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The full scope and limitations of the catalytic acylative kinetic resolution of a range of tertiary heterocyclic alcohols (78 examples, s up to >200) is reported under operationally‐simple conditions, using low loadings of a commercially available Lewis basic isothiourea catalyst, HyperBTM (generally 1 mol %). The protocol is highly effective for the kinetic resolution of 3‐substituted 3‐hydroxyoxindole and α‐substituted α‐hydroxylactam derivatives bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. The full power of this methodology has been showcased through the synthesis of highly enantioenriched biologically‐active target compounds in both enantiomeric forms. To provide further insight into the reaction mechanism, a detailed kinetic analysis of this Lewis base‐catalyzed acylation of tertiary alcohols is reported using the variable time normalization analysis (VTNA) method. [ABSTRACT FROM AUTHOR]

Abstract: A combination of experimental and computational studies have identified a C=O⋅⋅⋅isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea‐catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions. [ABSTRACT FROM AUTHOR]

The non-enzymatic acylative kinetic resolution of challenging aryl-alkenyl (sp2 vs. sp2) substituted secondary alcohols is described, with effective enantiodiscrimination achieved using the isothiourea organocatalyst HyperBTM (1 mol %) and isobutyric anhydride. The kinetic resolution of a wide range of aryl-alkenyl substituted alcohols has been evaluated, with either electron-rich or naphthyl aryl substituents in combination with an unsubstituted vinyl substituent providing the highest selectivity ( S=2-1980). The use of this protocol for the gram-scale (2.5 g) kinetic resolution of a model aryl-vinyl (sp2 vs. sp2) substituted secondary alcohol is demonstrated, giving access to >1 g of each of the product enantiomers both in 99:1 e.r. [ABSTRACT FROM AUTHOR]

N-Acyl imidazoles and catalytic isothiourea hydrochloride salts function as ammonium enolate precursors in the absence of base. Enantioselective Michael addition-cyclization reactions using different α,β-unsaturated Michael acceptors have been performed to form dihydropyranones and dihydropyridinones with high stereoselectivity. Detailed mechanistic studies using RPKA have revealed the importance of the 'imidazolium' effect in ammonium enolate formation and have highlighted key differences with traditional base-mediated processes. [ABSTRACT FROM AUTHOR]

A highly enantioselective Lewis base-catalysed formal [3+2] cycloaddition of ammonium enolates and oxaziridines to give stereodefined oxazolidin-4-ones in high yield is described. Employing an enantioenriched oxaziridine in this process leads to a matched/mis-matched effect with the isothiourea catalyst and allowed the synthesis of either syn- or anti-stereodefined oxazolidin-4-ones in high d.r., yield and ee. Additionally, the oxazolidin-4-one products have been derivatised to afford functionalised enantioenriched building blocks. [ABSTRACT FROM AUTHOR]

Rate and equilibrium constants for the reaction between N-aryl triazolium N-heterocyclic carbene (NHC) precatalysts and substituted benzaldehyde derivatives to form 3-(hydroxybenzyl)azolium adducts under both catalytic and stoichiometric conditions have been measured. Kinetic analysis and reaction profile fitting of both the forward and reverse reactions, plus onwards reaction to the Breslow intermediate, demonstrate the remarkable effect of the benzaldehyde 2-substituent in these reactions and provide insight into the chemoselectivity of cross-benzoin reactions. [ABSTRACT FROM AUTHOR]

A stereodivergent asymmetric Lewis base catalyzed Michael addition/lactonization of enone acids into substituted dihydrobenzofuran and tetrahydrofuran derivatives is reported. Commercially available ( S)-(−)-tetramisole hydrochloride gives products with high syn diastereoselectivity in excellent enantioselectivity (up to 99:1 d.r. syn/ anti, 99 % ee syn), whereas using a cinchona alkaloid derived catalyst gives the corresponding anti-diastereoisomers as the major product (up to 10:90 d.r. syn/ anti, 99 % ee anti). [ABSTRACT FROM AUTHOR]

Hetero-Diels-Alder reactions of trichloromethyl α-enones as unsaturated amide and ester equivalents with azolium enolates, generated from α-aroyloxy aldehydes yield syn-dihydropyranones, which are isolated or transformed into diamides diastereo- and enantioselectively by in situ ring-opening with amines and subsequent aminolysis. [ABSTRACT FROM AUTHOR]

The NHC-catalyzed reaction of aldehydes (I) with N-aryl-N-aroyldiazenes gives α-hydrazino esters with high enantioselectivities. [ABSTRACT FROM AUTHOR]

In the presence of the chiral chloride (NHC), α-aroyloxyaldehydes undergo stereoselective cyclization with (E)- and (Z)-trifluoromethyl enones to afford syn- and anti-dihydropyranones. [ABSTRACT FROM AUTHOR]

Hydrazone-carboxylic acids undergo intramolecular cyclization in the presence of pivaloyl chloride, iPr2NEt, and catalytic DABCO to form a range of substituted fused tricyclic 2,3-dihydro-1,3,4-oxadiazoles in high yields. [ABSTRACT FROM AUTHOR]

Using (2S,3R)-2-phenyl-3-isopropyl-2,3-dihydrobenzthiazolo[3,2-a]pyrimidine (BTP) as chiral catalyst, 2,3-disubstituted dimethyl pentanedioates (IV) and (VI) could be obtained in high diastereo- and enantioselectivity. [ABSTRACT FROM AUTHOR]

The reaction tolerates various hydrazone-carboxylic acid based substrates, and depending on the functional groups present the products are obtained in moderate to very high yields. [ABSTRACT FROM AUTHOR]

Tetramisole‐mediated reaction of 2‐substituted acetic acids (I) and (IV) and α,β‐unsaturated ketimines (II) gives the title compounds in good to high yields and with excellent stereoselectivities. [ABSTRACT FROM AUTHOR]