Pd catalyzed coupling of 1,2-dibromoarenes and anilines: formation of N,N-diaryl-o-phenylenediamines

1,2-Dibromoarenes were coupled with aniline derivatives to yield N,N-diaryl-o-phenylenediamines in moderate to good yield using a palladium/phosphine or palladium/carbene catalyst system. Under similar conditions, 1,2,4,5-tetrabromobenzene was coupled with aniline derivatives to produce the corresponding tetrasubstituted derivatives which are oxidized on workup to yield azophenines. The sequential reaction of two different anilines with 1-chloro-2-iodobenzene afforded mixed N,N-diaryl-o-phenylenediamines.     

Helicity of N,N′-diaryl-trans-1,2-diaminocyclohexane derivatives. Implications for molecular helicity manipulations

Derivatives of trans-1,2-diaminocyclohexane (DACH), useful as chiral ligands, scaffolds and building blocks, differ in their conformation. The conformation of N,N′-diaryl-DACH derivatives was studied by the semiempirical and DFT computational methods and by exciton-coupled circular dichroism. It was found that, contrary to M-helical N,N′-diimine, N,N′-diimide and N,N′-diamide derivatives, the aromatic residues in N,N′-diphenyl derivatives are oriented to form a P-helix for the (R,R)-DACH absolute configuration. The helicity of the bis-aryl system is modified in the case of 1-naphthyl or 2-naphthyl derivatives. Further switching of helicity has been demonstrated by either protonation or mono-N-acetylation of N,N′-diaryl DACH derivatives.     

Unprecedented InCl3-catalyzed formation of cis-fused perhydrofuro[2,3-b]oxepines

2-Methylindole and its N-substituted derivatives react smoothly with 2,3-dihydrofuran (DHF) in the presence of a catalytic amount of InCl₃ under mild conditions to afford the corresponding 2-methyl-3-perhydrofuro[2,3-b]oxepin-4-yl-1H-indole derivatives in fairly good yields with high diastereoselectivity, while 3,4-dihydro-2H-pyran (DHP) affords exclusively 5,5-di(1H-3-indolyl)-1-pentanol derivatives in high yields under similar reaction conditions.     

An efficient synthesis of ortho-N-Boc-arylmethyl ketone derivatives

A new and efficient method for the preparation of ortho-N-Boc-arylmethyl ketone derivatives is reported. The reaction involves the intermediacy of a 4-methylene-3,1-benzoaxin-2-one moiety which smoothly converts to the target compounds under acidic conditions. The ortho-N-Boc-arylmethyl ketone derivatives can be formed in a one-pot reaction or alternatively the 4-methylene-3,1-benzoaxin-2-ones can be isolated and subsequently transformed into the desired products.     

Synthesis, luminescence properties, and theoretical insights of N-alkyl- or N,N-dialkyl-pyrene-1-carboxamide

We report the synthesis and photophysical properties of N-alkyl- or N,N-dialkyl-pyrene-1-carboxamide. These derivatives, as well as pyrene, exhibited blue emission. N-Alkyl-type derivatives exhibited strong fluorescence emission (Φ_fl = 0.61 in EtOH) in both nonpolar and polar solvents. On the other hand, N,N-dialkyl-type derivatives showed weak fluorescence emission (Φ_fl <0.01) due to vibrational deactivation. However, in highly viscous solvents such as glycerin, the quantum efficiencies of N-alkyl-type (Φ_fl = 0.91) and N,N-dialkyl-type (Φ_fl = 0.082) derivatives were increased. We also investigated the fluorescence mechanism of these compounds using time-dependent density-functional theory (TD-DFT). From these results, we find that highly fluorescent pyrene-1-carboxamide derivatives can be designed by introducing an appropriate functional group at the nitrogen atom of the amide. Thus, N,N-dialkyl-type pyrene-1-carboxamide has considerable potential for use in applications such as environmental response sensors and probes.     

Synthesis of 1H-pyrazolo[3,4-d]pyrimidines via solid-phase Aza-Wittig/electrocyclic ring closure reaction

An elegant solid-phase synthetic route of pyrazolo[3,4-d]pyrimidine derivatives via Aza-Wittig/electrocyclic ring closure reaction was developed and validated. By manipulating the R group from the primary amine building block, one can easily prepare the library of pyrazolo[3,4-d]pyrimidine derivatives.     

6-endo Versus 5-exo radical cyclization: streamlined syntheses of carbahexopyranoses and derivatives by 6-endo-trig radical cyclization

Three factors that can direct 6-endo radical cyclization over 5-exo ring closure: substitution at C-5, vinyl radical cyclization and ring strain, have been considered in the context of the preparation of carbapyranoses from carbohydrate derivatives. As a result, alkyl radicals in substrates containing a strain inducing 2,3-O-isopropylidene ring, and vinyl radical in non-strained compounds undergo a completely regioselective 6-endo-trig ring closure leading to carbasugar derivatives.     

Efficient preparation of (Z)-alkenyl derivatives from (Z)-vinyl (N,N-diisopropyl)carbamate via Ni-catalysed coupling reactions

A (Z)-vinyl (N,N-diisopropyl)carbamate treated with Grignard reagents, under Wenkert Nickel-catalysed conditions, gave access to several substituted (Z)-alkenyl derivatives. These Nickel-catalysed reactions, carried out with vinyl-, phenyl-, p-methoxyphenyl-, trimethylsilylmethylmagnesium bromide and benzylmagnesium chloride, led to the corresponding (Z)-alkenyl derivatives in good yields and high stereoselectivities.     

New B-substituted derivatives of m-carborane, p-carborane, and cobalt bis(1,2-dicarbollide) anion

The Pd-catalyzed cross-coupling reactions of B-I bond in m- and p-carboranes and cobalt bis(1,2-dicarbollide) anion with organomagnesium and organozinc compounds were studied. Carboranyl derivatives of furan, thiophene, indole, pyridine and quinoline were synthesized. 2-Pyridylethynyl and 3-quinolylethynyl derivatives of p-carborane were prepared by Pd-catalyzed cross-coupling reactions using corresponding alkynes or their magnesium derivatives.     

Stille reaction over cis-halocyclohexadienediol derivatives

Stille reaction was performed with several halo cis-diol derivatives by reaction with allyltributyltin in the presence of a palladium catalyst forming allyl cis-dihydrodiol derivatives. These couplings were conducted with conventional heating as well as with microwave irradiation. Allylbenzene cis-dihydrodiol was obtained with excellent yield using mild conventional heating. However, if the diol moiety is protected with the isopropylidene group, the expected product is obtained only under microwave irradiation. The unusual reactivity observed for the polyoxygenated derivatives suggests assistance of the free hydroxyls in the catalytic cycle.     

Chemoselective deprotection and functional group interconversion of ring-fused 2N,3O-oxazolidinones of N-acetyl-d-glucosamine

These studies describe the chemoselective deprotection of trans-fused 2N,3O-oxazolidinone derivatives of N-acetyl-β-d-glucosamine. Selective opening of the oxazolidinone ring or N-deacetylation without ring opening is demonstrated. Certain amines are shown to efficiently afford C-2 ureido sugars under mild conditions. This work demonstrates the high degree of chemoselective manipulation possible with ring-fused 2N,3O-oxazolidinone derivatives of N-acetyl-d-glucosamine.     

Chiral 2-C-methylene glycosides and carbohydrate-derived pyrano[2,3-b][1]benzopyrans: synthesis via InCl3 catalyzed stereoselective Ferrier rearrangement of 2-C-acetoxymethyl glycal derivatives

2-C-Acetoxymethyl glycal derivatives react with aliphatic alcohols in the presence of InCl₃ (30 mol %) to furnish the corresponding 2-C-methylene glycosides in excellent yields and with exclusive α-selectivity except for the methyl 2-C-methylene glycosides, which are formed in ∼2:1 anomeric ratio in favour of the α-anomer. The reaction of 2-C-acetoxyglycals with phenols, however, produces the corresponding chiral carbohydrate-derived pyranobenzopyran derivatives via initial Ferrier rearrangement followed by tandem cyclization in excellent yields and moderate to high stereoselectivities in favour of the corresponding 10a-R-pyrano[2,3-b][1]benzopyran derivatives.     

Regioselective synthesis of flavone derivatives via DMAP-catalyzed cyclization of o-alkynoylphenols

A catalytic amount of DMAP promoted cyclization of o-alkynoylphenols via a 6-endo cyclization mode leading to flavone derivatives in high yields without forming 5-exo cyclized aurone derivatives. Utilizing this method, methoxy substituted flavone and alkyl substituted γ-benzopyranone derivatives were synthesized.     

Efficient syntheses of optically pure chiro- and allo-inositol derivatives, azidocyclitols and aminocyclitols from myo-inositol

Efficient routes for the syntheses of optically pure and hitherto unknown l-chiro- and d-allo-inositol derivatives, azido- and aminocyclitols of l-chiro-configuration, diazido- and diaminocyclitols of d-allo-configuration from economically viable myo-inositol are described. These routes provide access to synthetically flexible 1,2:4,5-di-O-isopropylidene-chiro-inositol and 1,6:3,4-di-O-isopropylidene-allo-inositol, which are otherwise difficult to synthesize directly from their parent inositols. A one pot methodology that allows rapid access to both chiro- and allo-inositol derivatives has also been developed. Investigations on the glycosidase inhibitory properties of these novel azido- and amino-inositols unraveled the potentials of these classes of compounds as novel class of glycosidase inhibitors. Both d and l forms of these cyclitols could be synthesized from myo-inositol in gram scales and hence by exploiting the difference in reactivities of cis- and trans-ketals, a variety of protected derivatives, which are useful for the synthesis of unnatural phosphoinositols and natural products, can be synthesized.     

Appending aromatic moieties at the para- and meta-position of calixarene phenol rings via p-bromodienone route

The silver-mediated nucleophilic substitution on calixarene p-bromodienone derivatives (the ‘p-bromodienone route’) with activated aromatic substrates allows the introduction of aromatic moieties at the para- or meta-position of calixarene aromatic rings. Less reactive substrates mainly afford C-O para-coupled derivatives, while more activated ones mainly give inherently chiral, C-C meta-coupled products through a dienone-phenol rearrangement of the intermediate dienone derivative. Examples of C-C para-coupling and O-C coupling at the endo calixarene oxygen atom were also observed.     

A novel and efficient synthesis of pyrimido[4,5-d]pyrimidine-2,4,7-trione and pyrido[2,3-d:6,5-d] dipyrimidine-2,4,6,8-tetrone derivatives

An efficient and direct procedure for the synthesis of pyrimido[4,5-d]pyrimidine-2,4,7-trione derivatives has been described under microwave-assisted conditions. Reaction of 6-amino-1,3-dimethyluracil with aromatic aldehydes resulted in the formation of pyrido[2,3-d:6,5-d] dipyrimidine-2,4,6,8-tetrone derivatives.     

An efficient synthesis of dehydroamino acids and dehydropeptides from O-Cbz and O-Eoc derivatives of serine and threonine

A simple and efficient method for the synthesis of dehydroamino acids from serine and threonine is reported. Various O-Cbz and O-Eoc derivatives of serine and threonine are prepared using CbzCl and EocCl, respectively, and are subjected to an anti-selective elimination on treatment with K₂CO₃ in DMF at 65 °C to afford dehydroalanine and dehydroamino butyric acid derivatives, respectively, in excellent yields. The high stability of these carbonate derivatives of serine and threonine allows their use in normal peptide synthesis as protected serine and threonine residues. Peptides synthesized by incorporating O-Cbz or O-Eoc derivatives undergo ready elimination under the reported conditions, to give the corresponding dehydropeptides in excellent yields. The reaction conditions are mild enough not to cause the racemization of other stereogenic centers present in the peptide.     

Concise semisynthesis of novel phenazine-vitamin E hybrids via regioselective tocopheryl ortho-quinone formation

A regioselective method for the semisynthesis of phenazine derivatives has been disclosed through an efficient IBX mediated ortho-quinone formation from vitamin E derivatives. High chemo- and regio-selectivity was observed during the oxidation step and the corresponding 5,6-ortho-quinones could react with various phenylenediamines. Thus, this methodology proves its interest as a concise semisynthetic pathway to phenazine-vitamin E hybrids with moderate to good yields.     

Metal-free oxidative arylphosphination of activated N-substituted-N-arylacrylamide derivatives using K2S2O8

A novel metal-free oxidative arylphosphination of activated N-substituted-N-arylacrylamide derivatives by phosphorylation and C–H functionalization cascade process has been developed. This methodology provides an efficient way to construct a variety of phosphorus-containing oxindole moieties.     

LiClO4- or LiOTf-accelerated 1,3-dipolar cycloaddition reactions: a facile synthesis of cis-fused chromano[4,3-c]isoxazoles

Acetonitrile solutions of lithium perchlorate or lithium triflate are found to accelerate considerably the intramolecular 1,3-dipolar cycloaddition reactions of nitrones derived in situ from hydroxylamines and the O-prenyl derivatives of salicylaldehydes to afford enhanced rates and improved yields of tetrahydrochromano[4,3-c]isoxazole derivatives with high diastereoselectivity. The stereochemistry of the products has been assigned by using extensive NMR studies.