Novel chiral thiazoline‐containing N―O ligands in the asymmetric addition of diethylzinc to aldehydes: substituent effect on the enantioselectivity

Abstract

Several novel chiral thiazoline primary and tertiary alcohols were easily synthesized from commercially available l‐cysteine in three steps and with high yield. These ligands were subsequently applied to the asymmetric addition of diethylzinc (Et2Zn) to various aldehydes. Products with S configuration were obtained when thiazoline‐containing tertiary alcohol ligands were used as catalysts. The primary alcohol induced corresponding products with R configuration in 68% enantiomeric excess, which was a higher value relative to other N―O ligands possessing a primary alcohol unit in the literature. Furthermore, a plausible transition state model was proposed to explain the observed enantioselectivities. Copyright © 2012 John Wiley & Sons, Ltd.

Novel Chiral Bifunctional L‐Thiazoline‐Thiourea Derivatives: Design and Application in EnantioselectiveMichael Reactions

“…We recently first reported the design, synthesis, and application of a series of novel modular, thiazoline‐containing N‐O ligands 6 derived from L‐cysteine (Scheme ) in asymmetric addition of diethylzinc to aromatic aldehydes . Encouraged by these successful efforts and aiming to demonstrate the generality of the new catalysts containing thiazoline, we fixed our attention on employing these novel catalysts 13 (Scheme ) by tuning the thiourea moiety for enantioselective addition of 1, 3‐dicarbonyl compounds onto β ‐nitrostyrenes.…”

“…( R )‐tetrahydrothiazo‐2‐thione‐4‐carboxylic acid [( R )‐TTCA] 2 was synthesized by known methods, m.p. = 179–181 °C, [α] = −86.3 ( c 1.2, 0.5 N HCl).…”

Asymmetric Synthesis of 2,4,5‐Trisubstituted Δ2‐Thiazolines

“…As ligands, they have proven successful in a variety of reactions, including Pd-catalyzed allylic substitutions, [5a, 6] Diels-Alder reactions, [7] Friedel-Crafts alkylations of indoles [8] and alkylzinc additions to aldehydes. [9] Many ways to construct the D 2 -thiazoline heterocycles have been developed, and they normally involve the use of a dehydrating reagent. Among the known methods are reactions with triethylamine (TEA)/MsCl (Ms = mesityl), [5a, 6] SOCl 2 /pyridine, [10] the Lawesson reagent, [7b, 11] the Burgess reagent, [4c, 10] the Hendrickson reagent, [12] TiCl 4 , [13] PCl 5 , [4a] P 2 S 5 , [14] diethylaminosulfur trifluoride (DAST), [15] [bis(2-methoxyethyl)amino]sulfur trifluoride (Deoxo-Fluor), [9a, 16] PPh 3 /diisopropyl azodicharboxylate (DIAD), [17] 3-nitrophenylboronic acid, [18] and Ru/tert-butyl hydroperoxide (TBHP).…”