Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

Abstract

Copper-catalysed asymmetric C–C bond-forming reactions using organometallic reagents have developed into a powerful tool for the synthesis of complex molecules with single or multiple stereogenic centres over the past decades. Among the various acceptors employed in such reactions, those with a heterocyclic core are of particular importance because of the frequent occurrence of heterocyclic scaffolds in the structures of chiral natural products and bioactive molecules. Hence, this review focuses on the progress made over the past 20 years for heterocyclic acceptors.

Asymmetric Tandem Conjugate Addition and Reaction with Carbocations on Unsaturated Heterocycles

“…Conceptually, conjugate additions to heterocyclic Michael acceptors stem from extensive research in the field of asymmetric conjugate additions [9] . Different reactivity profiles such as lower electrophilicity at the β‐position (C‐3) or compatibility issues due to the presence of additional functionalities pose additional restraints on ACA of organometallic reagents to heterocyclic systems [10] . Among the earliest examples of ACAs to heterocyclic Michael acceptors were additions of dialkyl zinc reagents to unsaturated lactams, [11] and lactones, furanones, and pyranones developed by Hoveyda [12] .…”

“…[9] Different reactivity profiles such as lower electrophilicity at the β-position (C-3) or compatibility issues due to the presence of additional functionalities pose additional restraints on ACA of organometallic reagents to heterocyclic systems. [10] Among the earliest examples of ACAs to heterocyclic Michael acceptors were additions of dialkyl zinc reagents to unsaturated lactams, [11] and lactones, furanones, and pyranones developed by Hoveyda. [12] Feringa, Dieter as well as our laboratory have developed methodologies for Cu-catalyzed asymmetric conjugate additions to N-protected piperidones using dialkylzinc [13] and alkylzirconium reagents.…”

Ruthenium catalyzed β-selective alkylation of vinylpyridines with aldehydes/ketonesviaN2H4mediated deoxygenative couplings

“… 1 The post-elaboration of this privileged scaffold continues to play a vital role to rapidly assemble related functionalized N-containing heterocycles and new molecular architectures. 2 To this end, vinyl pyridines have been well adopted as versatile synthons 3 in terms of their electrophilic nature, especially in analogous Michael-type additions with external nucleophiles, such as Grignard reagents 4 or boronic acids. 5 In contrast, the reductive couplings 6 of vinyl pyridines with another electrophile have been less explored and remained a challenging study.…”

Cu(I)-Catalyzed Alkynylation of Quinolones

“…At the start of this work, the optimization studies were carried out for the alkynylation reaction between Cbz-protected quinolone 1a and phenylacetylene 2a in the presence of base DIPEA and catalytic amounts of Cu­(I) salt. On the basis of our group’s experience with Lewis-acid-promoted Cu­(I)-catalyzed conjugate additions, ,− we evaluated the effect of several Lewis acids to enhance the electrophilicity of the quinolone substrate 1a . Excellent conversion to the desired addition product 3a was observed in the presence of a stoichiometric amount of tert -butyldimethylsilyl triflate (TBDMSOTf) after stirring overnight (Table , entry 1).…”