A synthetic method to prepare 1,2‐diamines efficiently that relies on the 4CzPN‐catalysed α‐aminoalkylation of azomethine imines by secondary and tertiary α‐silylamines under blue light emitting ...diode (LED) light (456 nm) is described. Achieved under metal‐ and additive‐free reaction conditions at room temperature, the synthetic protocol was shown to afford product yields up to 99% and applicable to the late‐stage functionalisation of three drug molecules and the gramme‐scale preparation of one example.
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•The reactivity of isatin N, N′-cyclic azomethine imine as a new synthon for 1,3-dipolar cycloaddition has been discussed.•Synthesized diverse five- or six-membered ring fused ...spirooxindoles linked through the spiro carbon at the C3-position.•Synthesis of dinitrogen-containing spirobicyclic compounds.•Abnormal CNC and normal CNN reactivity were covered.
Spirooxindoles are frequently encountered in the basic skeleton of a diverse range of natural alkaloids and therapeutically significant molecules. Consequently, the developments of elegant synthetic methods for the assembly of these motifs are extremely demanding but challenging. On the other hand, the utilization of isatin N, N′-cyclic azomethine imines which is a new type of stable azomethine imines, in 1,3-dipolar cycloaddition, Michael addition and α-alkylation reaction for the preparation of carbon–carbon, and structurally functionalized heterocyclic compounds have been studied but still underdeveloped. In this digest, the developments achieved regarding the construction of spirooxindoles mediated by isatin N, N′-cyclic azomethine imines have been disclosed.
A diastereoselective (3+3) cycloaddition of azomethine imines and in situ‐generated azaoxyallyl cations from α‐halohydroxamate promoted by a Brønsted base has been developed. A series of pyrazolo ...1,2‐a1,2,4triazin‐6‐ones were accessed with up to 95% yields and diastereoselectivities greater than 20:1. The asymmetric version of this reaction was explored and moderate enantioselectivity was achieved after screening a series of cinchonine‐derived chiral catalysts.
We have developed a synthetic strategy for Et3N‐promoted 5+3 cycloaddition reactions between acetoxypyranones and azomethine imines to access functionalized azabicyclo3.3.1alkenones with three ...tertiary stereocenters (31 examples, 36% to 87% yield, 5.5:1 to >20:1 dr). The method was scalable, and the products could be transformed to various eight‐membered‐ring bridged heterocyclic molecules.
Abstract
A cross‐1,3‐dipolar cycloaddition reaction of
α
‐halohydroxamates (in situ generated azaoxyallyl cations) with
N,N′
‐cyclic azomethine imines was developed. The synthetic protocol provided ...facile and rapid access to pyrazolo1,2‐
a
1,2,4triazine derivatives in good yields and excellent diastereoselectivities under mild metal‐free conditions.
Catalytic asymmetric 3+2 cycloadditions of C,N‐cyclic azomethine imines with δ‐substituted allenoates have been developed in the presence of (S)‐Me‐f‐KetalPhos, affording functionalized ...tetrahydroquinoline frameworks in good yields with high diastereo‐ and good enantioselectivities under mild condition. The substrate scope has been also examined. This is the first time that δ‐substituted allenoates have been applied as a δ,γ‐CC bond participated C2 synthon in asymmetric synthesis.
Another round: Catalytic asymmetric 3+2 cycloaddition of C,N‐cyclic azomethine imines with δ‐substituted allenoates have been developed in the presence of (S)‐Me‐f‐KetalPhos, affording functionalized tetrahydroquinoline frameworks in good yields with high diastereo‐ and good enantioselectivities under mild conditions. This is the first example applying δ‐substituted allenoates as C2 synthons in asymmetric δ,γ‐CC bond formation.
A practical and mild approach to prepare tetrahydropyrazolo1,2‐a‐pyrazole‐1,7‐diones, bearing up to three stereocentres, by reacting ready available N,N′‐cyclic azomethine imines and pyrazoleamides ...under catalytic loading of commercial 1,5,7‐triazabicyclo4.4.0dec‐5‐ene (TBD), has been developed. The products are obtained in good yields and high diastereoselectivity, working at room temperature. Preliminary bioassay showed the products to inhibit growth of Gram‐positive bacteria.
The more dipoles, the merrier: An asymmetric 3+3 cycloaddition of azomethine ylides derived from imines 1 with azomethine imines 2 in the presence of a chiral ferrocenylphosphine–copper catalyst ...afforded highly functionalized heterocyclic products 3 in high yield with excellent enantio‐ and diastereoselectivity (see scheme; DBU=1,8‐diazabicyclo5.4.0undec‐7‐ene). The 1,3‐dipolar reaction partners can be readily prepared from aldehydes.
A non‐catalytic, mild, and easy‐to‐handle protecting group switched 1,3‐dipolar cycloaddition (1,3‐DC) between bi‐ or mono‐N‐protected Dha and C,N‐cyclic azomethine imines, which afford various ...quaternary amino acids with diverse scaffolds, is disclosed. Specifically, normal‐electron‐demand 1,3‐DC reaction occurs between bi‐N‐protected Dha and C,N‐cyclic azomethine imines, while inverse‐electron‐demand 1,3‐DC reaction occurs between mono‐N‐protected Dha and C,N‐cyclic azomethine imines. Above all, the reactions can be carried out between peptides with Dha residues at the position of interest and C,N‐cyclic azomethine imines, both in homogeneous phase and on resins in SPPS. It provides a new toolkit for late‐stage peptide modification, labeling, and peptide–drug conjugation. To shed light on the high regioselectivity of the reaction, DFT calculations were carried out, which were qualitatively consistent with the experimental observations.
A non‐catalytic, mild, and easy‐to‐handle protecting group switching normal‐electron‐demand or inverse‐electron‐demand 1,3‐dipolar cycloaddition between bi‐ or mono‐N‐protected Dha and C,N‐cyclic azomethine imines is disclosed and applied in the late‐stage peptide modification, labeling, and peptide–drug conjugation.
