Synthesis of new p-quinone methide containing morpholine fragment: access to (diarylmethyl)phosphonamidates with antitumor activity

Novel (diarylmethyl)phosphonamidates containing 2,6-di-tert-butylphenol and heterocycle moieties were synthesized by 1,6-conjugate addition of phosphorylated p-quinone methide with morpholine fragment to 2,6-diaminopyridine or 1,3-diaminobenzene. In the case of an acid-catalyzed reaction of p-quinone methide with sesamol, morpholine was cleaved to form 1,2-benzoxaphosphole substituent. Cytotoxic effects of starting compounds and obtained products were evaluated towards human cancer and normal cells.     

Halogenation of N-substituted p-quinone imines and p-quinone oxime esters: III. Regioselectivity in the halogenation of N-aroyl(arylsulfonyl)oxyimino-2,5-cyclohexadienones

Halogenation of 4-aroyl(arylsulfonyl)oxyimino-2,5-cyclohexadienones is not accompanied by change of the configuration at the nitrogen atom. p-Benzoquinone oxime ethers and esters take up halogens in a regioselective fashion at the syn-C-C bond of the quinoid ring. The main factor responsible for regioselective addition of halogens is configuration at the nitrogen atom, which determines the stability of intermediate halogenonium ion.     

Halogenation of N-substituted p-quinone imines and p-quinone oxime esters: IV. Chlorination and bromination of N-arylsulfonyl-2(3)-methyl(2-chloro)-1,4-benzoquinone monoimines

The addition of halogens to N-arylsulfonyl-1,4-benzoquinone imines, which exist in a solution as Z and E isomers, is controlled by the steric factor. Z-E Isomerization strongly affects the stability of cyclohexene structures formed by halogenation of 1,4-benzoquinone imines. The halogenation of N-arylsulfonyl-1,4-benzoquinone imines was found to be accompanied by prototropic rearrangement.     

Visible-light mediated trifluoromethylation of p-quinone methides by 1,6-conjugate addition using pyrylium salt as organic photocatalyst

A transition metal free visible light mediated organo photoredox catalyzed trifluoromethylation of p-quinone methides (p-QMs) to construct fluoro-analogs of dichlorodiphenyltrichloroethane (DDT) is reported using a bench stable, inexpensive Langlois reagent as a trifluoromethyl radical source. This protocol could generate a benzylic C(sp³)-CF₃ bond with excellent yield under mild reaction conditions using 1,6-conjugate addition/aromatization of trifluoromethyl radical in the absence of any external additives. Further, we demonstrate di-trifluoromethylation and gram scale synthesis of this reaction.     

Deacylative 1,6-addition of Bestmann-Ohira reagent to p-quinone methides for the synthesis of α-diazo-β-diarylphosphonates and cis-stilbenyl phosphonates

The role of Bestmann-Ohira Reagent (BOR) as a conjugate addition partner is reported for the first time. Deacylation of BOR in the presence of ethanolic KOH and 1,6-addition of the resulting diazophosphonate anion to p-quinone methides (PQMs) provides β-disubstituted α-diazophosphonates in good to excellent yields in most cases. Such 1,6-adducts further undergo Rh-catalyzed elimination of the diazo group and 1,2-migration of the phenolic group to afford cis-stilbenylphosphonates with high E-selectivity. The migration of the phenolic group presumably takes place via a spirocyclopropane intermediate derived from the Rh-carbenoid.     

Probing the spatial requirements for [60]fullerene-[60]fullerene π-stacking and the syn addition of [60]fullerenes across acenes

The reaction between 2 equiv of [60]fullerene and 6,8,15,17-tetraphenylheptacene-7,16-quinone leads to both cis and trans-bis[60]fullerene adducts. This result contrasts sharply with the highly diastereoselective syn additions of [60]fullerenes across 6,13-diphenylpentacene and 6,8,15,17-tetraphenylheptacene. The importance of spatially dependent [60]fullerene-[60]fullerene π-stacking interactions in promoting a syn addition of [60]fullerenes is discussed.     

Concise and diastereoselective approach to syn- and anti-N-tosyl-α-hydroxy β-amino acid derivatives

The methyl diazoacetate and aryl (N-tosyl)imines can be transformed into syn or anti α-hydroxy β-amino esters with high diastereoselectivities in three steps: the base promoted nucleophilic condensation of the methyl diazoacetate and aryl (N-tosyl)imines to give β-(N-tosyl)amino α-diazoesters, followed by oxidation with Oxone^® to generate α-oxo esters, which were reduced with NaBH₄ to yield the anti-N-tosyl-α-hydroxy β-amino ester, or hydrogenated with Pd/C (10%) as the catalyst to yield corresponding syn isomer, both in high diastereoselectivity.     

Regio-and stereoselectivity in the halogenation of methyl tricyclo[4.1.0.02,7]heptane-1-carboxylate

Conjugate halogenation of methyl tricyclo[4.1.0.0^2,7]heptane-1-carboxylate by the action of N-iodoand N-bromosuccinimides in the presence of halide ions occurs exclusively at the central bicyclobutane C¹–C⁷ bond via electrophilic attack on the C¹ atom, leading to endo,syn-adducts of the norpinane series. Reactions of the title compound with iodine, dibromotetrachloroethane, and (dichloro-λ³-iodanyl)benzene give not only the corresponding 6,7-endo,syn-dihalonorpinane but also its epimer at C⁶, indicating radical mechanism of the halogenation. The regio-and stereoselectivity observed in these ionic and radical reactions are discussed in terms of the results of nonempirical MP2/STO-3G calculations of appropriate cationic and radical intermediates.     

About the stereoselectivity control in reactions of chiral ortho-sulfinyl benzyl carbanions with aldehydes

Reactions of aliphatic and aromatic aldehydes with the benzyllithium derived from 2-p-tolylsulfinyl ethylbenzene yield mixtures of mainly two compounds, anti-3 and syn-4, epimers at hydroxylic carbon, easily separated by chromatography and desulfinylated into enantiomerically pure 1-alkyl (or aryl)-2-phenyl-1-propanols. The observed stereoselectivity at C(1) and C(2) is analyzed to the light of the steric and electronic effects of the substituents.     

Ruthenium- and lipase-catalyzed DYKAT of 1,2-diols: an enantioselective synthesis of syn-1,2-diacetates

Regio- and stereoselective lipase-catalyzed kinetic resolutions were investigated for some unsymmetrical, secondary/secondary syn-diols. Candida antarctica lipase B-catalyzed transesterifications of a few aryl/alkyl- and alkyl/alkyl 1,2-diols were coupled in one-pot for efficient ruthenium-catalyzed epimerization and intramolecular acyl migration to give a dynamic kinetic asymmetric transformation (DYKAT) affording enantioenriched (ee up to >99%) syn-diacetates as the main diastereomers (syn:anti ∼2:1 to 10:1).     

Electronic structure of π-systems. Studies of electronic structures and tautomeric transformations of a series of 4-methyl-8-(R-phenylazo)dihydrofuro[2,3-<Emphasis Type="Italic">h</Emphasis>]coumarin-9-ones

Tautomeric transformations of a series of 4-methyl-8-(R-phenylazo)dihydrofuro[2,3-h]-coumarin-9-ones were studied by ¹H NMR, IR, electronic absorption spectroscopy, mass spectrometry, and quantum chemistry methods. The obtained results suggest that (p-R-phenyl)-derivatives exist in the quinone hydrazone form, while (o-R-phenyl)derivatives exist as a mixture of quinone hydrazone and azo enol tautomers with domination of the former. The anti-quinone hydrazone tautomers with a strong intramolecular hydrogen bond are more favorable than the syn-quinone hydrazone tautomers.     

Halogenation of N-substituted p-quinone monoimines and p-quinone monooxime ethers: XIV. Halogenation of N-[arylsulfonylimino(phenyl)methyl]-2,5-dialkyl-1,4-benzoquinone monoimines and their reduction products

Despite steric hindrances created by the bulky substituent on the nitrogen atom, halogenation of 2,5-dialkyl-N-[arylsulfonylimino(phenyl)methyl]-1,4-benzoquinone monoimines fairly readily gives their derivatives having two halogen atoms in the quinoid ring.     

Halogenation of N-substituted para-quinone monoimines and para-quinone monoximes ethers: IX. Halogenation of N-aroyl-2,6(3,5)-dimethyl-1,4-benzoquinone monoimines and their reduced forms

At the halogenation of N-aroyl-2,6(3,5)-dimethyl-1,4-benzoquinone imines we found the halogenation of methyl groups to occur. The bromination of N-aroyl-2,6-dimethyl-1,4-benzoquinone imines yielded 3,6-dibromo-2,6-dimethyl-5-aroyloxycyclohex-2-ene-1,4-diones due to the strong acceptor property of the ArCO group and high redox potentials of N-aroyl derivatives. In the chlorination of N-aroyl-3,5-dimethyl-1,4-benzoquinone imines the chlorine addition to the C=C bond of the quinoid ring proceeded both by the trans- and syn-scheme.     

1,6-Conjugate addition of C-nucleophiles to p-quinone methide surrogate: Synthesis of diarylpropanes

1,6-Conjugate addition of various carbon nucleophiles to p-quinone methide surrogate is reported. The active methylene containing C-nucleophiles such as 1,3-diketones, diesters and ketoesters underwent two consecutive additions leading to bis-addition products, diarylpropanes. Whereas, nitroalkanes proceeded to contribute mono-addition products. Surprisingly, bromo analogue of p-quinone methide surrogate underwent halophilic dimerization reaction with excellent yield. The reported strategy provides an efficient synthesis of 1,3-diarylpropane derivatives bearing pharmacophoric ortho-methoxy phenol moiety under mild reaction conditions.     

A new regio- and stereoselective intermolecular Friedel-Crafts alkylation of phenolic substrates with aryl epoxides

A conceptually new regioselective and highly syn-stereoselective intermolecular Friedel-Crafts-type O-alkylation of phenols with aryl epoxides by the use of appropriately substituted aryl borates is reported. The carbon-carbon bond formation occurs in neutral and mild conditions without the need for external Lewis acids or transition metal catalysts.     

Acid-catalyzed addition of indoles to hydroxyquinones

Hydroxyquinones react smoothly with substituted indoles in the presence of a catalytic amount of p-toluenesulfonic acid to afford a variety of addition products. The main products are either the corresponding p-quinone or the corresponding hydroquinone, resorcinol and benzenetriol mono- and diindolyl derivatives, depending on the nature of the hydroxyquinone and the substituents on the indole ring.     

Highly chemoselective synthesis of aryl allylic sulfoxides through calcium hypobromite oxidation of aryl allylic sulfides

A highly chemoselective oxidation of widely substituted aryl allylic sulfides, prepared by allylation of arylthioethers with KF-Celite, to the corresponding aryl allylic sulfoxide was achieved by employing calcium hypobromite. Neither over-oxidation to sulfones nor halogenation of the aromatic rings was observed. The protocol may be successfully applied for the oxidation of substituted allylic systems (i.e., 2-haloallyl) that per se could interact with the oxidizing agent.     

Diastereofacial selectivity in aldol-type condensation induced by optically pure α-sulfinyl acetate with α-substituted aldehydes

Highly diastereoselective aldol-type condensations induced by the chiral magnesium enolate of tert-butyl p-tolyl sulfinyl acetate were performed with optically pure alkyl or hydroxy α-substituted aldehydes. The addition of chiral α-sulfinyl acetate to various aldehydes, α-substituted or not, results mainly with a syn stereochemistry of the two newly created stereocenters. Applications were investigated for the synthesis of syn and trans 1,2-diol models and polysubstituted precursor for natural products.     

Silver-catalyzed decarboxylative halogenation of carboxylic acids

Decarboxylative halogenation of carboxylic acids catalyzed by silver carbonate is reported. ortho-Nitrobenzoic acids react with copper(II) chloride or bromide in DMF/DMSO at 130-140 °C leading to the corresponding aryl halides in moderate to good yields.     

Stereoselective allylation of α-hydroxy aldimines and its application to the formal synthesis of (−)-β-conhydrine

Stereoselective allylation of N-p-methoxyphenyl (PMP)-substituted α-hydroxy aldimines is described. Several Lewis acids (BF₃·OEt₂, SnCl₄, TiCl₄, ZnCl₂, and MgBr₂·OEt₂) were employed to mediate the allylation reactions. The addition of the allyl group generates a new stereocenter and affords the syn vicinal amino alcohol. Formal synthesis of (?)-β-conhydrine (1) was accomplished via syn-selective allyl addition to N-PMP-substituted α-hydroxy aldimine.