Synthesis of novel isoxazolines and isoxazoles of N-substituted pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives through [3+2] cycloaddition

3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 3 was prepared by an intramolecular cyclization of N-(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl) acetamide 2 in ethanol in the presence of piperidine. N-allylation and N-propargyl alkylation of N-substituted pyrazolo[3,4-d] pyrimidin-4(5H)-one 3 yielded the corresponding dipolarophiles 4 and 5 which afford by condensation with arylnitrile oxides in toluene the expected new isoxazolines 6 and isoxazoles 7, respectively. On the other hand, the aminopyrazole 1 in refluxing with ethanol in the presence of sodium hydroxide afforded the corresponding carboxamide 8, which then, was converted to its ethyl 3-methyl-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d] pyrimidine-6-carboxylate 9 with neat diethyl oxalate. The dipolarophile 10 on regiospecific 1,3-dipolar cycloaddition with arylnitrile oxides affords isoxazoles 11 and the unexpected deethoxycarbonylated isoxazoles 12. The target compounds were completely characterized by ¹H NMR, ¹³C NMR, IR and HRMS.     

A [4 + 2] cycloaddition strategy to pyridine boronic ester derivatives

Alkynylboronate cycloadditions of 1,4-oxazin-2-ones and 2-pyrazinones provide a direct and regioselective route to functionalized pyridine boronic ester derivatives.     

Stability of boronic esters - Structural effects on the relative rates of transesterification of 2-(phenyl)-1,3,2-dioxaborolane

Relative rates of reaction of the achiral cyclic phenylboronic ester 2-(phenyl)-1,3,2-dioxaborolane with a wide variety of structurally modified diols, have been studied to understand the factors influencing the relative stabilities of boronic esters. It is found that the alkyl substituents on the α-carbons of diols slow down the transesterification, but produce thermodynamically more stable boronic ester. Six-membered boronic esters are thermodynamically more stable than their corresponding five-membered analogs. Amongst cyclic 1,2-diols, cis-1,2-cyclopentanediol displaces ethylene glycol instantaneously whereas trans-1,2-cyclopentanediol is totally unreactive, which suggests that the cis-stereochemistry of the 1,2-diol is a prerequisite for transesterification. Among the 1,5-diols, diethanolamine displaces ethylene glycol quite rapidly forming a more stable bicyclic chelate in which nitrogen is attached to boron by a coordinating bond (as evident by ¹¹B NMR spectroscopy). The oxygen atom of di(ethylene glycol) and the sulfur atom of 2,2′-thiodiethanol do not assist in displacing the ethylene glycol from their boronic esters.     

Aqueous-phase deactivation and intramolecular [2 + 2 + 2] cycloaddition of oxanorbornadiene esters

Both inter- and intramolecular degradation pathways were identified for the aqueous phase deactivation of oxanorbornadiene (OND) electrophiles, and propargylic OND esters were found to undergo facile intramolecular [2 + 2 + 2] homo-Diels-Alder cycloaddition in polar media.     

Photochemical [3 + 2] cycloaddition of 2-cyanochromone to olefins

Irradiation of 2-cyanochromone in the presence of olefins gave rise to [3 + 2] cycloadducts together with the formation of normal [2 + 2] cycloadducts with the product ratio being temperature-dependent. The mechanism involving a vinyl nitrene intermediate was proposed.     

GaCl3-assisted [2 + 3] cycloaddition: a route to tetrazaphospholes

The GaCl3-assisted [2 + 3] cycloaddition of Mes*-N=P-Cl (Mes* = 2,4,6-tBu3C6H2) with trimethylsilylazide (TMS-N3) results in the formation of the first tetrazaphosphole, stabilized as a GaCl3 adduct in high yields (>96%).     

Use of temporary tethers in the intramolecular [2+2] photocycloaddition reactions of tetrahydrophthalimide derivatives: a new approach to complex tricyclic lactones

The intramolecular [2+2] photocycloaddition reactions of a series of alkenols tethered to ethanolamine, l-(+)-valinol and R-(−)-2-phenylglycinol derived 3,4,5,6-tetrahydrophthalimides via a carbonate or silicon linkage have been examined. These [2+2] photocycloadditions gave the corresponding cyclobutanes in high yield with complete endo control in all cases and with diastereoselectivities as high as 8:1 with the chiral tethers. The cleavage of the temporary tethers by either desilylation or hydrolysis provided the endo diols. Cleavage of the ethanolamine linkage by reduction/hydrolysis precipitated an acid-catalysed fragmentation/ring expansion sequence to generate complex tricyclic lactones.     

Formal [6+3] cycloaddition of fulvenes with 2H-azirine: a facile approach to the [2]pyrindines system

2H-Azirine reacts with fulvenes to give either alkylated fulvene azirines (ultrasound) or the formal [6+3] cycloaddition adducts (Lewis acid). The later constitutes an efficient and novel route to [2]pyrindines.     

Organotransition metal [3+2] cycloaddition reactions

The review, covering the literature of roughly the last three decades, describes the [3+2] cycloaddition reactions of metalla dipolarophiles M=X with organic 1,3-dipoles, and of metalla 1,3-dipoles, M---X=Y and X---M=Y, with organic dipolarophiles. The resulting 5-membered metalla heterocycles can undergo consecutive insertion and/or reductive elimination reactions to give synthetically interesting organic heterocycles. The reactivity of the organometal 1,3-dipoles is explained by extensive series of isolobal transformations to classic organic 1,3-dipoles.     

Synthesis and reactivity of new functionalized Pd(II) cyclometallated complexes with boronic esters

Treatment of the functionalized Schiff base ligands with boronic esters 1a, 1b, 1c and 1d with palladium (II) acetate in toluene gave the polynuclear cyclometallated complexes 2a, 2b, 2c and 2d, respectively, as air-stable solids, with the ligand as a terdentate [C,N,O] moiety after deprotonation of the -OH group. Reaction of 1j with palladium (II) acetate in toluene gave the dinuclear cyclometallated complex 5j. Reaction of the cyclometallated complexes with triphenylphosphine gave the mononuclear species 3a, 3b, 3c, 3d and 6j with cleavage of the polynuclear structure. Treatment of 2c with the diphosphine Ph₂PC₅H₄FeC₅H₄PPh₂ (dppf) in 1:2 molar ratio gave the dinuclear cyclometallated complex 4c as an air-stable solid.Deprotection of the boronic ester can be easily achieved; thus, by stirring the cyclometallated complex 3a in a mixture of acetone/water, 3e is obtained in good yield. Reaction of the tetrameric complex 2a with cis-1,2-cyclopentanediol in chloroform gave complex 2c after a transesterification reaction. Under similar conditions complexes 3a and 3d behaved similarly: with cis-1,2-cyclopentanediol, pinacol or diethanolamine complexes 3c, 3b, 3g and 3f, were obtained. The pinacol derivatives 3b and 3g experiment the Petasis reaction with glyoxylic acid and morpholine in dichloromethane to give complexes 3h, and 3i, respectively.     

Rh-catalyzed enantioselective [2 + 2] cycloaddition of alkynyl esters and norbornene derivatives

[reaction: see text] The enantioselective [2 + 2] cycloaddition of alkynes possessing an ester functionality and norbornene derivatives proceeded efficiently using a chiral rhodium catalyst. The chiral tri- and tetracyclic cyclobutenes were obtained in moderate to high ee.     

Tandem [2+2] cycloaddition and Cope rearrangement in reactions of cross-conjugated azatrienes with conjugated ketenes: a facile single step synthesis of novel azocinone derivatives

A facile single step synthesis of novel azocinone derivatives involving tandem [2+2] cycloaddition and Cope rearrangement in the reactions of cross-conjugated azatrienes with vinyl/isopropenyl ketenes supported by theoretical calculations is reported.     

Regioselective preferential CH activation of sterically hindered 1,3-dienes over [4+2] cycloaddition

The study of Pd-catalyzed preferential CH activation of sterically hindered α, β-olefinic indoles onto alkenes beyond [4 + 2] cycloaddition has been described. The carbazole derivatives were readily synthesized via activation of vinylic CH bonds with excellent regioselectivity. Further, the one-pot strategy has been employed for the synthesis of tricyclic carbazoles. The double and triple CH activation followed by concomitant Michael addition provides an economical approach for the synthesis of N-protected carbazole. A wide range of alkenes at the α- and β-position are compatible with this reaction. The mechanistic and X-ray crystallographic studies supported the designed chemistry of CH activation.     

Ni-catalyzed [3+2+2] cycloaddition of ethyl cyclopropylideneacetate and 1,3-diynes. Application to the three-component cycloaddition

The Ni-catalyzed [3+2+2] cocyclization between ethyl cyclopropylideneacetate (1) and 1,3-diynes afforded cycloheptadiene derivatives. The three-component reaction of 1, 1,3-diynes, and alkynes proceeded with good yield and high selectivity. Scope of the substrates was studied, and the origin of chemo- and regioselectivity of the reaction is discussed.     

Palladium-catalyzed [3+2] intramolecular cycloaddition of alk-5-ynylidenecyclopropanes: a rapid,practical approach to bicyclo[3.3.0]octenes

Readily accessible hex-5-ynylidenecyclopropane derivatives cycloisomerize to bicyclic five-membered carbocycles upon heating with catalytic amounts of a palladium complex.