Two Practical and Efficient Approaches to Fluorinated and Nonfluorinated Chiral β-Imino Sulfoxides

Journal of Organic Chemistry

Volumn 63, Issue 18, 1998, Pages 6210-6219

  Fustero, Santos ^a   Navarro, Antonio ^a   Pina, Belén ^a   Asensio, Amparo ^a   Bravo, Pierfrancesco ^b   Crucianelli, Marcello ^b   Volonterio, Alessandro ^b   Zanda, Matteo ^b  

^a UNIVERSITY OF VALENCIA   (Spain)

^b POLITECNICO DI MILANO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000740681     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo980336f     Document Type: Article

References (106)

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6. (e) For a review see also: Resnati, G. Tetrahedron 1993, 49, 9385.
7. (f) Resnati, G.; Soloshonok, V. A. Tetrahedron Symposia-in Print-no. 58. Tetrahedron 1996, 52, 1, 319.
8. See for example: (a) Arnone, A.; Bravo, P.; Frigerio, M.; Viani. F.; Cavicchio, G.; Crucianelli, M. J. Org. Chem. 1994, 59, 3459. (b) Arnone, A.; Bravo, P.; Frigerio, M.; Salani, G.; Viani. F.; Zappalà, C.; Cavicchio, G.; Crucianelli, M. Tetrahedron 1995, 57, 8289. (c) Hui-Ping, G.; Chang-Ming, H. Synthesis 1996, 1363.
9. See for example: (a) Arnone, A.; Bravo, P.; Frigerio, M.; Viani. F.; Cavicchio, G.; Crucianelli, M. J. Org. Chem. 1994, 59, 3459. (b) Arnone, A.; Bravo, P.; Frigerio, M.; Salani, G.; Viani. F.; Zappalà, C.; Cavicchio, G.; Crucianelli, M. Tetrahedron 1995, 57, 8289. (c) Hui-Ping, G.; Chang-Ming, H. Synthesis 1996, 1363.
10. See for example: (a) Arnone, A.; Bravo, P.; Frigerio, M.; Viani. F.; Cavicchio, G.; Crucianelli, M. J. Org. Chem. 1994, 59, 3459. (b) Arnone, A.; Bravo, P.; Frigerio, M.; Salani, G.; Viani. F.; Zappalà, C.; Cavicchio, G.; Crucianelli, M. Tetrahedron 1995, 57, 8289. (c) Hui-Ping, G.; Chang-Ming, H. Synthesis 1996, 1363.
11. A number of fluorine-containing amino acids have been synthesized and studied as potential enzyme inhibitors. Amino acids containing the trifluoromethyl group are also potential antimetabolites because of the relatively nontoxic and stable nature of this group. See for example: (a) Fluorine-containig Amino Acids: Synthesis and Properties; Kukhar, V. P., Soloshonok, V. A., Eds.; Wiley: Chichester, 1994. (b) Sakai, T.; Yan, F.; Kashino, S.; Uneyama, K. Tetrahedron 1996, 52, 233. (c) Osipov, S. N.; Golubev, A. S.; Sewald, N.; Michel, T.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. J. Org. Chem. 1996, 61, 7521. (d) Bravo, P.; Capelli, S.; Meille, S. V.; Viani, F.; Zanda, M.; Kukhar, V. P.; Soloshonok, V. A. Tetrahedron: Asymmetry 1994, 5, 2009. (e) Soloshonok, V. A.; Fokina, N. A.; Rybakova, A. V.; Shishkina, I. P.; Galushko, S. V.; Sorochinsky, A. E.; Kukhar, V. P. Tetrahedron: Asymmetry 1995, 7, 1601. (f) Bégué, J.-P.; Bonnet-Delpon, D. Trifluoromethylated Amino Alcohols: New Synthetic Approaches and Medicinal Targets. In Biomedical Frontiers of Fluorine Chemistry; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.; American Chemical Society: Washington, DC, 1996; pp 59-72.
12. A number of fluorine-containing amino acids have been synthesized and studied as potential enzyme inhibitors. Amino acids containing the trifluoromethyl group are also potential antimetabolites because of the relatively nontoxic and stable nature of this group. See for example: (a) Fluorine-containig Amino Acids: Synthesis and Properties; Kukhar, V. P., Soloshonok, V. A., Eds.; Wiley: Chichester, 1994. (b) Sakai, T.; Yan, F.; Kashino, S.; Uneyama, K. Tetrahedron 1996, 52, 233. (c) Osipov, S. N.; Golubev, A. S.; Sewald, N.; Michel, T.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. J. Org. Chem. 1996, 61, 7521. (d) Bravo, P.; Capelli, S.; Meille, S. V.; Viani, F.; Zanda, M.; Kukhar, V. P.; Soloshonok, V. A. Tetrahedron: Asymmetry 1994, 5, 2009. (e) Soloshonok, V. A.; Fokina, N. A.; Rybakova, A. V.; Shishkina, I. P.; Galushko, S. V.; Sorochinsky, A. E.; Kukhar, V. P. Tetrahedron: Asymmetry 1995, 7, 1601. (f) Bégué, J.-P.; Bonnet-Delpon, D. Trifluoromethylated Amino Alcohols: New Synthetic Approaches and Medicinal Targets. In Biomedical Frontiers of Fluorine Chemistry; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.; American Chemical Society: Washington, DC, 1996; pp 59-72.
13. A number of fluorine-containing amino acids have been synthesized and studied as potential enzyme inhibitors. Amino acids containing the trifluoromethyl group are also potential antimetabolites because of the relatively nontoxic and stable nature of this group. See for example: (a) Fluorine-containig Amino Acids: Synthesis and Properties; Kukhar, V. P., Soloshonok, V. A., Eds.; Wiley: Chichester, 1994. (b) Sakai, T.; Yan, F.; Kashino, S.; Uneyama, K. Tetrahedron 1996, 52, 233. (c) Osipov, S. N.; Golubev, A. S.; Sewald, N.; Michel, T.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. J. Org. Chem. 1996, 61, 7521. (d) Bravo, P.; Capelli, S.; Meille, S. V.; Viani, F.; Zanda, M.; Kukhar, V. P.; Soloshonok, V. A. Tetrahedron: Asymmetry 1994, 5, 2009. (e) Soloshonok, V. A.; Fokina, N. A.; Rybakova, A. V.; Shishkina, I. P.; Galushko, S. V.; Sorochinsky, A. E.; Kukhar, V. P. Tetrahedron: Asymmetry 1995, 7, 1601. (f) Bégué, J.-P.; Bonnet-Delpon, D. Trifluoromethylated Amino Alcohols: New Synthetic Approaches and Medicinal Targets. In Biomedical Frontiers of Fluorine Chemistry; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.; American Chemical Society: Washington, DC, 1996; pp 59-72.
14. A number of fluorine-containing amino acids have been synthesized and studied as potential enzyme inhibitors. Amino acids containing the trifluoromethyl group are also potential antimetabolites because of the relatively nontoxic and stable nature of this group. See for example: (a) Fluorine-containig Amino Acids: Synthesis and Properties; Kukhar, V. P., Soloshonok, V. A., Eds.; Wiley: Chichester, 1994. (b) Sakai, T.; Yan, F.; Kashino, S.; Uneyama, K. Tetrahedron 1996, 52, 233. (c) Osipov, S. N.; Golubev, A. S.; Sewald, N.; Michel, T.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. J. Org. Chem. 1996, 61, 7521. (d) Bravo, P.; Capelli, S.; Meille, S. V.; Viani, F.; Zanda, M.; Kukhar, V. P.; Soloshonok, V. A. Tetrahedron: Asymmetry 1994, 5, 2009. (e) Soloshonok, V. A.; Fokina, N. A.; Rybakova, A. V.; Shishkina, I. P.; Galushko, S. V.; Sorochinsky, A. E.; Kukhar, V. P. Tetrahedron: Asymmetry 1995, 7, 1601. (f) Bégué, J.-P.; Bonnet-Delpon, D. Trifluoromethylated Amino Alcohols: New Synthetic Approaches and Medicinal Targets. In Biomedical Frontiers of Fluorine Chemistry; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.; American Chemical Society: Washington, DC, 1996; pp 59-72.
15. A number of fluorine-containing amino acids have been synthesized and studied as potential enzyme inhibitors. Amino acids containing the trifluoromethyl group are also potential antimetabolites because of the relatively nontoxic and stable nature of this group. See for example: (a) Fluorine-containig Amino Acids: Synthesis and Properties; Kukhar, V. P., Soloshonok, V. A., Eds.; Wiley: Chichester, 1994. (b) Sakai, T.; Yan, F.; Kashino, S.; Uneyama, K. Tetrahedron 1996, 52, 233. (c) Osipov, S. N.; Golubev, A. S.; Sewald, N.; Michel, T.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. J. Org. Chem. 1996, 61, 7521. (d) Bravo, P.; Capelli, S.; Meille, S. V.; Viani, F.; Zanda, M.; Kukhar, V. P.; Soloshonok, V. A. Tetrahedron: Asymmetry 1994, 5, 2009. (e) Soloshonok, V. A.; Fokina, N. A.; Rybakova, A. V.; Shishkina, I. P.; Galushko, S. V.; Sorochinsky, A. E.; Kukhar, V. P. Tetrahedron: Asymmetry 1995, 7, 1601. (f) Bégué, J.-P.; Bonnet-Delpon, D. Trifluoromethylated Amino Alcohols: New Synthetic Approaches and Medicinal Targets. In Biomedical Frontiers of Fluorine Chemistry; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.; American Chemical Society: Washington, DC, 1996; pp 59-72.
16. A number of fluorine-containing amino acids have been synthesized and studied as potential enzyme inhibitors. Amino acids containing the trifluoromethyl group are also potential antimetabolites because of the relatively nontoxic and stable nature of this group. See for example: (a) Fluorine-containig Amino Acids: Synthesis and Properties; Kukhar, V. P., Soloshonok, V. A., Eds.; Wiley: Chichester, 1994. (b) Sakai, T.; Yan, F.; Kashino, S.; Uneyama, K. Tetrahedron 1996, 52, 233. (c) Osipov, S. N.; Golubev, A. S.; Sewald, N.; Michel, T.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. J. Org. Chem. 1996, 61, 7521. (d) Bravo, P.; Capelli, S.; Meille, S. V.; Viani, F.; Zanda, M.; Kukhar, V. P.; Soloshonok, V. A. Tetrahedron: Asymmetry 1994, 5, 2009. (e) Soloshonok, V. A.; Fokina, N. A.; Rybakova, A. V.; Shishkina, I. P.; Galushko, S. V.; Sorochinsky, A. E.; Kukhar, V. P. Tetrahedron: Asymmetry 1995, 7, 1601. (f) Bégué, J.-P.; Bonnet-Delpon, D. Trifluoromethylated Amino Alcohols: New Synthetic Approaches and Medicinal Targets. In Biomedical Frontiers of Fluorine Chemistry; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.; American Chemical Society: Washington, DC, 1996; pp 59-72.
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73. For synthesis of chiral alkynyl sulfoxides, see: (a) Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. J. Org. Chem. 1987, 52, 1078. (b)See ref 27b.
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76. (c) Alternatively, fluorinated N-unsubstituted β-enamino sulfoxides have been prepared by using N-trimethylsilyl iminophosphoranes as already indicated (see ref 17b).
77. For preliminary communications, see: (a) Bravo, P.; Cavicchio, G.; Crucianelli, M.; Markovsky, A. L.; Volonterio, A.; Zanda, M. Synlett 1996, 887. (b) Fustero, S.; Navarro, A.; Asensio, A. Tetrahedron Lett. 1997, 38, 4891. Corrigenda: Tetrahedron Lett. 1997, 38, 6477.
78. For preliminary communications, see: (a) Bravo, P.; Cavicchio, G.; Crucianelli, M.; Markovsky, A. L.; Volonterio, A.; Zanda, M. Synlett 1996, 887. (b) Fustero, S.; Navarro, A.; Asensio, A. Tetrahedron Lett. 1997, 38, 4891. Corrigenda: Tetrahedron Lett. 1997, 38, 6477.
79. These compounds can also be synthesized on a large scale by using the DAG methodology. See for example: (a) Guerrero de la Rosa, V.; Ordoñez, M.; Llera, J. M.; Alcudia, F. Synthesis 1995, 761. (b) El Ouazzani, H.; Khiar, N.; Fernández, I.; Alcudia, F. J. Org. Chem. 1997, 62, 287.
80. These compounds can also be synthesized on a large scale by using the DAG methodology. See for example: (a) Guerrero de la Rosa, V.; Ordoñez, M.; Llera, J. M.; Alcudia, F. Synthesis 1995, 761. (b) El Ouazzani, H.; Khiar, N.; Fernández, I.; Alcudia, F. J. Org. Chem. 1997, 62, 287.
81. (a) When method 2 was employed, the excess of sulfoxide (R)-2 could be recovered quantitatively by flash chromatography (FC). (b) The use of only 1 equiv of LDA (or, alternatively, lithiated sulfoxide 2) led, in all cases, to yields lower than 50%. See also ref 11 and literature cited therein.
82. See for example: Cimarelli, C.; Palmieri, G. J. Org. Chem. 1996, 61, 5557. Of particular synthetic interest is the chemoselective cleavage of the N-PMP group of β-aminosulfoxides, obtained by hydride-promoted reduction of β-iminosulfoxides 4 with ceric ammonium nitrate, which does not affect the stereogenic sulfinyl group. See ref 30a.
83. 2 are aliphatic groups. The thermal instability of the N-alkyl imidoyl chlorides 1 derived from aliphatic carboxylic acids (see refs 9 and 10) and their, in general, lower reactivity coupled with the fact that these systems have already been successfully prepared by condensation or Andersen-type reactions, as described by Garcia Ruano et al. (see ref 21d), are some of the reasons for our choice.
84. In one case this reaction was accompanied by an unexpected side reaction. Addition of (2-methoxycarbonylphenyl)imino trifluoroacetimidoyl chloride Is to lithiated (72)-(+)-2a produced the N-(2-hydroxycarbonyl-phenyl )imino derivative 4s, as a nearly unique product. Hydrolysis of the methyl ester functionality may be explained by postulating that the intermediate lithiated β-sulfmyl enamine 3s undergoes an intramolecular Dieckmann-type cyclization, producing the unstable cyclic derivative A. Under aqueous workup conditions, the final product 4s can be produced by retro-condensation. Nevertheless, it cannot be ruled out that the carboxylic acid might also emerge by simple hydrolysis of the ester under alkaline conditions as suggested by one of the referees. chemical equation presented.
85. Very poor yields were always obtained for these derivatives (0-30%)(refs 21a,c and25a).
86. The term "aza-Wittig reaction" is adopted in this paper for reasons of clarity, due to its widespread use in the literature. The name "aza-Wittig" arises from the similarity between this reaction, involving iminophosphoranes, and the true Wittig reaction, which makes use of carbon-phosphorus ylides. However, it must be recognized that the former reaction was discovered by Staudinger: (a) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635. (b) Staudinger, H.; Hauser, E. Helv. Chim. Acta 1921, 4, 861. We thank Dr. Vadim A. Soloshonok, National Industrial Research Institute of Nagoya, Japan, for pointing this out. The fact that "Staudinger reaction", which would be more appropriate, is the well-established name for two other important processes, namely, the reaction between azides and triphenylphosphine, as well as the reaction between ketenes and imines, leading to β-lactams, led us to use the term "aza-Wittig reaction" to avoid confusion. For recent reviews see: (c) Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197. (d) Johnson, A. W.; Kasha, W. C.; Starzewsky, K. A. O.; Dixon, D. A. Ylides and Imines of Phosphorus; John Wiley: New York, 1993; Chapter 13.
87. The term "aza-Wittig reaction" is adopted in this paper for reasons of clarity, due to its widespread use in the literature. The name "aza-Wittig" arises from the similarity between this reaction, involving iminophosphoranes, and the true Wittig reaction, which makes use of carbon-phosphorus ylides. However, it must be recognized that the former reaction was discovered by Staudinger: (a) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635. (b) Staudinger, H.; Hauser, E. Helv. Chim. Acta 1921, 4, 861. We thank Dr. Vadim A. Soloshonok, National Industrial Research Institute of Nagoya, Japan, for pointing this out. The fact that "Staudinger reaction", which would be more appropriate, is the well-established name for two other important processes, namely, the reaction between azides and triphenylphosphine, as well as the reaction between ketenes and imines, leading to β-lactams, led us to use the term "aza-Wittig reaction" to avoid confusion. For recent reviews see: (c) Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197. (d) Johnson, A. W.; Kasha, W. C.; Starzewsky, K. A. O.; Dixon, D. A. Ylides and Imines of Phosphorus; John Wiley: New York, 1993; Chapter 13.
88. The term "aza-Wittig reaction" is adopted in this paper for reasons of clarity, due to its widespread use in the literature. The name "aza-Wittig" arises from the similarity between this reaction, involving iminophosphoranes, and the true Wittig reaction, which makes use of carbon-phosphorus ylides. However, it must be recognized that the former reaction was discovered by Staudinger: (a) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635. (b) Staudinger, H.; Hauser, E. Helv. Chim. Acta 1921, 4, 861. We thank Dr. Vadim A. Soloshonok, National Industrial Research Institute of Nagoya, Japan, for pointing this out. The fact that "Staudinger reaction", which would be more appropriate, is the well-established name for two other important processes, namely, the reaction between azides and triphenylphosphine, as well as the reaction between ketenes and imines, leading to β-lactams, led us to use the term "aza-Wittig reaction" to avoid confusion. For recent reviews see: (c) Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197. (d) Johnson, A. W.; Kasha, W. C.; Starzewsky, K. A. O.; Dixon, D. A. Ylides and Imines of Phosphorus; John Wiley: New York, 1993; Chapter 13.
89. The term "aza-Wittig reaction" is adopted in this paper for reasons of clarity, due to its widespread use in the literature. The name "aza-Wittig" arises from the similarity between this reaction, involving iminophosphoranes, and the true Wittig reaction, which makes use of carbon-phosphorus ylides. However, it must be recognized that the former reaction was discovered by Staudinger: (a) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635. (b) Staudinger, H.; Hauser, E. Helv. Chim. Acta 1921, 4, 861. We thank Dr. Vadim A. Soloshonok, National Industrial Research Institute of Nagoya, Japan, for pointing this out. The fact that "Staudinger reaction", which would be more appropriate, is the well-established name for two other important processes, namely, the reaction between azides and triphenylphosphine, as well as the reaction between ketenes and imines, leading to β-lactams, led us to use the term "aza-Wittig reaction" to avoid confusion. For recent reviews see: (c) Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197. (d) Johnson, A. W.; Kasha, W. C.; Starzewsky, K. A. O.; Dixon, D. A. Ylides and Imines of Phosphorus; John Wiley: New York, 1993; Chapter 13.
90. (a) Kirsanov, A. V. Izv. Akad. Nauk SSSR 1950, 426; Chem. Abstr. 1951, 45, 1503.
91. (a) Kirsanov, A. V. Izv. Akad. Nauk SSSR 1950, 426; Chem. Abstr. 1951, 45, 1503.
92. (b) Horner, L.; Oediger, H. Liebigs Ann. Chem. 1959, 627, 142.
93. (c) Leffler, J. E.; Temple, R. D. J. Am. Chem. Soc. 1967, 89, 5235.
94. To date we have not been able to obtain the pure single diastereoisomers by chromatography (FC or MPLC).
95. Meyers, A. I.; Novachek, K. A. Tetrahedron Lett. 1996, 37, 1747.
96. 4α: Z imino configuration. 4β: E imino configuration, 4γ: Z enamino configuration. 4δ: E enamino configuration.
97. 19F NMR spectroscopy.
98. 3 solution at 50 °C for 3 weeks. The peculiar behavior of 4p may be explained by assuming the presence of a charge-transfer interaction between the π-electron-deficient pyridine and the π-electron-rich p-anisidine aromatic rings, which should stabilize the E iminic isomer.
99. In contrast with this result, it has been reported in the literature (see ref 25a) that compound 4c, initially obtained only as an Z imino tautomer, undergoes a complete Z → E imine isomerization by standing at room temperature for several days. For comparison, we have also used the methodology described in ref 25a for preparing 4c (29%). We found that both methods afforded the same 9:1 mixture of Z/E imino tautomers. In any case we could not observe Z→ E imine isomerization.
100. F -72.1 to -62.1 ppm. Similar isomerizations have also been observed for related compounds (see ref 17b).
101. It must be emphasized that certain ambiguities exist in the literature regarding the stereochemistry of the double bond of the iminic and enaminic tautomers of derivatives 4 (see ref 21). Thus, for example, Ogura assigned an E enamino configuration to N-alkyl β-enamino sulfoxides resulting from condensations of β-ketosulfoxides with aliphatic amines (see ref 21e), while the same author proposed the opposite Z enamino configuration for related compounds obtained in a similar manner (see ref 21b). This, and other contradictory results (see refs 21a,c), can be explained by assuming that the reaction conditions, as well as the methodology used to prepare the target βimino sulfoxides, are critical in obtaining one or the other tautomer.
102. Gaussian 94, Revision C.3; Frisch, M. J.; Schlegel, Trucks, G. W.; H. B.; Gill, P. M. W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G. A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.; Nanayakkara, A.; Challacombe, N.; Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andrés, J. L.; Replogle, E. S.; Gomperts, R.; Martín, R. L.; Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. J. P.; Head-Gordon, M.; González, C.; Pople, J. A.; Gaussian Inc., Pittsburgh, PA, 1995.
103. Lorente, A., Ph.D. Thesis, Universidad Autónoma de Madrid, 1997. See also ref 21d.
104. It must be pointed out that good agreement between theory and experimental exists only for the highest level of theory (HF/6-31G*//HF/6-31G*).
105. A different result was found in the case of the N-aryl fluorine-free derivative 4B (Chart 2 and Table 3). HF/6-31G* calculations for 4B predict the E imino (4β) configuration as the most stable tautomer. Accordingly, this compound has been obtained by Garcia Ruano et al. (see ref 48) as an E imino/Z imino/Z enamino (50/10/40) mixture from the N-PMP imine of acetone, following an Andersen-like method.
106. Kozerski, L.; Kawecki, R.; Bednarek, E. Magn. Reson. Chem. 1987, 25, 712.