Catalytic Asymmetric Reactions with N,O-Aminals

Abstract

N,O-aminals, molecules bearing a geminally N,O-substituted (stereogenic) carbon center, have been recently recognized as an important class of building blocks in organic synthesis. As direct precursors of imines and iminium ions, N,O-aminals were converted through asymmetric organocatalysis or metal catalysis to diverse enantiomerically enriched compounds including N-heterocycles. Furthermore, cyclic N,O-hemiaminals acted as acyclic amino aldehyde surrogates, which were transformed to enantioenriched products otherwise challenging to access. Finally, cyclic N,O-aminals were formed in situ as key intermediates in asymmetric catalysis. In this review, we introduce a wide array of catalytic asymmetric protocols involving the use of four distinct types of N,O-aminals as starting materials or key intermediates.

Controlling Regioselectivity in the Enantioselective N‐Alkylation of Indole Analogues Catalyzed by Dinuclear Zinc‐ProPhenol

“…Also there are many methods available for the synthesis of N,O -aminals and utilized for several organic transformations. 12 On the other hand, attempts to develop more traditional indole moieties containing asymmetric aminal syntheses as shown in eq. 2 have been less effective.…”

Direct enantioselective vinylogous Mannich‐type reactions of acyclic enals: New experimental insights into the E/Z‐dilemma

“…In principle, a vinylogous extension of recently reported enantioselective α‐alkylations of aldehydes with N‐acyl quinolinium ions poses several reactivity and selectivity issues . In fact, there are several regioselectivity issues about the nucleophilic addition (α‐selectivity vs γ‐selectivity) of the in situ formed dienamine to the reactive positions of the N‐acylquinolinium ion (α′‐selectivity vs γ′‐ selectivity) (Figure ) .…”

Carbene‐Catalyzed Enantioselective Aromatic N‐Nucleophilic Addition of Heteroarenes to Ketones

“…For example, the nitrogen atoms of indole molecules can undergo addition reactions with reactive ketones to form N , O ‐acetals . Acetals are versatile structural motifs with applications in organic synthesis and pharmaceutical research . Most acetal‐forming reactions can be made very efficient.…”

“…Heteroarenes are privileged structures with al arge presence in medicines,p esticides,l igands,n atural products,a nd other functional molecules.The heteroatoms in some of these aryl molecules,s uch as indoles and pyrroles,c an serve as convenient handles for structural modifications and alternations of functionality.F or example,t he nitrogen atoms of indole molecules can undergo addition reactions with reactive ketones to form N,O-acetals. [1,2] Acetals are versatile structural motifs with applications in organic synthesis [3,4] and pharmaceutical research. [5][6][7][8][9] Most acetal-forming reactions can be made very efficient.…”