Synthesis of 3,5-disubstituted isoxazoles by domino reductive Nef reaction/cyclization of ß-nitroenones.

ß-Nitroenones can be efficiently converted into 3,5-disubstituted isoxazoles by using tin(II)chloride dihydrate and ethyl acetate as a reducing agent and solvent, respectively. Products are obtained in good yields and several functional groups are tolerated thanks to the mild reaction conditions.

Overcoming the Usual Reactivity of ß-Nitroenones: Synthesis of Polyfunctionalized Homoallylic Alcohols and Conjugated Nitrotriene Systems.

Herein, we report a new application of ß-nitroenones as valuable building blocks for the preparation of polyfunctionalized homoallylic alcohols; they can be used as key precursors of conjugated nitrotriene systems. The synthesis of homoallylic alcohols was performed exploiting the chemoselective addition of metal allylating agents to the ketone moiety vs the nitroalkenyl group. The conversion of alcohols into nitrotrienes was achieved under Lewis-acid-promoted conditions. Both classes of compounds were obtained in good to excellent yields.

Synthesis and practical applications of 2-(2-nitroalkyl)pyrroles.

Functionalization of pyrroles introducing a 2-nitroalkyl moiety allows the formation of nitro-containing compounds to be used as pivotal intermediates for the synthesis of bioactive compounds. The reaction of pyrroles with nitroalkenes under the Friedel-Crafts conditions allows a direct entry to 2-(2-nitroalkyl)pyrroles. This approach can also be used for the preparation of enantioenriched derivatives exploiting asymmetric catalysis. In a complementary fashion, the Henry reaction between 2-formylpyrroles and nitroalkanes generates the corresponding nitroaldol products which upon dehydration and reduction of the intermediate 2-pyrrolylnitroethene efficiently afford 2-(2-nitroalkyl)pyrroles. This review article summarizes the most relevant procedures for the preparation of 2-(2-nitroalkyl)pyrroles during the last two decades as well as their significant practical applications.

Tryptophol and derivatives: natural occurrence and applications to the synthesis of bioactive compounds.

Covering: up to 2018 Tryptophol (indole-3-ethanol) is a metabolite produced by plants, bacteria, fungi and sponges. This review reports on the natural occurrence, bioactivity and various synthetic approaches to the preparation of tryptophol and its derivatives. Syntheses of various naturally occurring tryptophol derivatives known for their enhanced pharmacological profile are also presented.

Synthetic Approach to the Preparation of (2-Acetoxy)allyl Nitro Compounds.

A synthetic approach to a new class of allyl nitro derivatives is reported. (2-Acetoxy)allyl nitro compounds have been prepared for the first time in a four-step procedure by a preliminary reaction of nitroalkanes with 2-(phenylselenyl)acetaldehyde. After the acetylation of the obtained nitro alcohols, the unsaturation is installed by an oxidation reaction involving the phenylselenyl group followed by a thermal elimination. The oxidation process is accomplished under flow conditions ensuring a notable lowering of overoxidation by products observed in batch.

Regioselective Direct C-Alkenylation of Indoles.

The direct introduction of alkenyl groups into the indole framework avoiding its preliminary functionalization can be carried out using different synthetic strategies. Transition-metal complexes facilitate the C-H activation of indoles or alkenes allowing an efficient Csp2 - Csp2 bond formation. The hydroindolation of alkynes catalyzed by the same metal complexes or various acidic promoters can also be pursued for the alkenylation process. Conjugate addition of electron-poor alkenes and direct condensation of carbonyl derivatives with indoles are also of interest for this purpose. The regiochemical control can be exploited using the intrinsic C-3 reactivity of the indole ring. The introduction of a suitable directing group at the nitrogen atom allows the preparation of C-2 alkenylated derivatives by transition metal catalyzed reactions. This review collects the fundamental contributions in this field reported in literature during the last fifteen years.

Sulfonyl Azoles in the Synthesis of 3-Functionalized Azole Derivatives.

Sulfonyl indoles, as well as related azolyl derivatives, have been recently introduced in synthesis as stable precursors of reactive indolenine intermediates. This personal account reports on the discovery of sulfonyl azoles and their practical utilization in many synthetic processes for the preparation of functionalized 3-substituted indoles, indazoles, and pyrroles. The indolenine intermediates obtained by treatment of sulfonyl azoles with Brønsted bases or Lewis acids can be considered as vinylogous imino derivatives that can be made to react with different nucleophilic reagents. These include organometallic reagents, reducing agents, stabilized carbanions, and heteronucleophiles. The controlled and mild conditions for the generation of indolenines from sulfonyl azoles make these substrates particularly useful in asymmetric synthesis, exploiting organo- or metal-catalyzed processes. Although less exploited, sulfonyl indoles can also be involved in photochemical processes for the preparation of polycyclic derivatives.

Ketosulfonyl indoles in the regiodefined synthesis of tryptophols and related indole derivatives.

Reduction of ketosulfonyl indoles with sodium borohydride provides a ready entry to tryptophols in a regiocomplementary fashion with respect to the traditional oxirane ring-opening by indoles under Friedel-Crafts conditions. Compared to traditional ß-ketosulfones, ketosulfonyl indoles show a peculiar behavior since they undergo a Lewis acid promoted elimination of the arylsulfonyl group allowing the preparation of indolyl-substituted 1,4-dicarbonyl derivatives.

Synthesis of 3-substituted indoles via reactive alkylideneindolenine intermediates.

Elimination of suitable leaving groups from 3-substituted indoles under basic or acidic conditions readily provides alkylideneindolenine intermediates that may react with a large variety of nucleophilic reagents. This article highlights some recent developments of this synthetic approach for the preparation of functionalized indole derivatives.

Reaction of carbon nucleophiles with alkylideneindazolium and alkylideneindolium ions generated from their 3-(1-arylsulfonylalkyl) indazole and indole precursors.

Lewis acid promoted elimination of p-toluenesulfinc acid from sulfonyl indazoles and sulfonyl indoles generates the corresponding iminium ion that reacts with allyltin reagents, silyl enol ethers, silyl ketene acetals and electron-rich aromatics leading to functionalized indazole and indole derivatives.

Nitroalkanes as central reagents in the synthesis of spiroketals.

Nitroalkanes can be profitably employed as carbanionic precursors for the assembly of dihydroxy ketone frameworks, suitable for the preparation of spiroketals. The carbon-carbon bond formation is carried out exploiting nitroaldol and Michael reactions, while the nitro to carbonyl conversion (Nef reaction) ensures the correct introduction of the keto group. Several spiroketal systems endowed with considerable biological activity can be prepared using this synthetic strategy.

Simplified synthesis of 3-(1-arylsulfonylalkyl) indoles and their reaction with Reformatsky reagents.

A simple procedure for the preparation of 3-(1-arylsulfonyl-alkyl) indoles by three-component condensation of indoles, carbonyls, and arenesulfinic acids is presented. The obtained products undergo a Reformatsky reaction leading to alkyl 3-(3-indolyl) alkanoates and (3-indolyl) ketones.

An efficient diastereoselective route to differentially protected anti-4-amino-1-alken-3-ols.

Zinc-promoted hydroxyallylation of alpha-amidoalkyl arylsulfones 4 using 3-bromo-propenyl methyl carbonate 5 proceeds smoothly in DMF at room temperature to afford high yields of differentially protected anti-1,2-amino alcohols 6.

Solventless clay-promoted Friedel-Crafts reaction of indoles with alpha-amido sulfones: unexpected synthesis of 3-(1-arylsulfonylalkyl) indoles.

Friedel-Crafts reaction of indoles with alpha-amido sulfones in the presence of montmorillonite K-10 leads unexpectedly to 3-(1-arylsulfonylalkyl) indoles in good yield. The obtained products can be further desulfonylated under reductive or alkylative conditions giving linear and branched 3-substituted indoles.

Reactivity of chiral alpha-amidoalkylphenyl sulfones with stabilized carbanions. stereoselective synthesis of optically active 1-aminopyrrolizidine.

Metal enolates and functionalized allylzinc reagents react with optically active alpha-amidoalkylphenyl sulfones to give N-carbamoylamino derivatives with variable levels of anti diastereoselectivity. Zinc enolates provide comparable results with respect to lithium enolates in terms of diastereoselectivity but afford beta-amino ester derivatives in lower yield. The synthetic utility of the obtained chiral N-carbamoylamino esters is demonstrated by the first enantioselective synthesis of (-)-1-aminopyrrolizidine a central intermediate for the preparation of various biologically active substances.