Asymmetric Synthesis of 1,2-anti-Disubstituted Taurine Derivatives

Abstract

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...

A Versatile Synthesis of Various Substituted Taurines from Vicinal Amino Alcohols and Aziridines

“…[19] It has been reported that taurine can be synthesized from heterocyclic thiazoline by bromine oxidation. [20] However, the thiazolines need to be prepared from vicinal amino mercaptans, most of which are commercially unavailable and are uncomfortably odorous.…”

Recent Developments in Asymmetric Organocatalytic Domino Reactions

“…[60] These novel processes opened an efficient and enantioselective entry to the tricyclic pyrroloindole core, which is a characteristic structural unit of many bioactive natural products. As shown in Scheme 25, a series…”

Organocatalytic strategies for the asymmetric functionalization of indoles

“…The synthesis has been carried out under two different reaction conditions (MTBE, 123 or in toluene and 4 Å MS) 124 and provided an efficient and asymmetric entry to synthetically useful and potentially bioactive (R)-3-substituted 3H-pyrrolo[1,2-a]indoles (83) in 40-71% yields and 85 to >99% ee or 57-81% yields and 71-96% ee, respectively. Both reactions worked at room temperature, with 20 mol% of 17, in comparable reaction times (24-96 h or 72 h respectively) and aliphatic enals afforded only traces of 83.…”

“…For example, the introduction of a formyl group on the C-2 position of the indole nucleus allowed a domino reaction between indole-2-carbaldehyde (82) and a,b-unsaturated aldehydes (26) with 17 as the catalyst following an iminium/ enamine activation mode (Scheme 27). The synthesis has been carried out under two different reaction conditions (MTBE, 123 or in toluene and 4 A ˚MS) 124 and provided an efficient and asymmetric entry to synthetically useful and potentially bioactive (R)-3-substituted 3H-pyrrolo[1,2-a]indoles (83) in 40-71% yields and 85 to >99% ee or 57-81% yields and 71-96% ee, respectively. Both reactions worked at room temperature, with 20 mol% of 17, in comparable reaction times (24-96 h or 72 h respectively) and aliphatic enals afforded only traces of 83.…”