Zinc‐Catalyzed Alkyne Oxidation/CH Functionalization: Highly Site‐Selective Synthesis of Versatile Isoquinolones and β‐Carbolines

Abstract

An efficient zinc(II)-catalyzed alkyne oxidation/C-H functionalization sequence was developed, thus leading to highly site-selective synthesis of a variety of isoquinolones and β-carbolines. Importantly, in contrast to the well-established gold-catalyzed intermolecular alkyne oxidation, over-oxidation can be completely suppressed in this system and the reaction most likely proceeds by a Friedel-Crafts-type pathway. Mechanistic studies and theoretical calculations are described.

Copper‐Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza‐[n.2.1] Skeletons

“…[17,18] Gratifyingly,s ubsequent studies revealed that copper catalysts could catalyze the cascade cyclization smoothly (entries 8-11), and 2a was fromed in 85 %y ield by employing CuOTf as the catalyst (entry 9). Further screening of solvents such as toluene and chlorobenzene led to as lightly decreased yield (entries [14][15]. Transition-metal-catalyzed cycloisomerization-initiated tandem reactions for the synthesis of bridged scaffolds.…”

“…By utilizing the steric strain in ring formation to achieve anti-Markovnikov regioselectivity,o ur group has developed several gold-catalyzed 5-endo-dig hydroamination-initiated tandem reactions,a ffording valuable five-membered N-heterocycles. [14] Herein, we describe the realization of unprecedented copper-catalyzed cascade cyclization of indolyl homopropargyl amides, [15] allowing the practical and atom-economical synthesis of ad iverse array of valuable bridged aza-[n.2.1] skeletons (n = 3-6) with excellent diastereoselectivity and enantioselectivity by achirality-transfer strategy.F urthermore,amechanistic rationale for this serial cascade cyclization is strongly supported by av ariety of control experiments,a nd importantly,i ts mechanism is distinctively different from the related gold catalysis. [13] However,a chieving this cascade reaction is highly challenging:1 )how do we prevent the competing exo cyclization of the terminal alkyne partner by the highly nucleophilic indole moiety by at ypical Markovnikov addition; [5] and 2) how do we achieve the desired cascade cyclization but not stop at the dihydropyrrole intermediate.…”

The Fascinating Chemistry of α‐Haloamides

“…Ts‐ or Ms‐protected ynamides underwent Lewis acid‐catalyzed transformation into α‐halo amides through an alkyne oxidation‐halogenation tandem process with 2‐halopyridine N ‐oxide (2 equiv.) serving both as the oxidant and the halogen source (Scheme ) –…”

(Imidazol‐2‐yl)methyl‐1,3‐propanediones: Regioselective C–H Functionalization of the Imidazole Ring by Acylacetylene/Aldehyde Pairs

“…Examples include the gold-catalyzed annulation of nitroalkynes with indoles, [9] iridium-photocatalyst-promoted decarboxylative alkynylation of carboxylic acids, [10] gold-catalyzed rearrangement of O-propargylic formaldoximes, [11] iron-assisted cycloaddition reaction of diynes with phosphaalkynes, [12] gold-catalyzed cyclization of 2-alkynyl-N-propargylanilines, [13] alkyne oxidation/C-H functionalization under the action of Zn(OTf ) 2 , [14] rhodium-catalyzed cycloadditions of alkynes with cyclopropylideneacetamides, [15] sunlightdriven decarboxylative alkynylation of α-keto acids with bromoacetylenes, [16] copper-initiated trifluoromethylazidation of alkynes, [17] synthesis of chiral allenoates through the asymmetric C-H insertion of α-diazo esters into terminal alkynes with the help of copper compounds, [18] and Pd-catalyzed cross-coupling of terminal alkynes with ene-yne-ketones. Examples include the gold-catalyzed annulation of nitroalkynes with indoles, [9] iridium-photocatalyst-promoted decarboxylative alkynylation of carboxylic acids, [10] gold-catalyzed rearrangement of O-propargylic formaldoximes, [11] iron-assisted cycloaddition reaction of diynes with phosphaalkynes, [12] gold-catalyzed cyclization of 2-alkynyl-N-propargylanilines, [13] alkyne oxidation/C-H functionalization under the action of Zn(OTf ) 2 , [14] rhodium-catalyzed cycloadditions of alkynes with cyclopropylideneacetamides, [15] sunlightdriven decarboxylative alkynylation of α-keto acids with bromoacetylenes, [16] copper-initiated trifluoromethylazidation of alkynes, [17] synthesis of chiral allenoates through the asymmetric C-H insertion of α-diazo esters into terminal alkynes with the help of copper compounds, [18] and Pd-catalyzed cross-coupling of terminal alkynes with ene-yne-ketones.…”