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ortho-Quinone methides, very reactive transient intermediates, are utilized successfully in synthesizing complex organic molecules of natural and biological significance. Among several synthetic protocols, the acid catalyzed generation of ortho-quinone methides from suitably substituted phenols is a promising method for further exploitation in organic synthesis. Such an interesting reactive species is conveniently employed in the synthesis of conformationally restricted triarylmethane derivatives such as 12/9-arylxanthenes/arylthioxanthenes starting from symmetrical/unsymmetrical 2-(hydroxydiarylmethyl)phenol/thiophenol, respectively, using SiO2–NaHSO4. Conformationally restricted 12/9-arylxanthenes/arylthioxanthenes were obtained in 52 to 96% yields using this protocol, which is believed to involve the formation of o-quinone methides followed by electrocyclic ring closure and isomerization at elevated temperature. Photophysical studies of selected examples in acidic media showed turn-on fluorescence by hydride ion transfer mediated π-conjugated xanthylium salt formation and suggested the application potential in bio-imaging and fluorescent sensors.

Niobium pentoxide, a bifunctional solid surface catalyst, has been successfully employed to facilitate the three-component reaction between aldehydes, amines and triethyl phosphite at room temperature under solvent-free conditions to generate α-amino phosphonate in moderate to good yields. The catalyst can be recycled through simple filtration and reused to effect this transformation.

ortho-Quinone methides, very reactive transient intermediates, are utilized successfully in synthesizing complex organic molecules of natural and biological significance. Among several synthetic protocols, the acid catalyzed generation of ortho-quinone methides from suitably substituted phenols is a promising method for further exploitation in organic synthesis. Such an interesting reactive species is conveniently employed in the synthesis of conformationally restricted triarylmethane derivatives such as 12/9-arylxanthenes/arylthioxanthenes starting from symmetrical/unsymmetrical 2-(hydroxydiarylmethyl)phenol/thiophenol, respectively, using SiO2-NaHSO4. Conformationally restricted 12/9-arylxanthenes/arylthioxanthenes were obtained in 52 to 96% yields using this protocol, which is believed to involve the formation of o-quinone methides followed by electrocyclic ring closure and isomerization at elevated temperature. Photophysical studies of selected examples in acidic media showed turn-on fluorescence by hydride ion transfer mediated π-conjugated xanthylium salt formation and suggested the application potential in bio-imaging and fluorescent sensors.

A conformationally rigid chiral bicyclic skeleton tethered bipyridine–Zn(OTf)2 complex facilitated the enantioselective Friedel–Crafts alkylation of indoles with trans-β-nitroarylalkenes in an enantioselective manner at elevated temperature. Indoles reacted smoothly with β-nitroarylalkenes to generate the corresponding 3-(2-nitroalkyl)indoles in good to excellent yields (up to 94%) with moderate to excellent enantioselectivities (up to 91%). The stereochemical outcome of the product from indole and trans-β-nitrostyrene in the presence of the CRCB tethered bipyridine–Zn(OTf)2 complex and the DFT calculation of the CRCB tethered bipyridine–Zn:trans-β-nitrostyrene complex support the si-face attack of indole on trans-β-nitrostyrene.

Allylation of 2-aminophenol-derived aldimines using allyltrichlorosilane under catalyst free conditions has been developed. This reaction afforded the corresponding homoallylic amines in good to excellent yields (68–94%). The salicylaldehyde-derived aldimines as well as benzoylhydrazone also found to react with allyltrichlorosilane smoothly under the same conditions, to furnish the corresponding homoallylic amine derivatives. This study suggests that the phenolic –OH group acts as an anchoring group for the transfer of allyl group from allyl silane reagent.

A simple and an efficient method for the synthesis of 7-arylfluorenes by intramolecular cyclization of the corresponding triarylcarbinols in the presence of the solid-acid catalyst NaHSO4/SiO2 has been developed. By using this method, a new chiral diol with a C 2-symmetric bisfluorenyl unit, 7,7′-diphenyl-7H,7′H-5,5′-bibenzo[c]fluorene-6,6′-diol (BIFOL), having central chirality was synthesized in an optically active form from (S)-(–)-BINOL-3,3′-dicarboxylic acid. The absolute configuration of the chiral bisfluorene derivative BIFOL was ascertained by single-crystal X-ray analysis. Furthermore, a new chiral phosphoric acid was synthesized from BIFOL and evaluated for enantioselective transfer hydrogenation.

A facile and convenient method for the synthesis of substituted 2-(isoquinolin-1-yl)benzoic acids from isoindoloisoquinolinones in the presence of molecular iodine under sealed tube condition at 100 $$^{\circ }\hbox {C}$$ has been developed. This methodology involves the oxidative dehydrogenation and ring opening of hydroxy lactam/methoxy lactam to furnish the 2-(isoquinolin-1-yl)benzoic acids. Some of these acids are successfully cyclized to furnish the azabenzanthrone derivatives, the potential precursors for the synthesis of menisporphine alkaloids and daurioxoisoaporphines. SYNOPSIS Metal-free synthesis of 1-aryl isoquinolines, which are synthetic precursors for azabenzanthrones or menisporphines, from isoindoloisoquinolinones using iodine under sealed tube conditions is reported. This methodology is successfully utilized to synthesize the 1-azabenzanthrone and analogue of menisporphine, i.e., 5-methoxy-6-hydroxy-1-azabenzanthrone.

A conformationally rigid chiral molecule LB-I with Lewis basic site has been designed and synthesized in racemic form from ferrocene via Lewis acid mediated diastereoselective cyclization of hydroxy lactam. Both isomers were successfully obtained in enantiomerically pure form through classical resolution using dibenzoyl- d -tartaric acid as the chiral resolving agent in acetone. The nature of the diastereomeric salt formed in the resolution process was investigated by single crystal X-ray crystallographic studies. The absolute configuration of (+)-LB-I was unambiguously assigned as (S,Rp) by single crystal analysis of the salt I obtained from precipitate fraction containing (+)-LB-I and dibenzoyl- d -tartaric acid.

A conformationally rigid chiral bicyclic skeleton tethered bipyridine-Zn(OTf)2 complex facilitated the enantioselective Friedel-Crafts alkylation of indoles with trans-β-nitroarylalkenes in an enantioselective manner at elevated temperature. Indoles reacted smoothly with β-nitroarylalkenes to generate the corresponding 3-(2-nitroalkyl)indoles in good to excellent yields (up to 94%) with moderate to excellent enantioselectivities (up to 91%). The stereochemical outcome of the product from indole and trans-β-nitrostyrene in the presence of the CRCB tethered bipyridine-Zn(OTf)2 complex and the DFT calculation of the CRCB tethered bipyridine-Zn:trans-β-nitrostyrene complex support the si-face attack of indole on trans-β-nitrostyrene.

The regio and diastereoselective synthesis of 1 or 2 alkyl-substituted pyrroloisoquinolinones and indolizinoindolones by triflic acid mediated cyclization via an electrophilic activation of unsymmetrical succinimide carbonyl groups followed by the reduction of fused cyclic N-acyliminium ion is reported. This strategy successfully furnished the pyrroloisoquinolinone and indolizinoindolone derivatives in regio- and diastereoselective manner. The steric factor dictates the regioselectivity in N-phenethyl unsymmetrical succinimides and electronic factor seems to dictate the regioselectivity in N-(3-indolylethyl) unsymmetrical succinimides.

A facile and straightforward synthesis of unsymmetrical triarylmethanes and stereogenic methanes have been realized through the Friedel-Crafts type alkylation of arenes with alkoxyaluminium intermediate generated in situ from aldehyde, arene and AlBr3 at room temperature in presence of catalytic quantity of AlBr3. This protocol is successful with diversity of starting materials and desired products were obtained in moderate to good yields. The displacement of -OAlBr2 with catalytic quantity of AlBr3 generated the reactive carbocation like intermediate which underwent subsequent reaction with another nucleophile (either -C, -S or –O nucleophile) and furnished the corresponding substituted products. The mechanism of the controlled, sequential reaction has been investigated by density functional theory calculations. Our model suggests that the involvement of penta coordinate complex in which the cleavage of C−OAlBr2 bond is favoured over N−AlBr2 bond at room temperature, in presence of additional catalyst.

A simple and efficient method has been developed to resolve (±)-2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxylic acid [(±)-BINOL-3,3′-dicarboxylic acid] (±)-1 using inexpensive and readily accessible chiral resolving agent (1R,2R)-trans-cyclohexane-1,2-diamine 2. Enantiomers of BINOL-3,3′-dicarboxylic acid were obtained in good yields and enantiomeric purity, for example, (S)-(−)-1 was isolated in 34% yield with >99% ee and (R)-(+)-1 was obtained in 36% yield with >99% ee. The formation of diastereomeric salt A between (S)-BINOL-3,3′-dicarboxylic acid and (1R,2R)-trans-cyclohexane-1,2-diamine was ascertained by using IR, single crystal X-ray crystallography, and HRMS.

The fused cyclic N-acyliminium ion generated during the imide carbonyl activation reaction of phenethylphthalimide was confirmed by single crystal X-ray diffraction. The Lewis acid assisted imide carbonyl activation methodology was successfully extended to synthesize fused tetrahydro-β-carboline units from the corresponding N-indolylethylimides.

Isoquinoline-based polycyclic lactams such as isoindoloisoquinolinones, pyrroloisoquinolinones, and benzo[a]quinolizinones were successfully assembled from the corresponding imides by using a TfOH-mediated (TfOH = trifluoromethanesulfonic acid) imide carbonyl activation and cyclization strategy. By employing this simple method, the isoquinoline alkaloids crispine A, trolline/oleracein E, and erythrinarbine were successfully synthesized in racemic form. The reaction of unsymmetrical N-phenethylphthalimides with TfOH displayed excellent regioselectivity, which was rationalized by DFT calculations.

A series of novel fused isoquinolinones with isoindoloisoquinolinone, pyroloisoquinolinone, and benzoquinalizinone skeletons were synthesized from corresponding phenethylimides. The isoquinolinone derivatives were evaluated for their protective effect on chicken erythrocytes subjected to oxidative damage. The effect of isoquinolinone derivatives were analysed by estimation of cell viability, antioxidant enzyme activities, DNA damage (comet assay), PARP-1 inhibition assay and molecular docking of the compounds with PARP-1 active site. The compounds CRR - 271 , CRR - 288 and CRR - 224 + 225 showed significant protective effect at 100 μM concentration. The PARP-1 inhibition assay revealed the IC 50 values of CRR - 271 , CRR - 288 and CRR - 224 + 225 as

The conformationally rigid chiral bicyclic skeleton tethered bipyridine N,N′-dioxide (−)-9 has been designed, synthesized and examined as an organocatalyst in the enantioselective ring opening of meso-epoxides using tetrachlorosilane (SiCl4). The catalyst (−)-9 is found to exhibit good enantioselectivity for substituted cis-stilbene epoxides; whereas, the saturated cyclic meso-epoxides display a moderate enantioselectivity. At −30 °C in chloroform, the catalyst (−)-9 with 0.5 mol % loading generated the chlorohydrins in up to 97 % yield with up to 93 % ee. The possible creation of transient axial chiral environment around hypervalent silicon species due to the presence of conformationally rigid chiral bicyclic skeleton tethered bipyridine N,N′-dioxide may be responsible for such enantioselectivity observed in the desymmetrization of meso-epoxides.

A pyridine unit with a conformationally rigid chiral backbone has been designed and synthesized in an enantiomerically pure form to utilize in the Lewis base-catalyzed Sakurai–Hosomi–Denmark-type allylation reaction. The chiral pyridine N-oxide in 1:1 mixture of chloroform and 1,1,2,2-tetrachloroethane produced the homoallylic alcohols in up to 98% yield and up to 94% ee.

The conformationally rigid chiral ligand, trans -12-(pyridin-2-yl)-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid ethyl ester, 1 , was designed and synthesized in racemic form. Both isomers were successfully obtained in enantiomerically pure form through classical resolution using l -(+)-tartaric acid in acetonitrile . The nature of the diastereomeric complex formed in this resolution was elucidated using single crystal X-ray crystallographic studies. The absolute configuration of (+)- 1 was unambiguously assigned as (11 S ,12 S ) by single crystal structural analysis of salt 5 formed from (+)- 1 and l -(+)-tartaric acid.

Racemic erythrinarbine (IVb) and further tricyclic lactams (II) and (IV) are readily prepared via a TfOH-mediated cyclization reaction.

The involvement of brain monoamine systems in the discriminative stimulus effects of methamphetamine (MA) was studied in squirrel monkeys by evaluating the effects of differentially selective monoamine uptake inhibitors alone and in combination. In monkeys discriminating i.m. injections of 0.3 mg/kg MA from saline, methamphetamine (0.01-0.3 mg/kg), and dopamine transporter (DAT) inhibitors, including 1-[2-(bis(4-fluorophenyl)-methoxy)ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909; 1.0-17.8 mg/kg) and its analogs AM2502 (1.0-17.8 mg/kg), AM2506 (1.0-30.0 mg/kg), AM2515 (1.0-17.8 mg/kg), and AM2517 (1.0-5.6 mg/kg), produced dose-related increases in responding on the MA-associated lever and, at the highest doses, full substitution. The time course of MA-like effects was similar for equivalent (3.0 mg/kg) doses of GBR 12909 and its most potent analog, AM2517. Unlike the DAT blockers, the selective 5-hydroxytryptamine (serotonin) uptake inhibitor clomipramine (1.0-10.0 mg/kg) and the selective norepinepherine (NE) uptake inhibitor desipramine (1.0-10 mg/kg) produced responding primarily on the saline lever. The selective NE uptake inhibitor nisoxetine partially substituted at the highest dose tested (10.0 mg/kg). Pretreatment with GBR 12909 or AM2517 enhanced the discriminative stimulus effects of MA, shifting the dose-effect curve leftward. The NE uptake inhibitors desipramine or nisoxetine also enhanced the discriminative stimulus effects of MA, whereas clomipramine only attenuated them. These results support the view that dopaminergic mechanisms play a prominent role in the discriminative stimulus effects of MA in monkeys, whereas involvement of serotonergic and noradrenergic systems may be limited to a modulatory role.

An efficient C–C bond formation strategy between aromatic/heteroaromatic π-nucleophiles and Lewis acid activated aldehydes is described. This aromatic electrophilic substitution reaction of arenes or heteroarenes is facilitated by Lewis acid AlBr3. Aromatic rings with electron donating substituents are excellent nucleophilic counterparts in this reaction, generating carbinols in excellent yields (61–94%). The formation of triarylmethanes is also witnessed in the case of certain reactive aldehydes and aromatic π-nucleophiles through reactive carbocation formation. The formation of triarylmethane is reduced to a greater extent via retardation of the second π-nucleophile addition through a Lewis base, for example, pyridine, coordination with an aluminium alkoxide intermediate. Various aliphatic aldehydes also underwent Friedel–Crafts type hydroxyalkylation and generated the expected carbinols in moderate yields (41–53%) in the presence of AlBr3. This protocol has been successfully applied to the synthesize of the (±)-carbinoxamine, a therapeutically important histamine H1 antagonist, in a one-pot manner.

The conformationally rigid chiral bicyclic skeleton tethered bipyridine N,N′-dioxide (−)-9 has been designed, synthesized and examined as an organocatalyst in the enantioselective ring opening of meso-epoxides using tetrachlorosilane (SiCl4). The catalyst (−)-9 is found to exhibit good enantioselectivity for substituted cis-stilbene epoxides; whereas, the saturated cyclic meso-epoxides display a moderate enantioselectivity. At −30 °C in chloroform, the catalyst (−)-9 with 0.5 mol % loading generated the chlorohydrins in up to 97 % yield with up to 93 % ee. The possible creation of transient axial chiral environment around hypervalent silicon species due to the presence of conformationally rigid chiral bicyclic skeleton tethered bipyridine N,N′-dioxide may be responsible for such enantioselectivity observed in the desymmetrization of meso-epoxides.

Aromatic electrophilic substitution of aromatic/electron rich heteroaromatic compounds with AlBr3 activated aldehydes/ketone to afford pyridyl aryl/heteroaryl or diaryl carbinols is described. The strong electron donating group dictates the regiochemical outcome of the product.

Among various derivatives tested, N-oxide (I) is found to be optimal for the process which is applied to a wide range of aromatic and aliphatic aldehydes.

The intramolecular cyclization of phenethylphthalimides (I) and (IV) gives a fused isoindoloisoquinolinone skeleton.

Activation of imide carbonyl group with trifluoromethanesulfonic acid facilitates the intramolecular cyclization of phenethylphthalimides to give a fused isoindoloisoquinolinone skeleton. The first one pot regioselective synthesis of isoindoloisoquinolinone alkaloid (±)-nuevamine has been successfully executed using this methodology.

A simple methodology to construct the tetrahydroisoquinoline containing skeleton through electrophilic activation of imide carbonyl group of N-phenethylimides using BBr3 as Lewis acid is developed.

Resolution of the racemic amino alcohol derivatives 1-6 is readily achieved to obtain enantiomerically enriched compounds using chiral 1,1'-bi-2-naphthol and boric acid in solvents such as CH(3)CN, THF, and MeOH. Purification of the diastereomeric mixture 7 has also been carried out following this method. The corresponding intermediate ammonium borate complexes were also characterized by X-ray diffraction methods.

Aromatic electrophilic substitution of aromatic/electron rich heteroaromatic compounds with AlBr3 activated aldehydes/ketone to afford pyridyl aryl/heteroaryl or diaryl carbinols is described. The strong electron donating group dictates the regiochemical outcome of the product.

Indole, a π-nucleophile, reacts with Bronsted acid activated imide carbonyl group in an intramolecular fashion via a 6-exo-trig cyclization, to deliver a condensed tetrahydro-β-carboline unit. This methodology is effectively applied to assemble the tetrahydro-β-carboline skeleton containing alkaloids such as harmicine and 10-desbromoarborescidine-A.

Isoindoloisoquinalinone, pyrroloisoquinolinone and benzo[a]quinolizinone units are constructed via intramolecular cyclization of the methoxy substituted N-phenethylimides using BBr(3).