An efficient asymmetric synthesis of anti-1,2-disubstituted taurine derivatives through nucleophilic addition of phenylmethanesulfonate to various N-acylimines in the presence of 1,2:5,6-di-O-isopropylidene-a-D-allofuranose as a chiral auxiliary is described. The taurine derivatives were obtained in three steps with good overall yields (36-61%) and excellent enantiomeric excesses (83-98%). The diastereomeric excesses of 15-91% could be improved to 90-98% by column chromatography or recrystallization. The relative and absolute configurations of the products were determined by means of an X-ray crystal structure analysis.Sulfonic acids and their derivatives are important biologically active constituents of mammals, marine algae, fish, and shellfish. 1 The best known are 2-aminoethanesulfonic acid (taurine) and related compounds such as 3-aminopropanesulfonic acid (homotaurine), 2-carbamimidamidoethanesulfonic acid (N-guanidinotaurine), cysteic acid, and 2-hydroxyethanesulfonic acid (isethionic acid) ( Figure 1). Taurine is found in relatively high concentrations in the central nervous system, brain, heart, retina, and muscles, and is involved in various physiological processes such as brain development, neurotransmission, and immunomodulation. 2In view of the important physiological effects of these naturally occurring aminosulfonic acids, which can be regarded as sulfur analogues of amino acids, the development of new diastereo-and enantioselective methods for their synthesis is highly desirable.Several reports have already been devoted to the synthesis of taurine derivatives. 1-Substituted taurines have been synthesized from olefins, 3 from b-amino secondary alcohols, 4 and from epoxides. 5 2-Substituted taurines have been prepared from b-amino primary alcohols, 6 from aziridines, 7 and from 2-nitroalkanesulfonic acids. 8 1,1-Disubstituted taurines are available from ketones through Corey-Chaykovsky epoxidation, episulfidation, and ammonia-induced ring cleavage, followed by oxidation with performic acid. 9 1,2-Disubstituted taurines have been prepared from olefins 9,10 and from epoxides. 5 2,2-Disubstituted taurines have been synthesized from aziridines, 11 from amino alcohols, 6f and from ketones through the Strecker amino acid synthesis. 12Our group has described an efficient asymmetric synthesis of 2-substituted and 1,2-disubstituted taurine derivatives through aza-Michael addition of the enantiopure hydrazines (2S)-2-(methoxymethyl)pyrrolidin-1-amine (SAMP) or (2R,3aR,6aR)-2-(methoxymethyl)hexahydrocyclopenta[b]pyrrol-1(2H)-amine (RAMBO) to a,b-unsaturated sulfonates in the presence of a Lewis acid catalyst. 13In our ongoing research on the asymmetric synthesis of sulfonic acid derivatives, we planned to gain access to 1,2-disubstituted taurine derivatives through nucleophilic addition to an N-acylimine of a chiral phenylmethanesulfonate bearing an enantiopure sugar auxiliary.In previous communications and a full paper, 14 we reported on efficient asymmetric electrophilic a-substitution reactions of various a...

The asymmetric synthesis of a,b-disubstituted g-bisalkoxycarbonyl sulfonates is reported. The synthesis is based on the Michael addition of a lithiated enantiopure sulfonate bearing a cheap chiral sugar auxiliary to Knoevenagel acceptors. The reaction proceeds with high asymmetric inductions (ds = 69-96%) and good yields (62-79%). The absolute configuration was determined by Xray crystal-structure analysis.Sulfonic acid derivatives constitute an important class of organic compounds, which exist in a large number of natural products. They are also present in synthetic compounds with important biological or pharmacological activities, such as antiulcer, antibacterial, antipseudomonal, and squalene synthase inhibition activities. 1 On the other hand, sulfonates are of interest as bioactive isosteres of carboxylates, phosphates, and sulfates such as phospholipids, sulfated steroid conjugates, and oligonucleotides. 2 However, only a few asymmetric syntheses of this important class of compounds are described in the literature. 3 In continuation of our research on the asymmetric synthesis of sulfonic acid derivatives, 4 we now wish to report a convenient diastereo-and enantioselective approach for the synthesis of a,b-disubstituted g-bisalkoxycarbonyl sulfonates.The asymmetric synthesis of the title compounds is based on a stoichiometric approach employing 1,2:5,6-di-O-isopropylidene-a-D-allofuranose as a cheap chiral sugar auxiliary. As shown in Scheme 1, the enantiopure sulfonate 1 was deprotonated with n-butyllithium in THF and allowed to react with the Knoevenagel acceptor 2a to give the Michael adduct 3a in good yield (79%) and high diastereoselectivity (77%).We explored the generality of this reaction with a wide range of Michael acceptors bearing different substituents. The desired products 3a-j were obtained with one exception in good yields (10, 62-79%) and high diastereoselectivities (ds = 69-96%). The results are summarized in Table 1.The variation of the substituents of the Michael acceptors indicated a strong influence on the diastereoselectivity of the reaction. Michael acceptors containing heterocycles (2e,f) afforded the Michael products in good yields (62% and 69%, respectively) and excellent diastereoselectivities (82% and 96%, respectively). The more sterically hindered alkene 2g reacted with sulfonate 1 in high diastereoselectivity (87%), whereas the aliphatic Michael acceptor 2h gave only a moderate diastereoselectivity (69%). The effect of the electron-withdrawing groups of the Michael acceptor was also investigated. The replacement of an ester group with a cyanide function did not lead to any significant changes in yield and diastereoselectivity (entry 9). A significant difference was observed, however, when two tert-butyl ester groups instead of the two methyl ester were used (entry 10). This result may be explained by the steric hindrance caused by the two tert-butyl groups.In all of these cases, only three out of four possible diastereomers could be detected. The major diastereomers could be i...

A s y m m e t r i c S y n t h e s i s o f a -P h eAbstract: An efficient route to a-phenyl-g-hetero (O, S, Se, Cl)-substituted isopropyl sulfonates via S N 2-ring opening of g-sultones, easily available by asymmetric synthesis from chiral lithiated sulfonates, is described. The title compounds are obtained in very good overall yields of 65-86% over three steps and excellent diastereoand enantiomeric excesses (de = 94-96%, ee ≥ 98%).Derivatives of sulfonic acids are important constituents of living organisms. 1 Probably, the best known are 2-aminoethanesulfonic acid (taurine) and related compounds. In our ongoing research concerning the chemistry of sultones we have now developed an efficient diastereo-and enantioselective approach to several classes of these derivatives.Sultones are important heterocyclic intermediates which can react with a variety of nucleophiles cleaving the carbon-oxygen bond to introduce an alkylsulfonic acid functionality. 2 Several reports have been devoted to the synthesis and ring-opening reactions of sultones. 2-6 Before our studies, neither an asymmetric strategy nor the diastereoselectivity of these ring-opening reactions have been investigated. In previous communications and a full paper, we have described efficient asymmetric electrophilic a-substitutions of benzyl sulfonates bearing 1,2:5,6-di-O-isopropylidene-a-D-allofuranose as a chiral auxiliary with various alkyl halides and nitroalkenes. 7,8 In subsequent investigations we extended this methodology using allylic halides as electrophiles in the diastereo-and enantioselective synthesis of various a,g-substituted gsultones. 9Moreover, we recently reported a highly efficient asymmetric synthesis of enantiopure g-azido, g-alkoxy and ghydroxy sulfonates B via diastereoselective ring-opening of various enantiopure g-sultones A (Scheme 1). 10-12 The products could be obtained in good yields and excellent diastereo-and enantiomeric excesses (de, ee ≥ 98%).We now wish to describe the successful application of these enantiopure g-sultones in the asymmetric synthesis of g-thiocyanato sulfonate 4a, g-selenocyanato sulfonate 4b, g-chloro sulfonate 4c, g-acetoxy sulfonate 4d, and gpropionyloxy sulfonate 4e.As shown in Scheme 2, the ring opening of sultone 1 with various hetero nucleophiles could be performed smoothly in DMF or DMSO as solvent under anhydrous conditions. The resulting sodium and potassium sulfonates 2 could be directly converted into their corresponding isopropyl esters in a two-step sequence. Protonation with methanolic HCl gave the sulfonic acids 3 and subsequent treatment with triisopropyl orthoformate in dichloromethane provided the desired isopropyl sulfonates 4 in good overall yields (65-86%) and excellent diastereo-and enantiomeric excesses (de = 94-96%, ee ≥ 98%, Table 1). The ee values of the products were determined by GC and HPLC analysis using chiral stationary phases by comparison with the racemate, showing that the ring opening of sultone 1 proceeded without epimerization at the a-position of the sulfonyl group....

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Ring opening reactions O 0132Asymmetric Synthesis of α-Phenyl-γ-hetero-substituted Isopropyl Sulfonates via Diastereoselective Ring-Opening of γ-Sultones. -The ring opening of sultone (I) with various heteronucleophiles is performed smoothly in DMF or DMSO as solvent under anhydrous conditions, without epimerization at the α-position of the sulfonyl group. The asymmetric access to sulfonates (IV), (VI), (VIII), (X), and (XI) is achieved via a simple three-step reaction sequence in very good overall yields (65-86%) and excellent diastereo-and enantiomeric selectivities. -(ENDERS*, D.; IFFLAND, D.; Synthesis 2007Synthesis , 12, 1837Synthesis -1840 Inst. Org. Chem.,