Highly practical methodology for the synthesis of D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids

Journal of the American Chemical Society

Volumn 119, Issue 4, 1997, Pages 656-673

  Myers, Andrew G ^a   Gleason, James L ^a   Yoon, Taeyoung ^a   Kung, Daniel W ^a  

^a CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID SYNTHESIS; ARTICLE; IN VITRO STUDY; METHODOLOGY; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0031047509     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9624073     Document Type: Article

References (108)

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50. (9) See for example: Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1993, 115, 10125. For comprehensive reviews see ref 4 and (a) Koening, K. E. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, 1985; Vol. 5. (b) Bosnich, B. Asymmetric Catalysis; Martinus Nijhoff: Dordrecht, The Netherlands, 1986.
51. See for example: Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1993, 115, 10125. For comprehensive reviews see ref 4 and (a) Koening, K. E. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, 1985; Vol. 5. (b) Bosnich, B. Asymmetric Catalysis; Martinus Nijhoff: Dordrecht, The Netherlands, 1986.
52. See for example: Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1993, 115, 10125. For comprehensive reviews see ref 4 and (a) Koening, K. E. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, 1985; Vol. 5. (b) Bosnich, B. Asymmetric Catalysis; Martinus Nijhoff: Dordrecht, The Netherlands, 1986.
53. For reviews see: (a) Schmidt, U.; Lieberknecht, A.; Wild, J. Synthesis 1988, 159. (b) Schmidt, U.; Hausler, J.; Ohler, E.; Poisel, H. Progress in the Chemistry of Organic Natural Products; Springer-Verlag: Wein, 1979; Vol. 37, p 251.
54. For reviews see: (a) Schmidt, U.; Lieberknecht, A.; Wild, J. Synthesis 1988, 159. (b) Schmidt, U.; Hausler, J.; Ohler, E.; Poisel, H. Progress in the Chemistry of Organic Natural Products; Springer-Verlag: Wein, 1979; Vol. 37, p 251.
55. Myers, A. G.; Yang, B. H.; Chen, H.; Gleason, J. L. J. Am. Chem. Soc. 1994, 116, 9361.
56. Myers, A. G.; Yoon, T.; Gleason, J. L. Tetrahedron Lett. 1995, 36, 4555.
57. It was shown more than 80 years ago that pseudoephedrine undergoes selective N-acylation with both carboxylic acid chlorides and anhydrides. See: (a) Schmidt, E.; Calliesz, F. W. Arch. Pharm. 1912, 250, 154. (b) Mitchell, W. J. Chem. Soc. 1940, 1153. (c) Welsh, L. H. J. Am. Chem. Soc. 1947, 69, 128.
58. It was shown more than 80 years ago that pseudoephedrine undergoes selective N-acylation with both carboxylic acid chlorides and anhydrides. See: (a) Schmidt, E.; Calliesz, F. W. Arch. Pharm. 1912, 250, 154. (b) Mitchell, W. J. Chem. Soc. 1940, 1153. (c) Welsh, L. H. J. Am. Chem. Soc. 1947, 69, 128.
59. It was shown more than 80 years ago that pseudoephedrine undergoes selective N-acylation with both carboxylic acid chlorides and anhydrides. See: (a) Schmidt, E.; Calliesz, F. W. Arch. Pharm. 1912, 250, 154. (b) Mitchell, W. J. Chem. Soc. 1940, 1153. (c) Welsh, L. H. J. Am. Chem. Soc. 1947, 69, 128.
60. Minimizing the volume of hexanes was found to be beneficial for the reaction.
61. For a discussion of the role of lithium chloride in this reaction, see ref 12.
62. Brenner, M.; Huber, W. Helv. Chim. Acta 1953, 36, 1109.
63. Myers, A. G.; Gleason, J. L. Org. Synth., submitted for publication.
64. Tsunoda et al. have also described the enolization (and subsequent Claisen rearrangement) of a glycinamide bearing a free amino group. See: Tsunoda, T.; Tatsuki, S.; Shiraishi, Y.; Akasaka, M.; Ito, S. Tetrahedron Lett. 1993, 34, 3297.
65. The N,N-diallylated product 6 is accompanied by some C-allylated product 7c (13%) and recovered 1 (32%). (20) Care must be exercised when reactions employing an excess of alkylating agent are worked up, for both 1 and its C-alkylation products will undergo N-alkylation when concentrated at ambient temperature in the presence of an alkyl halide. The desired C-alkylation product can be separated from excess alkylating agent by acid/base extraction (see the Experimental Section), thereby avoiding N-alkylation entirely.
66. The distinct orange color dissipates immediately upon addition of alkylating agents, producing a bright yellow suspension.
67. (a) Watson, S. C.; Eastham, J. F. J. Organomet. Chem. 1967, 9, 165.
68. (b) Gall, M.; House, H. O. Organic Syntheses; Wiley: New York, 1988; Collect. Vol. VI, p 121. We have also successfully employed diphenylacetic acid as an indicator for the titration of n-butyllithium (Kofron, W. G.; Baclawski, L. M. J. Org. Chem. 1976, 41, 1879). However, we are aware of two instances where titration with diphenylacetic acid failed to give an accurate titer of n-butyllithium in other laboratories, whereas the titration method of Watson and Eastham was successful. The reasons for the erroneous titrations with diphenylacetic acid were not identified.
69. (b) Gall, M.; House, H. O. Organic Syntheses; Wiley: New York, 1988; Collect. Vol. VI, p 121. We have also successfully employed diphenylacetic acid as an indicator for the titration of n-butyllithium (Kofron, W. G.; Baclawski, L. M. J. Org. Chem. 1976, 41, 1879). However, we are aware of two instances where titration with diphenylacetic acid failed to give an accurate titer of n-butyllithium in other laboratories, whereas the titration method of Watson and Eastham was successful. The reasons for the erroneous titrations with diphenylacetic acid were not identified.
70. 18 column; 220 nm detection). Response factors were determined by the injection of standard solutions of authentic 1, 8, and pseudoephedrine.
71. The mechanism is complicated by the presence of two amide rotamers of 1, essentially nonequilibrating at -78°C.
72. In support of a nucleophilic cleavage mechanism, we find that when a crossover experiment is conducted with a mixture of 1 (0.5 equiv) and 2 (0.5 equiv) using excess LDA (2.5 equiv), products of both sarcosine and glycine transfer to the glycinamide 1, but not the sarcosinamide 2, are observed. This result suggests that the transfer reaction is sensitive to the steric bulk of the amino group, consistent with a nucleophilic addition mechanism.
73. In large-scale alkylation reactions, the rate of addition of lithium diisopropylamide should be modulated to maintain an internal reaction temperature of ≤5°C to avoid decomposition.
74. When solutions of n-butyllithium are added to solutions containing 1, the alkyllithium solution should be added to the inside edge of the flask, such that it runs down the side of the flask before mixing with the bulk solution (or slurry), allowing the reagent to cool to -78°C before mixing. Adding warm (23°C) solutions of n-butyllithium directly into the middle of a solution containing 1 at -78°C will result in significant decomposition.
75. (Trimethylsilyl)methyl chloride was found to be unreactive toward enolate 4. Alkylation of 1 with (trimethylsilyl)methyl iodide resulted in decomposition.
76. Myers, A. G.; Gleason, J. L. J. Org. Chem. 1996, 61, 813.
77. SinhaRoy, R.; Imperiali, B. Tetrahedron Lett. 1996, 37, 2129.
78. Kearney, P. C.; Nowak, M. W.; Zhong, W.; Silverman, S. K.; Lester, H. A.; Dougherty, D. A. Mol. Pharm., submitted for publication.
79. It is generally assumed that the enolization of tertiary amides produces the (Z)-isomer. See: (a) Heathcock, C. H.; Buse, C. T.; Kleschick, W. A.; Pirrung, M. C.; Sohn, J. E.; Lampe, J. J. Org. Chem. 1980, 45, 1066. (b) Evans, D. A.; McGee, L. R. Tetrahedron Lett. 1980, 21, 3975. (c) Evans, D. A.; Tacaks, J. M. Tetrahedron Lett. 1980, 21, 4233.
80. It is generally assumed that the enolization of tertiary amides produces the (Z)-isomer. See: (a) Heathcock, C. H.; Buse, C. T.; Kleschick, W. A.; Pirrung, M. C.; Sohn, J. E.; Lampe, J. J. Org. Chem. 1980, 45, 1066. (b) Evans, D. A.; McGee, L. R. Tetrahedron Lett. 1980, 21, 3975. (c) Evans, D. A.; Tacaks, J. M. Tetrahedron Lett. 1980, 21, 4233.
81. It is generally assumed that the enolization of tertiary amides produces the (Z)-isomer. See: (a) Heathcock, C. H.; Buse, C. T.; Kleschick, W. A.; Pirrung, M. C.; Sohn, J. E.; Lampe, J. J. Org. Chem. 1980, 45, 1066. (b) Evans, D. A.; McGee, L. R. Tetrahedron Lett. 1980, 21, 3975. (c) Evans, D. A.; Tacaks, J. M. Tetrahedron Lett. 1980, 21, 4233.
82. The more rapid elution of D-α-amino acids, relative to their L-antipodes, with Crownpak CR(+) chiral HPLC columns is documented (Instruction Manual, Crownpak CR(+) column, Daicel Chemical Industries).
83. 1H NMR determination of diastereomeric ratios is complicated by the presence of amide rotamers in solution. Diastereomeric pairs of alkylation products exist with different ratios of rotamers, thus requiring the correct identification and integration of all four possible reasonances for a given proton within a pair of diastereomers.
84. See ref 5j and (a) Seebach, D. Angew. Chem., Int. Ed. Engl. 1988, 27, 1624. (b) Seebach, D.; Bossler, H.; Grundler, H.; Shoda, S.-I. Helv. Chim. Acta 1991, 74, 197.
85. See ref 5j and (a) Seebach, D. Angew. Chem., Int. Ed. Engl. 1988, 27, 1624. (b) Seebach, D.; Bossler, H.; Grundler, H.; Shoda, S.-I. Helv. Chim. Acta 1991, 74, 197.
86. (a) Knapp, S.; Hale, J. J.; Bastos, B.; Gibson, F. S. Tetrahedron Lett. 1990, 31, 2109.
87. (b) Knapp, S.; Hale, J. J.; Bastos, B.; Molina, A.; Chen, K. Y. J. Org. Chem. 1992, 57, 6239.
88. N-Boc-pseudoephedrine amides have been used in the preparation of N-Boc-α-amino ketone derivatives. Myers, A. G.; Yoon, T. Tetrahedron Lett. 1995, 36, 9429.
89. For the first practical demonstration of an asymmetric alkylation reaction of a carboxylate derivative (employing a chiral amino alcohol as an auxiliary) see: (a) Meyers, A. I.; Knaus, G.; Kamata, K. J. Am. Chem. Soc. 1974, 96, 268. (b) Meyers, A. I.; Knaus, G.; Kamata, K.; Ford, M. E. J. Am. Chem. Soc. 1974, 98, 567.
90. For the first practical demonstration of an asymmetric alkylation reaction of a carboxylate derivative (employing a chiral amino alcohol as an auxiliary) see: (a) Meyers, A. I.; Knaus, G.; Kamata, K. J. Am. Chem. Soc. 1974, 96, 268. (b) Meyers, A. I.; Knaus, G.; Kamata, K.; Ford, M. E. J. Am. Chem. Soc. 1974, 98, 567.
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92. A related observation was made earlier by Meyers and Temple concerning the hydrolysis of 2-oxazolines, wherein the hydrolysis of β-amino alcohol ester hydrochlorides (resulting from the acid-catalyzed ring opening of 2-oxazolines) occurred under both acidic and basic reaction conditions. See: Meyers, A. I.; Temple, D. L. J. Am. Chem. Soc. 1970, 92, 6646.
93. If required for solubility, methanol or dioxane may be added as a cosolvent.
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97. For substrates with extremely low water solubility, dioxane-water mixtures may be used in the hydrolysis reaction.
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99. For evidence of the blocking of an enolate π-face by a metal alkoxide (and the influence of different metal ions on that blocking) see: Meyers, A. I.; Wunsch, T. J. Org. Chem. 1990, 55, 4233.
100. 1,3 strain as a controlling factor in stereoselective transformations, see: Hoffmann, R. W. Chem. Rev. 1989, 89, 1841.
101. Quirion et al. have investigated the diastereoselective alkylation of amide enolates derived from N-methylphenylglycinol. The sense of diastereoselectivity they observe corresponds with that of pseudoephedrine amide enolate alkylations, but their proposed transition structure is different: Micouin, L.; Schanen, V.; Riche, C.; Chiaroni, A.; Quirion, J.-C.; Husson, H.-P. Tetrahedron Lett. 1994, 35, 7223. See also: Micouin, L.; Varea, T.; Riche. C.; Chiaroni, A.; Quirion, J.-C.; Husson, H.-P. Tetrahedron Lett. 1994, 35, 2529.
102. Quirion et al. have investigated the diastereoselective alkylation of amide enolates derived from N-methylphenylglycinol. The sense of diastereoselectivity they observe corresponds with that of pseudoephedrine amide enolate alkylations, but their proposed transition structure is different: Micouin, L.; Schanen, V.; Riche, C.; Chiaroni, A.; Quirion, J.-C.; Husson, H.-P. Tetrahedron Lett. 1994, 35, 7223. See also: Micouin, L.; Varea, T.; Riche. C.; Chiaroni, A.; Quirion, J.-C.; Husson, H.-P. Tetrahedron Lett. 1994, 35, 2529.
103. (a) Frankel, M.; Katchalski, E. J. Am. Chem. Soc. 1942, 64, 2264.
104. (b) Almeida, J. G.; Anaya, J.; Martin, N.; Grande, M.; Caballero, M. C. Tetrahedron: Asymmetry 1992, 3, 1431.
105. 1H NMR analysis. If desired, the recovered solid can be recrystallized from water and dried in vacuo to afford analytically pure material (typical recovery 83-85%). See: Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals; Pergammon Press: Oxford, 1988; p 266.
106. Dictionary of Organic Compounds. 6th ed.; Chapman and Hall: London, 1996.
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