Asymmetric Isothiourea-Catalysed Formal [3+2] Cycloadditions of Ammonium Enolates with Oxaziridines.

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.

Organocatalytic Michael addition-lactonisation of carboxylic acids using α,ß-unsaturated trichloromethyl ketones as α,ß-unsaturated ester equivalents.

Isothiourea HBTM-2.1 catalyses the Michael addition-lactonisation of 2-aryl and 2-alkenylacetic acids and α,ß-unsaturated trichloromethyl ketones. Ring-opening of the resulting dihydropyranones and subsequent alcoholysis of the CCl3 ketone with an excess of methanol gives a range of diesters in high diastereo- and enantioselectivity (up to 95 : 5 dr and >99% ee). Sequential addition of two different nucleophiles to a dihydropyranone gives the corresponding differentially substituted diacid derivative.

α-Ketophosphonates as ester surrogates: isothiourea-catalyzed asymmetric diester and lactone synthesis.

Isothiourea HBTM-2.1 catalyzes the asymmetric Michael addition/lactonization of aryl- and alkenylacetic acids using α-keto-ß,γ-unsaturated phosphonates as α,ß-unsaturated ester surrogates, giving access to a diverse range of stereodefined lactones or enantioenriched functionalized diesters upon ring-opening.

Isothiourea-catalyzed asymmetric synthesis of ß-lactams and ß-amino esters from arylacetic acid derivatives and N-sulfonylaldimines.

The isothiourea HBTM-2.1 (5 mol %) catalyzes the asymmetric formal [2 + 2] cycloaddition of both arylacetic acids (following activation with tosyl chloride) and preformed 2-arylacetic anhydrides with N-sulfonylaldimines, generating stereodefined 2,3-diaryl-ß-amino esters (after ring-opening) and 3,4-diaryl-anti-ß-lactams, respectively, with high diastereocontrol (up to >95:5 dr) and good to excellent enantiocontrol. Deprotection of the N-tosyl substituent within the ß-lactam framework was possible without racemization by treatment with SmI2.