Abstract
An enantioselective N-heterocyclic carbene catalysed formal [3+2] cycloaddition has been developed for the synthesis of oxazolindin-4-one products. The reaction of oxaziridines and α-aroyloxyaldehydes under N-heterocyclic carbene catalysis provides the formal cycloaddition products with excellent control of the diastereo- and enantioselectivity (12 examples, up to >95:5 dr, >99:1 er). A matched-mismatched effect between the enantiomer of the catalyst and oxaziridine was identified, and preliminary mechanistic studies have allowed the proposal of a model to explain these observations.
Highlights
Beyond the classical acyl anion equivalent reactivity mode, the development of N-Heterocyclic carbenes (NHCs) catalysis has resulted in numerous methods that proceed by acyl azolium, a,b-unsaturated acyl azolium, azolium enolate, homoenolate and radical cation intermediates
Azolium enolate species have been generated from the direct addition of NHCs to ketenes,6b,c the inherent difficulties associated with substrate synthesis and stability has resulted in the development of alternative methods
In previous work we introduced the use of a-aroyloxyaldehydes in NHC redox catalysis
Summary
N-Heterocyclic carbenes (NHCs) occupy a privileged position within the field of Lewis base organocatalysis due to the wide range of reactive intermediates accessible from readily available starting materials. Beyond the classical acyl anion equivalent reactivity mode, the development of NHC catalysis has resulted in numerous methods that proceed by acyl azolium, a,b-unsaturated acyl azolium, azolium enolate, homoenolate and radical cation intermediates. Within this field, azolium enolates have been applied to a range of reactions, including highly enantio- and diastereoselective intramolecular cyclizations, desymmetrizations, and (formal) [4 +2],5 [2+2],6 and to a lesser extent [3+2] cycloadditions. Traditionally, azolium enolate species have been generated from the direct addition of NHCs to ketenes,6b,c the inherent difficulties associated with substrate synthesis and stability has resulted in the development of alternative methods. The most common approach to azolium enolate intermediates is through the use of NHC redox catalysis, in which a-functionalized aldehydes (such as a-haloaldehydes, a-aryloxyaldehydes or epoxyaldehydes) or enals are used. By using 2 equivalents of racemic oxaziridine an efficient kinetic resolution of the oxaziridine was realized, with selectivity factors of up to 52 being reported.14 Building upon these precedents, the expansion of the range of methods available for the generation of enantioenriched oxazolidin-4-one products is investigated through the use of aaroyloxyaldehydes as bench-stable azolium enolate precursors in NHC redox catalysis (Scheme 2, c). The expansion of the range of methods available for the generation of enantioenriched oxazolidin-4-one products is investigated through the use of aaroyloxyaldehydes as bench-stable azolium enolate precursors in NHC redox catalysis (Scheme 2, c) This approach allows access to anti-5-alkyl-oxazolidin-4-one products, previously inaccessible in enantioenriched form using organocatalytic methods
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
