Synthesis of Azonia Aromatic Heterocycles Bearing 6-6-6-5-6 Pentacyclic Core via Intramolecular [4 + 2]-Cycloaddition and Oxidative Aromatization Reaction Sequence in One Pot.

Cationic aza-heterocycle-fused compounds have gained wide applications in materials science, biological applications, and synthetic organic chemistry. In this report, synthesis of benzothiazolochromenopyridinium tetrafluoroborates, a novel molecular scaffold, bearing 6-6-6-5-6 pentacyclic core is described that proceeds via (i) piperidine-catalyzed Knoevenagel condensation between 2-propargyloxyarylaldehydes bearing internal alkynes and 2-benzothiazoleacetonitrile, (ii) intramolecular formal [4 + 2]-cycloaddition, and (iii) crucial molecular oxygen-mediated oxidative aromatization reaction sequence in one pot. These quaternary pyridinium salts are obtained at ambient temperature in good to high yields.

K2CO3-Catalyzed Rapid Conversion of N-Sulfonylhydrazones to Sulfinates.

N-Sulfonylhydrazones derived from alkyl, aryl, and heteroaryl aldehydes and ketones undergo rapid conversion into the corresponding sulfinates when heated with 10 mol % K2CO3 in N,N'-dimethylethylene urea (DMEU) at elevated temperature. The reaction conditions are amenable to several functional groups and suitable for gram-scale synthesis. Under these base-catalyzed conditions, N-tosylhydrazones derived from O-allylated and O-propargylated 2-hydroxyarylaldehydes do not undergo the well-established intramolecular [3 + 2]-cycloaddition reactions and generate corresponding sulfinates in good yields. The base-catalyzed transformation proceeds via crucial rapid intermolecular protonation of the diazo intermediate 11 to generate diazonium ion 12, which upon nucleophilic displacement by the sulfonyl ion 10 provides the desired sulfinate selectively.

Wittig Ylide Mediated Decomposition of N-Sulfonylhydrazones to Sulfinates.

N-Sulfonylhydrazones generate sulfinates selectively when treated with a stabilized Wittig ylide in a polar aprotic solvent at elevated temperature. The transition metal and base free decomposition method is applicable to N-sulfonylhydrazones generated from a number of aromatic and heteroaromatic aldehydes and ketones. In the case of N-tosylhydrazones derived from O-allyl and O-propargyl salicylaldehydes, selective formation of sulfinate occurs over intramolecular [3 + 2]-cycloaddition reaction.

An organocatalytic asymmetric Nazarov cyclization.

An organocatalytic asymmetric Nazarov cyclization of diketoesters that proceeds by means of a dual activation mechanism has been developed. Screening of a number of catalysts led to a new thiourea that incorporates a primary amino group. The method gives rise to cyclic products with two adjacent quaternary asymmetric carbon atoms, one of which is an all-carbon stereocenter, with complete or nearly complete diastereoselectivity and in high or very high enantiomeric excess. A brief and very convenient synthesis of the acyclic diketoester starting materials through nucleophilic addition to a ketene is also described.

Organocatalytic asymmetric aza-Nazarov cyclization of an azirine.

An unusual organocatalytic asymmetric cyclization of a ketoazirine that is accompanied by a kinetic resolution leads to 4-hydroxy-3-oxo-1,2,3,6-tetrahydropyridine-2-carboxylates in >99/1 er.

Enamine-iminium ion Nazarov cyclization of alpha-ketoenones.

The mono-triflate salts of some chiral nonracemic 1,2-diamines react with alpha-ketoenones in a stoichiometric reaction to form products of the Nazarov cyclization in high enantiomeric ratios. The mechanism appears to involve rearrangement of an enamine-iminium ion.

Interrupting the Nazarov cyclization with indoles.

A carbon-terminated interrupted Nazarov reaction is described. The trimethylsilyl enol ethers derived from propargyl vinyl ketones undergo selective proton transfer at the distal acetylenic carbon atom to provide allenyl vinyl ketones as transient intermediates. In the presence of indoles, a cascade of reactions is initiated that converts the initially formed pentadienyl cations to cyclopentenones bearing a quaternary alpha carbon atom.