Highly diastereoselective synthesis of 2,3-dihydro-9bH- thiazolo[2,3-a]isoindolin-5-ones

Abstract

Condensation of 2-acetyl benzoic acid with aminothiols proceeds with extremely high diastereoselectivity to produce the desired 2,3-dihydro-9bH-thiazolo[2,3-a]isoindolin-5-one products in good yield. The relative stereochemistry of the major diastereoisomer, formed exclusively when using non-racemic aminothiol substrates, has been determined for the first time by single crystal X-ray analysis.

2,3-Dihydroferroceno[3,4]pyrrolo[2,1-b]thiazol-5(8b)-ones: Synthesis, Structure and DFT Study on the Mechanism of Chemo- and Diastereoslective Annulations of (Sp)-2-Formylferrocenecarbonyl Fluoride and (Sp)-2-Formylferrocenecarboxylic Acid

“…First, we attempted to perform the annulation reactions of 2-formylferrocene carboxylic acid ( Scheme 1 ) with cysteamine and enantiomeric cysteine methyl esters [ 3 , (D)- 6 and (L)- 6 , Scheme 1 a] under three documented conditions [ 31 , 32 , 33 ] successfully applied to the related condensations of 2-formyl- or acylbenzoic acids constructing heterocycles with a 2,3-dihydrothiazolo-[2,3-a]isoindol-5(9bH)-one skeleton; however, these efforts remained in vain, but allowed us to collect the following findings: (i) heating the coupling components under harsh conditions provided by reflux in toluene in the presence of a catalytic amount of toluenesulfonic acid or in xylene, as reported by Mertens et al [ 31 ] and Allin et al [ 32 ], respectively, led to the formation of undefined tarry materials even under argon atmosphere as the probable consequence of a substantially decreased thermal and oxidative stability of the organometallic precursor; (ii) when the mixture of 1 and the hydrochlorid salt of any of the aforementioned mercaptoamine components was stirred in EtOH-water (1:1) at room temperature in the presence of potassium hydrogen carbonate, representing the mild conditions described by Pinho e Melo [ 33 ], mixtures of hardly separable interconverting imine- and thiazolidinyl-substituted ferrocene carboxylates were formed as detected by 1 H-NMR in the evaporated organic (CH 2 Cl 2 ) extracts of the reaction mixtures, referring to the resistance of the carboxyl group to participate in lactame-forming cyclisation. Since it has been disclosed in our previous research that ( S p )-2-formylferrocenoylfluoride 2 , readily accessible from 1 ( Scheme 1 a), can be used as an easy-to-handle yet reactive bis-electrophilic coupling partner in ferroceno[f]pyridazinone-yielding heterocyclisations proceeding via lactame formation [ 17 ], we first envisaged testing this reagent as a coupling component in our experiments aimed at the synthesis of the targeted ferroceno[3,4]pyrrolo[2,1-b]thiazol-5(8bH)-ones ( Scheme 1 a).…”