(+)-(S)-N-Methylsulfonylphenylalanyl Chloride

[63640-54-0]  · C10H12ClNO3S  · (+)-(S)-N-Methylsulfonylphenylalanyl Chloride  · (MW 261.75)

(chiral reagent for the resolution of racemic alcohols via separation of the corresponding diastereomeric esters1)

Physical Data: mp 84-85 °C; [a]20D +4.3° (c 1.6, THF).

Solubility: readily sol THF, benzene, ether.

Form Supplied in: pale yellow needles; not available commercially.

Preparative Method: prepared from (S)-phenylalanine by reaction with Methanesulfonyl Chloride, followed by Phosphorus(V) Chloride.1b

Purification: the crude compound can be recrystallized from hexane/ether.

Handling, Storage, and Precautions: best if prepared immediately prior to use. Can be stored at 0 °C under nitrogen for several days without appreciable decomposition.

Introduction.

Enantiomerically pure alcohols can frequently be obtained by physical separation of the diastereomeric esters prepared from the racemic alcohols and chiral acids.2 Chiral acids that have been successfully employed for this purpose and are available in either enantiomeric form include o-camphanic acid3 and the monomethyl ester of diacetyltartaric acid.4 No reagent can be considered generally applicable to all alcohols, since the ease of separation of the diastereomeric esters frequently depends on their crystallinity and/or chromatographic properties. A successful resolution is frequently the result of multiple trials and errors with a variety of acids.

N-Sulfonylated a-Amino Acids.

N-Protected derivatives of the natural a-amino acids offer a wide range of potential derivatizing agents.5 Particularly useful are N-arylsulfonyl-a-amino acids,6 many of which are commercially available and produce crystalline ester mixtures from which pure diastereomers can often be isolated by recrystallization. N-Methylsulfonyl-a-amino acids or the corresponding acid chlorides are generally not commercially available, but in some cases have been shown to be superior to the corresponding N-tosyl derivatives (eq 1).1b,7

N-Methylsulfonylphenylalanyl chloride (1) is particularly useful in the derivatization of meso-diols. Mixtures of diastereomeric monoesters can be obtained, from which pure diastereomers are usually isolated by fractional recrystallization and/or chromatography. Chemical transformation of the free hydroxy group, followed by removal of the chiral auxiliary, allows the selective transformation of each prochiral hydroxy group. Isolation of the other diastereomeric ester from the mother liquors, followed by a series of protection-deprotection steps, provides the flexibility of converting 100% of the meso-material into one single enantiomer of the product. Alternatively, by rearranging the order of the chemical transformations, both enantiomers of the product can be obtained (eqs 2 and 3).1,8


1. (a) Terashima, S.; Yamada, S. TL 1977, 1001. (b) Nara, M.; Terashima, S.; Yamada, S. T 1980, 36, 3161.
2. Enantiomers, Racemates and Resolutions; Jacques, J.; Collet, A.; Wilen, S. H., Eds.; Wiley: New York, 1981; pp 332-335.
3. Wilen, S. H.; Collet, A.; Jacques, J. T 1977, 33, 2725.
4. Hübner, M.; Ponsold, K.; Siemann, H. J.; Schwartz, S. ZC 1968, 8, 380.
5. Hashimoto, S.; Kase, S.; Shinoda, T.; Ikegami, S. CL 1989, 1063.
6. (a) Jermyn, M. A. AJC 1967, 20, 2283. (b) Halpern, B.; Westley, J. W. AJC 1966, 19, 1533.
7. Kawamura, K.; Ohta, T.; Otani, G. CPB 1990, 38, 2088.
8. Nara, M.; Terashima, S.; Yamada, S. T 1980, 36, 3171.

Juan C. Jaen

Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA



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