clayton, J. P. In Recent Advances in the Chemistry of β-Lactam Antibiotics; Elks, J., Ed.; Special Publication No. 28, The Chemical Society: London, 1977; pp 68-72), although the penicillin derivative temocillin seems to be an exception (Slocombe, B.; Basker, M. J.; Bentley, P. H.; Clayton, J. P.; Cole, M.; Comber, K. R.; Dixon, R. A.; Edmondson, R. A.; Jackson, D.; Merrikin, D. J.; Sutherland, R Antimicrob. Agents Chemother. 1981, 20, 38).
93. Sharma, S. D.; Mehra, U.; Khurana, J. P. S.; Pandhi, S. B. Synthesis 1987, 990.
94. The synthesis of 3-bis(ethylthio)azetidinones has been reported previously. Cossio, F. P.; Ganboa, I.; Garcia, J. M.; Lecea, B.; Palomo, C. Tetrahedron Lett. 1987, 28, 1945. Also see: Abramski, W.; Belzecki, C.; Chielewski, M. Bull. Pol. Acad. Sci. Chem. 1985, 33, 451.
95. The synthesis of 3-bis(ethylthio)azetidinones has been reported previously. Cossio, F. P.; Ganboa, I.; Garcia, J. M.; Lecea, B.; Palomo, C. Tetrahedron Lett. 1987, 28, 1945. Also see: Abramski, W.; Belzecki, C.; Chielewski, M. Bull. Pol. Acad. Sci. Chem. 1985, 33, 451.
96. In the bromination reaction of 33, a small amount of the proto derivative (shown below) can also be obtained, presumably from HBr-promoted ring closure. equation presented
97. (a) Slusarchyk, W. A.; Dejneka, T.; Gordon, E. M.; Weaver, E. R.; Koster, W. H. Heterocycles 1984, 21, 191.
98. (b) Cimarusti, C. M.; Sykes, R. B. Med. Res. Rev. 1984, 4, 1.
99. Cis-disubstituted β-lactams characteristically show a vicinal coupling constant of 4.8-6.0 Hz, while for trans-disubstituted β-lactams this value is typically only 1-3 Hz.
100. Kronenthal, D. R.; Han, C. Y.; Taylor, M. K. J. Org. Chem. 1982, 47, 2765.
101. Shah, N. V.; Cama, L. D. Heterocycles 1987, 25, 221.
102. Raban, M. Tetrahedron 1984, 40, 3345.
103. (a) Woulfe, S. R.; Miller, M. J. J. Med. Chem. 1985, 28, 1447.
104. (b) Woulfe, S. R.; Miller, M. J. J. Org. Chem. 1986, 51, 3133.
105. 2R group. equation presented
106. The proton NMR spectra of the adducts 43 and 44 from bromination of trans-40 and trans-41 shows the retention of the azetidinyl S-Me groups (appearing as separate singlets for the two diastereomers).
107. For more detailed discussions on stereoelectronic requirements in sulfur halocyclizations, see the papers cited in ref 28 as well as the following article on related cyclization chemistry. Ren, X.-F.; Konaklieva, M. I.; Turos, E.; Krajkowski, L. M.; Lake, C. H.; Janik, T. S.; Churchill, M. R. J. Org. Chem. 1995, 60, 6484.
108. (a) Chérest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 9, 2199.
109. (b) Anh, N. T.; Eisenstein, O. Nouv. J. Chem. 1977, 1, 61.
110. -1, respectively. (See: Demarco, P. V.; Nagarajan, R. In Cephalosporins and Penicillins: Chemistry and Biology; Flynn, E. H., Ed., Academic Press: New York, 1972; pp 315-320). Penicillin sulfones lack antibiotic activity but show β-lactamase inhibition. (For insight into their mechanism of action and lead references, see: Fink, A. L.; Ellerby, L. M.; Bassett, P. M. J. Am. Chem. Soc. 1989, 111, 6871).
111. -1, respectively. (See: Demarco, P. V.; Nagarajan, R. In Cephalosporins and Penicillins: Chemistry and Biology; Flynn, E. H., Ed., Academic Press: New York, 1972; pp 315-320). Penicillin sulfones lack antibiotic activity but show β-lactamase inhibition. (For insight into their mechanism of action and lead references, see: Fink, A. L.; Ellerby, L. M.; Bassett, P. M. J. Am. Chem. Soc. 1989, 111, 6871).
112. (a) Cooper, R. D. G.; DeMarco, P. V.; Cheng, J. C.; Jones, N. D. J. Am. Chem. Soc. 1969, 91, 1408.
113. (b) Cooper, R. D. G.; DeMarco, P. V.; Spry, D. O. J. Am. Chem. Soc. 1969, 91, 1528.
114. (a) Imtiaz, U.; Billings, E.; Knox, J. R.; Manavathu, E. K.; Lerner, S. A.; Mobashery, S. J. Am. Chem. Soc. 1993, 115, 4435.
115. (b) Knox, J. R.; Moews, P. C. J. Mol. Biol. 1991, 220, 435.
116. (c) Moews, P. C.; Knox, J. R.; Dideberg, O.; Charlier, P.; Frere, J. M. Proteins 1990, 7, 156.
117. (d) Herzberg, O.; Moult, J. Science 1987, 236, 694.
118. -1 at room temperature (Wagner, P.; Sedon, J. H.; Lindstrom, M. J. J. Am. Chem. Soc. 1978, 100, 2579). For a β-thiovinyl radical, the expulsion of thiyl radical should occur even more rapidly. See: (a) Benati, L.; Capella, L.; Montevecchi, P. C.; Spagnola, P. J. Org. Chem. 1994, 59, 2818. (b) Griesbaum, K. Angew. Chem., Int. Ed. Engl. 1970, 9, 273.
119. -1 at room temperature (Wagner, P.; Sedon, J. H.; Lindstrom, M. J. J. Am. Chem. Soc. 1978, 100, 2579). For a β-thiovinyl radical, the expulsion of thiyl radical should occur even more rapidly. See: (a) Benati, L.; Capella, L.; Montevecchi, P. C.; Spagnola, P. J. Org. Chem. 1994, 59, 2818. (b) Griesbaum, K. Angew. Chem., Int. Ed. Engl. 1970, 9, 273.
120. -1 at room temperature (Wagner, P.; Sedon, J. H.; Lindstrom, M. J. J. Am. Chem. Soc. 1978, 100, 2579). For a β-thiovinyl radical, the expulsion of thiyl radical should occur even more rapidly. See: (a) Benati, L.; Capella, L.; Montevecchi, P. C.; Spagnola, P. J. Org. Chem. 1994, 59, 2818. (b) Griesbaum, K. Angew. Chem., Int. Ed. Engl. 1970, 9, 273.
121. (a) McKean, D. R.; Parrinello, G.; Renaldo, A. F.; Stille, J. K. J. Org. Chem. 1987, 52, 422.
122. (b) Stille, J. K.; Groh, B. L. J. Am. Chem. Soc. 1987,109, 813.
123. (d) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
124. (e) Scott, W. J.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 3033.
125. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
126. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
127. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
128. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
129. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
130. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
131. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
132. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
133. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
134. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
135. For examples of palladium-catalyzed reactions on β-lactam ring systems, see: (a) Barrett, D.; Terasawa, T.; Okuda, S.; Kawabata, K.; Yasuda, N.; Kamimura, T.; Sakane, K.; Takaya, T. J. Antibiot. 1997, 50, 100. (b) Armitage, M. A.; Lathbury, D. C.; Sweeney, J. B. Tetrahedron Lett. 1995, 36, 775. (c) Burwood, M.; Davies, B.; Diaz, I.; Grigg, R.; Molina, P.; Sridharan, V.; Hughes, M. Tetrahedron Lett. 1995, 36, 9053. (d) Rano, T. A.; Greenlee, M. L.; DiNinno, F. P. Tetrahedron Lett. 1990, 31, 2853. (e) Cook, G. K.; Hornback, W. J.; Jordan, C. L.; McDonald, J. H.; Munroe, J. E. J. Org. Chem. 1989, 54, 5828. (f) Farina, V.; Baker, S. R.; Hauck, S. I. J. Org. Chem. 1989, 54, 4962. (g) Farina, V.; Baker, S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739. (h) Farina, V.; Baker, S. R.; Sapino, C. Tetrahedron Lett. 1988, 29, 6043. (i) Kant, J.; Walker, D. G. In The Organic Chemistry of β-Lactams, Georg, G. I., Ed.; VCH Publishers: New York, 1993; pp 121-196. (j) Researchers at SmithKline Beecham have patented (world patent number WO 9318044-A) interesting chemistry of cephalosporin triflates where, in the presence of Hunig's base, novel [4 + 2]-cycloadducts or substitution products are obtained. For reactions involving pyrrole, only the substitution product is observed. For these reactions, an allenyl intermediate is presumed, and regiochemistry of addition to this species is dependent on the oxidation state of sulfur (n = 0 or 1). Readers may refer to the following articles: (a) Elliott, R. L.; Nicholson, N. H.; Peaker, F. E.; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1994, 59, 1606. (b) Elliott, R. L,; Takle, A. K.; Tyler, J. W.; White, J. J. Org. Chem. 1993, 58, 6954. equation presented
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