Three-Component Cascade Reactions with 2,3-Diketoesters: A Novel Metal-Free Synthesis of 5‑Vinyl-pyrrole and 4‑Hydroxy-indole Derivatives

5-Vinyl-pyrrole and 4-hydroxy-indole derivatives are synthesized by metal-free aldol/cyclization/aromatization cascade reactions of in situ generated enamines with 2,3-diketoesters. This convenient atom-economical process produces multifunctional pyrrole and indole products in moderate to good yields

Reactivity and Selectivity in Catalytic Reactions of Enoldiazoacetamides. Assessment of Metal Carbenes as Intermediates

Catalyst effectiveness for metal carbene formation and reactions has been surveyed using <i>N</i>-(<i>tert</i>-butyl)-3-[(<i>tert</i>-butyldimethylsilyl)­oxy]-2-diazo-<i>N</i>-(4-chlorobenzyl)­but-3-enamide in the formation of the products from both intramolecular C–H insertion and aromatic cycloaddition. Both products are indicators of metal carbene intermediates, and this system provides a means to assess catalysts for metal carbene formation. Donor–acceptor cyclopropene production from the reactant enoldiazoacetamide has been monitored to assess its formation, and the independently formed cyclopropene has also been used to assess metal carbene formation. Catalysts of rhodium­(II), copper­(I), silver­(I), Pd­(II), cationic Au­(I), and Zn­(II) convert the enoldiazoacetamide to the donor–acceptor cyclopropene which serves as the resting state for the intermediate metal carbene, and both the enoldiazoacetamide and its derivative cyclopropene give the same ratios of insertion to cycloaddition products. Catalysts of copper­(II) and ruthenium­(II) do not give the cyclopropene as an observable intermediate, and the product ratio from insertion/cycloaddition varies when the reactant is the enoldiazoacetate from that with its derivative cyclopropene. The variation of product ratio with the metal carbene precursor in copper­(II)-catalyzed reactions is dependent on the catalyst ligand, the solvent, and substituents of the benzyl group of the reactant. [Ru­(<i>p</i>-cymene)­Cl₂]₂ formed the products from a metal carbene intermediate with the reactant enoldiazoacetamide catalytically but with an enoldiazoacetate formed a η³-allyl ruthenium complex stoichiometrically

Reactivity and Selectivity in Catalytic Reactions of Enoldiazoacetamides. Assessment of Metal Carbenes as Intermediates

Catalyst effectiveness for metal carbene formation and reactions has been surveyed using <i>N</i>-(<i>tert</i>-butyl)-3-[(<i>tert</i>-butyldimethylsilyl)­oxy]-2-diazo-<i>N</i>-(4-chlorobenzyl)­but-3-enamide in the formation of the products from both intramolecular C–H insertion and aromatic cycloaddition. Both products are indicators of metal carbene intermediates, and this system provides a means to assess catalysts for metal carbene formation. Donor–acceptor cyclopropene production from the reactant enoldiazoacetamide has been monitored to assess its formation, and the independently formed cyclopropene has also been used to assess metal carbene formation. Catalysts of rhodium­(II), copper­(I), silver­(I), Pd­(II), cationic Au­(I), and Zn­(II) convert the enoldiazoacetamide to the donor–acceptor cyclopropene which serves as the resting state for the intermediate metal carbene, and both the enoldiazoacetamide and its derivative cyclopropene give the same ratios of insertion to cycloaddition products. Catalysts of copper­(II) and ruthenium­(II) do not give the cyclopropene as an observable intermediate, and the product ratio from insertion/cycloaddition varies when the reactant is the enoldiazoacetate from that with its derivative cyclopropene. The variation of product ratio with the metal carbene precursor in copper­(II)-catalyzed reactions is dependent on the catalyst ligand, the solvent, and substituents of the benzyl group of the reactant. [Ru­(<i>p</i>-cymene)­Cl₂]₂ formed the products from a metal carbene intermediate with the reactant enoldiazoacetamide catalytically but with an enoldiazoacetate formed a η³-allyl ruthenium complex stoichiometrically

Synthesis, Characterization, and Spectroscopic Investigation of New Iron(III) and Copper(II) Complexes of a Carboxylate Rich Ligand and Their Interaction with Carbohydrates in Aqueous Solution

New tetra-iron­(III) (K₄[<b>1</b>]·25H₂O·(CH₃)₂CO and K₃[<b>2</b>]·3H₂O·(OH)) and di-copper­(II) (Na₃[<b>3</b>]·5H₂O) complexes as carbohydrate binding models have been synthesized and fully characterized used several techniques including single crystal X-ray crystallography. Whereas K₄[<b>1</b>]·25H₂O·(CH₃)₂CO and Na₃[<b>3</b>]·5H₂O are completely water-soluble, K₃[<b>2</b>]·3H₂O·(OH) is less soluble in all common solvents including water. The binding of substrates, such as d-mannose, d-glucose, d-xylose, and xylitol with the water-soluble complexes in different reaction conditions were investigated. In aqueous alkaline media, complexes K₄[<b>1</b>]·25H₂O·(CH₃)₂CO and Na₃[<b>3</b>]·5H₂O showed coordination ability toward the applied substrates. Even in the presence of stoichiometric excess of the substrates, the complexes form only 1:1 (complex/substrate) molar ratio species in solution. Apparent binding constants, p<i>K</i>_app, values between the complexes and the substrates were determined and specific mode of substrate binding is proposed. The p<i>K</i>_app values showed that d-mannose coordinates strongest to K₄[<b>1</b>]·25H₂O·(CH₃)₂CO and Na₃[<b>3</b>]·5H₂O. Syntheses, characterizations and detailed substrate binding study using spectroscopic techniques and single crystal X-ray diffraction are reported

Stereoretentive Catalytic [3+2]-Cycloaddition/Rearrangement/Decarboxylation Reactions of Indoles with Non-Racemic Donor–Acceptor Cyclopropanes

A highly enantioselective synthesis of chiral dihydro-3H-carbazole-2-carboxylate derivatives is reported via a “one-pot” cyclopentannulation-rearrangement cascade reaction that is sequentially catalyzed by nickel(II) perchlorate hexahydrate and scandium(III) trifluoromethanesulfonate with 3-methylindole and non-racemic donor–acceptor cyclopropanes in high yields and enantioretention under mild reaction conditions. Highly diastereoselective [3+2]-cycloaddition is dependent on 3-methylindole substituents. In addition, a further transformation of these dihydro-3H-carbazole-2-carboxylates via hydrolysis and decarboxylation under unexpectedly mild reaction conditions provides straightforward access to the decarboxylated compounds in moderate yields with high retention of enantiomeric purity

Copper-Catalyzed Divergent Addition Reactions of Enoldiazoacetamides with Nitrones

Catalyst-controlled divergent addition reactions of enol­diazo­acetamides with nitrones have been developed. By using copper­(I) tetrafluoroborate/bisoxazoline complex as the catalyst, a [3+3]-cycloaddition reaction was achieved with excellent yield and enantioselectivity under exceptionally mild conditions, which represents the first highly enantioselective base-metal-catalyzed vinylcarbene transformation. When the catalyst was changed to copper­(I) triflate, Mannich addition products were formed in high yields with near exclusivity under otherwise identical conditions

Highly Regio‑, Diastereo‑, and Enantioselective Rhodium-Catalyzed Intramolecular Cyclopropanation of (<i>Z</i>)‑1,3-Dienyl Aryldiazoacetates

Chiral cyclopenta­[2,3]­cyclopropa­[1,2-<i>c</i>]­pyran-4-ones have been synthesized via dirhodium­(II)-catalyzed intramolecular cyclopropanation of (<i>Z</i>)-1,3-dienyl aryldiazoacetates. High regio-, diastereo-, and enantiocontrol were achieved using chiral dirhodium 2-phthalimide carboxylates. Preferential addition occurs at the 3,4- rather than the 1,2-double bond with the chiral dirhodium catalysts, although both outcomes occur with other transition-metal catalysts

Highly Regio‑, Diastereo‑, and Enantioselective Rhodium-Catalyzed Intramolecular Cyclopropanation of (<i>Z</i>)‑1,3-Dienyl Aryldiazoacetates

Chiral cyclopenta­[2,3]­cyclopropa­[1,2-<i>c</i>]­pyran-4-ones have been synthesized via dirhodium­(II)-catalyzed intramolecular cyclopropanation of (<i>Z</i>)-1,3-dienyl aryldiazoacetates. High regio-, diastereo-, and enantiocontrol were achieved using chiral dirhodium 2-phthalimide carboxylates. Preferential addition occurs at the 3,4- rather than the 1,2-double bond with the chiral dirhodium catalysts, although both outcomes occur with other transition-metal catalysts

Highly Regio- and Enantioselective Formal [3 + 2]-Annulation of Indoles with Electrophilic Enol Carbene Intermediates

Chiral cyclopentane-fused indolines are synthesized with high regio- and enantiocontrol by formal [3 + 2]-annulation reactions of indoles and electrophilic enol carbenes. High enantioselectivity and exclusive regiocontrol occurred with enoldiazoacetamides using a less sterically encumbered prolinate-ligated dirhodium­(II) catalyst in reactions with <i>N</i>-substituted indoles without substituents at the 2- or 3-positions via a selective vinylogous addition process. In this transformation, donor–acceptor cyclopropenes generated from enoldiazoacetamides serve as the carbene precursors to form metal carbene intermediates

Divergent Rhodium-Catalyzed Cyclization Reactions of Enoldiazo­acetamides with Nitrosoarenes

The first cyclization reactions of enoldiazo compounds with nitrosoarenes have been developed. Under the catalysis of rhodium­(II) octanoate, [3 + 2]-cyclization between enoldiazoacetamides and nitrosoarenes occurred through cleavages of the enol double bond and the amide bond, thus furnishing fully substituted 5-isoxazolone derivatives. Upon changing the catalyst to rhodium­(II) caprolactamate, the reaction pathway switched to an unprecedented formal [5 + 1]-cyclization that provided multifunctionalized 1,3-oxazin-4-ones with near exclusivity under otherwise identical conditions. Mechanistic studies uncovered distinct catalytic activities and reaction intermediates, which plausibly rationalized the novel reactivity and catalyst-controlled chemodivergence. Furthermore, a mechanism-inspired enantioselective rhodium-catalyzed reaction of γ-substituted enoldiazoacetamide with nitrosobenzene produced highly enantioenriched heterocycle-linked trialkylamine