Catalytic Asymmetric Aziridination of α,β‐Unsaturated Aldehydes

Abstract

The development, scope, and application of the highly enantioselective organocatalytic aziridination of α,β-unsaturated aldehydes is presented. The aminocatalytic azirdination of α,β-unsaturated aldehydes enables the asymmetric formation of β-formyl aziridines with up to >19:1 d.r. and 99% ee. The aminocatalytic aziridination of α-monosubstituted enals gives access to terminal α-substituted-α-formyl aziridines in high yields and up to 99% ee. In the case of the organocatalytic aziridination of disubstituted α,β-unsaturated aldehydes, the transformations were highly diastereo- and enantioselective and give nearly enantiomerically pure β-formyl-functionalized aziridine products (99% ee). A highly enantioselective one-pot cascade sequence based on the combination of asymmetric amine and N-heterocyclic carbene catalysis (AHCC) is also disclosed. This one-pot three-component co-catalytic transformation between α,β-unsaturated aldehydes, hydroxylamine derivatives, and alcohols gives the corresponding N-tert-butoxycarbonyl and N-carbobenzyloxy-protected β-amino acid esters with ee values ranging from 92-99%. The mechanisms and stereochemistry of all these catalytic transformations are also discussed.

The effect of the N-mesityl group in NHC-catalyzed reactions

“…Indeed, Rovis very recently reported an elegant enantioselective intermolecular Stetter reaction between α,β -unsaturated aldehydes and nitroalkenes using a chiral analog of 2 . 21b The N -C 6 F 5 triazolium catalyst is also preferred for redox esterification reactions of α -heteroatomic and α,β -epoxy aldehydes 26 . These reactions do not require formation of the Breslow intermediate (Figure 2), 1a,27 and catalyst turnover is most likely the turnover-limitng step – a process facilitated by more electron deficient carbenes, which are better leaving groups.…”

Combined heterogeneous metal/organic catalysts for eco-friendly synthesis

“…Moreover, starting the ARC sequence with ent-4 as the catalyst and 1m as the allylic alcohol afforded ent-13m in high yield, dr and er. Future investigations would include kinetic resolution of racemic compounds 10 by the chiral amine 4 catalyzed azirdinarion transformation [62,63].…”

“…Thus, the palladium (0)-aminopropyl-mesocellular foam (Pd(0)-AmP-MCF)-catalyzed aerobic oxidation [31] of alcohols 1 was linked in sequence with several chiral amine 4 [61]-catalyzed one-pot cascade transformations and provided a variety of functional molecules (e.g., aziridine 3a [62,63], E-6b [64,65], pyrrolidine 7a [66] and 8d [67]) with high enantiomeric ratios (Scheme 2). Next, these compounds such as E-6b and 8d can be rapidly converted to tropane alkaloids (e.g., cocaine) [64,65] and secologanine tryptamine alkaloids [67], respectively (Scheme 2b and 2d).…”

Evolution of asymmetric organocatalysis: multi- and retrocatalysis

“…81 Similarly to Jørgensen's work, the use of (S)-7 and 119 as catalysts afforded various β-amino acid ester derivatives 141 in moderate to good yields (up to 80% yield) with 92-99% ee. When aromatic enals such as 91 or 115 were used the corresponding products were obtained with significantly lower yield (25-54% yield) although with excellent stereoselectivities (94-99% ee) due to a base-catalyzed rearrangement sidereaction.…”