Azide-alkyne cycloadditions, asymmetric

Apart from the utilization of aryl- and vinyl-diazoacetates that can achieve the moderate to high chemo-, regio-, and enantioselectivity in intermolecular asymmetric C—H bond insertion reactions, Af-sulfonyl-l,2,3-triazole 11 was found to be able to function as an alternative carbene precursor for diverse transformations (Scheme 1.4). One advantage for using the N-sulfonyl-1,2,3-triazole is that it could be easily prepared by the Cu -catalyzed azide-alkyne cycloaddition (CuAAC) reaction, and in some cases, delicately designed reactions can be conducted in a one-pot procedure starting from alkynes and sulfonyl azides. Moreover, since there exists an inherent equilibrium... 

Acylations Carbon-coated magnetic Co-nanoparticles tagged with azabis (oxazoline)-Cu(II) complexes were utilized in a Cu(I)-catalyzed azide/alkyne cycloaddition (CuAAC), and the efficacy of the resulting nanomagnetic catalyst was tested in the kinetic resolution (KR) of racemic l,2-diphenylethane-l,2-diol via asymmetric monobenzoylation under batch conditions and in a continuous flow-type reactor [39]. 

Scheme 36 Asymmetric azide-alkyne cycloaddition via desymmetrization of oxindole-based 1,6-heptadiynes...

Scheme 37 Asymmetric azide-alkyne cycloaddition of dialkynes bearing prochiral biaryl groups...

Ligand addition to the CuAAC reaction can affect kinetic resolution by using chiral precursors and ligands. The first example for asymmetric kinetic resolution of the azide-alkyne cycloaddition was given by Fokin and Finn, who tested several copper complexes of the bis(oxazolinyl)pyridine (pybox) family in combination with the racemic mixture of the compound 25 (Scheme 9.3). " Kinetic resolution could be observed up to a maximum enantiomer selectivity factor of three using ligand 18. 

Brittain WDG, Buckley BR, Fossey IS (2016) Asymmetric copper-catalyzed azide-alkyne cycloadditions. ACS Catal 6(6) 3629-3636... 

In the mechanism of the CuAAC reaction described above, the metal catalyst activates terminal alkyne for reaction with a Cu-coordinated azide. This mode of reactivity operates with other dipolar reagents as well. In fact, the first example of a copper-catalzyed 1,3-dipolar cycloaddition reaction of alkynes was reported for nitriones by Kinugasa in 1972 [124]. An asymmetric version of the Kinugasa reaction was developed by Fu et al. in 2002 [125, 126]. 

High enantioselectivites in the aza-Michael reaction have been achieved using alternate organocatalysts, and the addition of benzotriazole to nitroolefins occurs with up to 94% ee using bifimctional catalysts such as (11.64). Guerin and Miller have developed an alternate approach to the enantioselective introduction of triazoles based on the asymmetric conjugate addition of azide followed by a 1,3-dipolar cycloaddition of the product with an alkyne. In this approach, the addition of hydrazoic acid to Michael acceptors such as (11.133) proceeds with good ee in the presence of the dipeptide (11.134). ... 

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