ABSTRACT
A halogen-atom transfer (XAT) strategy utilizing α-aminoalkyl radicals allows the generation of aryl radicals at room temperature, which is applied for intramolecular cyclization reactions en route to biologically relevant alkaloids. Starting from simple halogen-substituted benzamides under visible light irradiation in the presence of an organophotocatalyst (4CzIPN) and nBu3N allows the modular construction of the phenanthridinone core, which gives facile access to drug analogs and alkaloids, e.g., from the Amaryllidaceae family. The reaction pathway most likely involves a quantum mechanical tunneling enabled transfer event to achieve aromatization-halogen-atom transfer.
ABSTRACT
The nucleophilic reactivity of α,α-difluorinated gem-diols toward activated pyridinium salts has been capitalized in a highly regioselective fashion, offering biologically relevant 1,4-dihydropyridines and 3,4-dihydro-2-pyridones adorned with the valuable gem-difluoromethylene motif. The protocol is scalable as well as high yielding and accommodates a broad range of substrates and functional groups. Additionally, the synthesis of difluorinated oxa-azabicyclo[3.3.1]nonane frameworks has been showcased through product diversification.
Subject(s)
Dihydropyridines , Pyridines , Molecular StructureABSTRACT
A vinylogy concept driven annulation strategy is developed to access [4,4]-carbospirocycles from alkylidene malononitriles and cyclopentene-1,3-diones. The reaction is catalyzed by an inexpensive organocatalyst and products with three stereocenters were obtained as a single diastereomer in high yields. The spiro-selectivity originates from the reaction of the thermodynamic enolate intermediate which is fundamentally intriguing.
ABSTRACT
An unprecedented regiodivergent nitrosocarbonyl aldol reaction of γ-substituted deconjugated butenolides is described. While Lewis base catalyst quinidine leveraged O-selective nitrosocarbonyl aldol reaction exclusively at the γ-position of deconjugated butenolides to produce γ-aminoxylation products, Lewis acid catalyst Cu(OTf)2 steered the competitive N-selective nitrosocarbonyl aldol reaction at the ß-position, resulting in heterodifunctionalized butenolides. Both processes were amenable to a broad range of substrates and scalable, while the latter one represents a rare example of one-pot hetero-ß,γ-difunctionalization of butenolide scaffolds.
ABSTRACT
The divergent reactivity of nitrosocarbonyls in oxidative dearomatization of ß-naphthols is reported. In the presence of quinidine catalyst, their reactions with α-unsubstituted ß-naphthols proceeded through the N-center to furnish α-imino-ß-naphthalenones in high yields. Upon exposure to α-substituted ß-naphthols in the presence of copper catalyst, an alteration of regioselectivity was observed to produce α-aminoxylation products. The reaction is scalable, tolerates a wide spectrum of functional groups, and represents a rare example of dearomatization of α-unsubstituted ß-naphthols.
ABSTRACT
A one-pot oxidative cross-dehydrogenative [2 + 3] annulation of α-amino ketones with α-keto esters at room temperature is reported. The protocol features copper/organo cooperative catalysis and provides densely functionalized pyrrolones in high yields. Subsequent reduction furnished multi-substituted pyrrolidinones which represent the core-structure of the natural product clausenamide, a lead molecule for the treatment of Alzheimer's disease.
ABSTRACT
A straightforward synthesis of 2-styrylbenzoic acids from aryl carboxylic acids is disclosed through a carboxylate-assisted coupling under Ru(II) catalysis. This protocol is simple and exhibits broad scope with high tolerance of common organic functional groups, providing good to excellent yields of diverse olefinated products. The efficacy of this protocol has been showcased through sequential syntheses of isochromanone, isocoumarin, and formal synthesis of anacardic acid derivative in good yields.
ABSTRACT
A practical and flexible strategy toward α-hydroxy-ß-amino esters and amides, which are important biological motifs, based on an organocatalytic cross-aldol reaction of in situ-generated nitrosocarbonyl intermediates followed by hydrogenation is presented. The protocol features operational simplicity, high yields, a wide substrate scope, and high regio- and diastereoselectivity profiles. The utility of this method was showcased through the synthesis of bestatin analogues and indole formation.
ABSTRACT
An unprecedented Henry reaction of in situ generated nitrosocarbonyl intermediates and concomitant denitration cascade has been developed. The reaction is catalyzed by organic base at room temperature offering α-ketoamides, a demanding scaffold for drug discovery, in high yields. An alteration of substitution pattern also produced α-keto oximes, a high-value synthon. The protocol features operational simplicity and broad substrate scope.
ABSTRACT
A practical and step-economical nitroso aldol reaction has been developed based on metal-free direct cross-coupling of ready-stock anilines with silyl enol ethers at room temperature affording α-amino ketones in high yields (up to 82%). The protocol features a one-pot cascade of nitroso compound generation, selective C-N bond formation, and N-O bond cleavage using solely inexpensive and user-friendly Oxone and displays remarkable functional group tolerance. The method was further extended to prepare densely functionalized indoles that are otherwise difficult to synthesize.