1,3-Dipolar Cycloaddition of 3-Chromonyl-Substituted Glycine Imino Esters with Arylidenes and in†situ Diastereodivergent via Retrocycloaddition.

1,3-Dipolar cycloaddition through in situ generation of azomethine ylide provides a straightforward and critically important sustainable approach for access to diverse pyrrolidine chemical space. Herein, we developed a metal-free AcOH-activated 1,3-dipolar cycloaddition protocol that permits the synthesis of uncommon pyrrolidine cycloadducts with excellent diastereoselectivity. The challenging substrates of 3-formylchromone, glycine ester.HCl and arylidene dipolarophile were reacted in the presence of AcONa, which played a dual role as a base and AcOH source, to deliver firstly endo-cycloadduct. Under prolonged reaction time at room temperature or heating; the endo-adduct underwent diastereodivergent via a sequence of retro-cycloaddition, stereomutation of the generated syn-dipole into anti-dipole and recycloaddition; to furnish the scarcely known exo'-cycloadduct with high diastereodivergency. The reaction worked well with a broad range of substrates and the stereochemistry of the obtained cycloadducts was determined without ambiguity using NMR- and X-ray analysis. Experimental and theoretical DFT calculation studies were performed to support the proposed reaction mechanism and elucidate the key role of AcOH in the process which seems more beneficial than other transition metal-catalyzed processes.

Crystal structure and Hirshfeld surface analysis of N-[(Z)-(2-hy-droxy-phen-yl)methyl-idene]aniline N-oxide.

The conformation of the title compound, C13H11NO2, is partially determined by a strong, intra-molecular O-H⋯O hydrogen bond. The crystal packing consists of strongly corrugated layers parallel to the ac plane and associated through C-H⋯π(ring) inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most significant contributions to the crystal packing are from H⋯H (44.1%), C⋯H/H⋯C (29.4%) and O⋯H/H⋯O (17.3%) contacts.

Nitro-Substituted Benzaldehydes in the Generation of Azomethine Ylides and Retro-1,3-Dipolar Cycloadditions.

1,3-Dipolar cycloaddition of 2- and 3-nitrobenzaldehydes with 2-aminomethylpyridine and ethyl (2E)-2-cyano-3-(4-nitrophenyl)prop-2-enoate yielded endo-cycloadducts as the sole products under various reaction conditions. Fortuitously, 4-nitrobenzaldehyde behaved differently in three- and four-component cascades to produce a mixture of endo- and exo'-cycloadducts. This reaction is solvent- and temperature-dependent, and consequently, both the endo- and exo'-cycloadducts were synthesized in an excellent regio-, stereo-, and chemoselective fashion. Retro-1,3-dipolar cycloadditions of the endo-cycloadducts were conducted under mild reaction conditions, and the generated syn-dipoles were stereomutated into anti-dipoles which recycloadded with the dipolarophiles to provide the exo'-cycloadducts. Mechanistic studies were carried out to support the proposed mechanisms. Unprecedentedly, particular arylidene scaffolds participated as aldehyde or activated methylene precursors. Density functional theory calculations were performed to shed light on the importance of AcOH in the generation and isomerization of dipoles and to explain the high selectivity and the possibility of retro-cycloaddition.

A facile palladium catalysed 3-component cascade route to functionalised isoquinolinones and isoquinolines.

Palladium catalysed three component cascade process, involving coupling of 2-iodobenzoates, -benzaldehydes, or acetophenones with substituted allenes and ammonium tartrate as an ammonium surrogate, provides a novel and facile route to substituted functionalised isoquinolinones and isoquinolines in good yields.

Stereoselective Pd(0) catalysed five component cascade synthesis of complex Z,Z-bisallylamines.

Catalytic 5-component cascade chemistry provides an effective stereo- and regioselective route to novel multi-functional Z,Z-bisallylamines. The process, which is capable of considerable further extension, utilises ammonium tartrate as a novel ammonia source which avoids the use of ammonia gas or aqueous ammonia.

Exploiting adamantane as a versatile organic tecton: multicomponent catalytic cascade reactions.

3- And 9-component Pd(0) catalysed assembly of allenes, aryl iodides and N-nucleophiles with concomitant installation of trisubstituted Z-alkenes is readily achieved.

Useful dual Diels-Alder behavior of 2-azetidinone-tethered aryl imines as azadienophiles or azadienes: a beta-lactam-based stereocontrolled access to optically pure highly functionalized indolizidine systems.

Imines derived from 4-oxoazetidine-2-carbaldehydes have been found to be versatile Diels-Alder reagents in that they exhibit two reactivity patterns. 2-Azetidinone-tethered imines undergo diastereoselective reaction with Danishefsky's diene in the presence of different Lewis acids. The effect of the amount of catalyst on the conversion rate as well as on the product ratio has been studied. Under standard reaction conditions, indium(III) chloride and zinc(II) iodide provided the best yields, and indium(III) triflate the highest diastereoselectivity in the Lewis acid promoted aza-Diels-Alder cycloaddition. Treatment of the aforementioned imines with cyclopentadiene, 2,3-dimethyl-1,3-butadiene or 3,4-dihydro-2 H-pyran led to cycloadducts arising from inverse electron-demand condensation involving the beta-lactam-tethered aryl imine as the heterodiene component. In addition, the first methodology for preparing indolizidines from beta-lactams has been developed. This process involves amide bond cleavage of the beta-lactam ring in the aza-Diels-Alder cycloadducts with concomitant cyclization. Full chirality transfer occurs when the reaction is performed with an enantiomerically pure substrate.

Efficient entry to highly functionalized beta-lactams by regio- and stereoselective 1,3-dipolar cycloaddition reaction of 2-azetidinone-tethered nitrones. Synthetic applications.

Racemic as well as optically pure 2-azetidinone-tethered nitrones, both cyclic and acyclic, were smoothly prepared from 4-oxoazetidine-2-carbaldehydes. The regio- and diastereoselectivities of the intermolecular 1,3-dipolar cycloaddition reactions of 2-azetidinone-tethered nitrones with substituted alkenes and alkynes were investigated. 2-Azetidinone-tethered nitrones on reacting with various dipolarophiles yielded isoxazolinyl-, isoxazolidinyl-, or fused polycyclic-beta-lactams, exhibiting good regio- and facial stereoselectivity in the most of the cases. In addition, some interesting transformations of these cycloadducts were performed, yielding aziridinyl beta-lactams or functionalized beta-alkoxycarbonyl gamma-lactams (derivatives of the aza analogue of paraconic acid).

Stereoselective Synthesis of 3-Substituted 4-(Formyloxy)-2-azetidinones by the Unusual Baeyer-Villiger Reaction of beta-Lactam Aldehydes. Scope and Synthetic Applications.

The Baeyer-Villiger oxidation of 4-formyl-beta-lactams 1with m-CPBA gave 4-(formyloxy) beta-lactams 2 in a simple, efficient, and totally stereoselective process. This reaction is one of the scarce examples of the preferred migration of a carbon moiety in an aliphatic aldehyde. The influence of the substituents at N1 and C3 of the four-membered ring in the Baeyer-Villiger rearrangement has been studied. Thus, alkyl, alkenyl, aryl, and alkyloxy 3-substituted-1-(p-anisyl)-2-azetidinones 1 form exclusively 4-(formyloxy) beta-lactams 2. Amide or acetoxy substituents at C3 of the four-membered ring produce mixtures of 4-(formyloxy) beta-lactams 2and 4-carboxy beta-lactams 5. The exclusive formation of carboxy derivatives is observed sometimes for 1-alkyl-substituted-2-azetidinones 1. 4-(Formyloxy) beta-lactams 2 are suitable starting materials to prepare different 4-unsubstituted beta-lactams 9 using beta-hydroxy amides 8 as isolable intermediates. The overall transformation 4-formyl-2-azetidinone to 4-unsubstituted beta-lactam is an easy and convenient stereoselective route to these interesting types of compounds.