Substituent directed regioselective synthesis of 2-oxonicotonic acids and methyl nicotinates

An innovative synthesis of aryl tethered 1,2-dihydro-2-oxopyridine-3-carboxylic acids has been developed through nucleophile induced ring transformation of methyl 6-aryl-4-methylsulfanyl-2H-pyran-2-one-3-carboxylates using either cyanamide or arylamidine in excellent yields. Further, the reaction of methyl 6-aryl-4-methylsulfanyl-2H-pyran-2-one-3-carboxylates with formamidine acetate under analogous reaction conditions did not follow the same course of reaction and produced methyl nicotinate, regioselectively, in good yield. Decarboxylation of a 6-aryl-4-methylsulfanyl-1,2-dihydro-2-oxopyridine-3-carboxylic acid has been achieved by heating in PPA. The 4-methylsulfanyl substituent in 3 has also been oxidized to the corresponding methylsulfonyl group with m-chloroperbenzoic acid.     

A regioselective synthesis of aryl substituted arylacetates through ring transformation by ethyl levulinate

A regioselective synthesis of sterically hindered ethyl arylacetates in one step through ring transformation of suitably functionalized 6-aryl-3,4-disubstituted-2H-pyran-2-ones with ethyl levulinate at room temperature in excellent yields is described.     

A non-catalytic regioselective approach to the synthesis of (E)-stilbenes from suitably functionalized 2H-pyran-2-ones

Highly functionalized (E)-stilbenes 3a-m and 4-aryl-6-styryl-pyran-2-ylidineacetonitriles 4a-b have been prepared and delineated through the ring transformation of 6-aryl-3,4-disubstituted-2H-pyran-2-ones 1 with commercially available (E/Z)-4-phenyl-3-buten-2-one 2 without the use of any catalyst.     

An efficient substituent dependent synthesis of congested pyridines and pyrimidines

An efficient and versatile synthesis of various congested pyridines 3a-h, 6a,b, 8a-n, 10a-g, and 16a,b, and (pyrimidin-4-yl)acetonitriles 13a-g has been delineated by base catalyzed ring transformation of suitably functionalized 2H-pyran-2-ones 1a-h, 5, 7, and 15 by formamidine acetate 2a, acetamidine hydrochloride 2b, S-methylisothiourea 9a, pyrazol-1-yl-carboxamidine 9b, and arylamidine hydrochloride 12 separately in the presence of powdered KOH in dry DMF.     

A novel synthesis of aryl tethered imidazo[4,5-b]pyrazin-2-ones through in situ ring construction and contraction

An innovative synthesis of aryl tethered 1,3-dimethylimidazo[4,5-b]pyrazin-2-ones 4 and 6 has been delineated through base catalyzed ring transformation of 6-aryl-4-(piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles 1 and methyl 6-aryl-4-methylsulfanyl-2H-pyran-2-one-3-carboxylates 5 with 7-acetyl-1,3-dimethyllumazine 2 with subsequent ring contraction of the fused pyrimidine to an imidazole ring. An additional product, methyl [6-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)-4-thiophen-2-ylpyran-2-ylidene]acetate 8b, was also isolated from the reaction of 5 and 2, as a minor constituent.     

A novel strategy for the expeditious synthesis of aryl-tethered highly congested 2-hydroxybenzyl alcohols from 2-pyranones

An efficient and simple synthesis of highly congested 2-benzyloxy-3-benzyloxymethyl-5-sec-aminobiphenyl-4-carbonitriles 3a-e has been delineated through base catalyzed ring transformation of 6-aryl-4-sec-amino-2H-pyran-2-one-3-carbonitriles 1 by 1,3-bisbenzyloxypropan-2-one 2. Debenzylation of both the O-benzyl groups of 3a-e with boron trichloride provided the corresponding diols, 2-hydroxy-3-hydroxymethyl -5-sec-aminobiphenyl-4-carbonitriles 4a-e in very good yields.     

A one-pot efficient synthesis of highly functionalized 5,6-dihydronaphthalenes from 2H-pyran-2-one

A one-pot efficient synthesis of highly functionalized 5,6-dihydronaphthalenes has been delineated through carbanion-induced ring transformation of 2H-pyran-2-ones by 2-cyclohexenone.     

An unusual synthesis of tetrahydrobenzo[f]isoquinolines

A facile and short synthesis of 2-oxo-4-sec-amino-2,3,5,6-tetrahydrobenzo[f]isoquinoline-1-carbonitriles has been delineated through base catalyzed ring transformation of 5,6-dihydro-2-oxo-4-sec-amino-2H-benzo[h]chromene-3-carbonitrile by cyanoacetamide in excellent yields.     

A regioselective synthesis of 2,4-dialkyl resorcinols

A general regioselective synthesis of 2,4-dialkyl resorcinols from ethoxymethylenemalonate ethyl ester and dialkyl ketones is reported.     

An efficient non-catalytic, regioselective approach to the synthesis of angularly fused polycyclic systems

A novel approach to the synthesis of partially reduced different ring sizes of PAH analogs with sec.amino and nitrile functionalities is delineated through base-induced ring transformation of 4-sec.amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by a carbanion, generated in situ from cyclopentanone, cyclohexanone, cycloheptanone, and cyclooctanone separately in good yields. An increase in the size of cycloalkanone ring beyond cyclooctanone restricts the ring transformation under analogous reaction conditions possibly due to bulky conformation of higher homologs. The synthetic method provides an efficient general route for the construction of angularly fused partially reduced polycyclic aromatic hydrocarbons: 5-sec.amino-2,3,6,7-tetrahydro-1H-cyclopenta[c]phenanthrene-4-carbonitriles, 6-sec.amino-2,3,4,7,8-pentahydro-1H-benzo[c]phenanthrene-5-carbonitriles, 7-sec.amino-2,3,4,5,8,9-hexahydro-1H-cyclohepta[c]phenanthrene-6-carbonitriles, and 8-sec.amino-2,3,4,5,6,9,10-heptahydro-1H-cycloocta[c]phenanthrene-7-carbonitriles.     

Studies directed toward total synthesis of rhodocomatulins: A regioselective synthesis of brominated hydroxyanthraquinones by anionic annulations

In this work, brominated hydroxyanthraquinones, which are the core structural motif of naturally occurring bromorhodocomatulins, were successfully synthesized using Hauser annulation reaction as the key step. When brominated Michael acceptors (brominated p-quinone monoketals) and cyanophthalides or bromocyanophthalides (Hauser donors) were reacted under the annulation conditions, brominated anthraquinones were obtained with 81–87% yields for four examples. On acidic quenching, products were obtained as solid which were separated by filtration and purified by recrystallization in acetone. No chromatography was required.     

A highly efficient total synthesis of (R)-(+)-muscopyridine by intramolecular [4+2] cycloaddition of bisketene

A highly efficient total synthesis of (R)-(+)-muscopyridine 1 has been accomplished in 12 steps with 40% overall yield. A highlight of the synthesis is the intramolecular [4+2] cycloaddition of bisketene to afford a bridged pyrone and ring transformation of the pyrone to afford pyridine derivatives.     

A facile method for regioselective synthesis of new N-acetyl/thioacetyl-(E)-stilbene benzenesulfonamide derivatives via N-acetyl/thioacetyl sulfonamide formation

A series of new N-acetyl/thioacetyl-(E)-stilbene benzenesulfonamide derivatives were synthesized regioselectively in moderate to high yields by following a convenient, three-step procedure. The procedure consists of the direct oxidative conversion of a thiol compound to the corresponding sulfonyl chloride using TMSCl/KNO₃, followed by a room temperature reaction in a one-pot transformation of the resultant sulfonyl chloride into N-acetyl/thioacetyl sulfonamide, which undergoes a further Pd-catalyzed coupling reaction, giving rise to the stilbene compounds reported for the first time.     

A clay-mediated, regioselective synthesis of 2-(aryl/alkyl)amino-thiazolo[4,5-c]carbazoles

The 3-aminocarbazoles 1a-e were condensed with phenyl and benzyl isothiocyanates on montmorillonite K10 clay or TLC-grade silica gel at room temperature to furnish efficiently the N-phenyl and N-benzylthioureidocarbazoles, 2a-e and 2f, respectively, within minutes. When adsorbed on montmorillonite K10 clay impregnated with para-toluene sulfonic acid (1:1, w/w) and heated at 60-70 °C, 2a-e and 2f furnished the 2-anilino and 2-benzylaminothiazolo[4,5-c]carbazoles, 3a-e and 3f, respectively, regioselectively in high yields. The cyclisation was also effective for the N-methylthioureidocarbazoles 2g-i.     

A novel route for the synthesis of highly congested aryl-tethered 2-aminobenzylamines through ring transformation of 2-pyranones

An innovative and efficient synthesis of highly congested 2-amino-3-aminomethyl-5-methylsulfanyl/sec-aminobiphenyl-4-carbonitriles 4 has been delineated through base catalyzed ring transformation of 6-aryl-4-methylsulfanyl/sec-amino-2H-pyran-2-one-3-carbonitriles 1 with Boc-protected 1,3-diamino-2-propanone 2, followed by TFA catalyzed hydrolysis of the intermediate [3-tert-butoxycarbonylaminomethyl-4-cyano-5-methylsulfanyl/sec-aminobiphenyl-2-yl]carbamic acid tert-butyl ester 3 in moderate yields as the TFA salts.     

An efficient one-pot synthesis of annulated pyridines utilising a directed ortho-metallation/transmetallation approach

The ortho-alkylation of Boc-protected aminopyridines with α,ω-dihaloalkanes followed by in situ cyclisation, resulted in the corresponding annulated pyridine derivatives in good to excellent yields. The effect of the alkylating and chelating agents, the transmetallation additives and the directing group was examined.     

Versatility of 2-oxobenzo[h]chromene for the synthesis of oxabenzo[c]chrysenes

An innovative and concise synthesis of (7,8-dihydro-5-oxabenzo[c]chrysene-6-ylidene)acetonitriles is described through base catalyzed ring transformation of 2-oxo-4-piperidin-1-yl-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 1-tetralone in very good yields.     

Iodocyclization/base-induced hydrodeiodination reaction of 5-substituted 4-alkenols. The influence of substituent on the stereoselective pathway

The electrophilic iodocyclization reaction of (Z)- and (E)-5-n-alkylsubstituted 4-alken-1-ols followed by base-induced hydrodeiodination reaction stereoselectively gave, respectively, (Z)- and (E)-alkylidentetrahydrofurans in high yield. Completely different outcomes were observed with (Z)- and (E)-6,6-dimethylhept-4-en-1-ol: their iodocyclization furnished, respectively, threo- and erythro-2-(1-iodo-2,2-dimetylpropyl)tetrahydrofuran with high stereoselectivity. The threo isomer gave clean formation of 6-tert-butyl-3,4-dihydro-2H-pyran by base-induced ring expansion, while erythro isomer underwent a base-induced ring contraction to 1-cyclopropyl-3,3-dimethylbutan-1-one. Moreover, (Z)- and (E)-5-cyclopropylpent-4-en-1-ol underwent a 6-endo-iodocyclization to threo- and erythro-2-cyclopropyl-3-iodotetrahydro-2H-pyran, respectively, that under the same basic treatment, gave two isomeric 6-cyclopropyldihydro-2H-pyrans in a stereoselective fashion.     

Angular hydroxymethyl directed intramolecular Diels-Alder approach for the stereo- and regioselective synthesis of pimaraditerpenes

The stereo- and regioselective synthetic route to pimaraditerpenes, employing an angular hydroxymethyl directed intramolecular Diels-Alder reaction of the decaline intermediate, has been developed. This synthetic approach allows prompt access to both natural pimaraditerpenes and the unnatural regioisomers, which would be potentially new anti-inflammatory pimaraditerpenes.     

A non-catalytic approach to the synthesis of 5,6-dihydrobenzo[h]quinolines

A concise synthesis of highly functionalized 5,6-dihydrobenzo[h]quinoline-3-carbonitriles is delineated through base induced ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with S-methylisothiourea sulfate and 1-carboxamidinepyrazole hydrochloride, separately, in DMF. Under analogous reaction conditions the ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by formamidine acetate provided 4-sec-amino-benzo[h]quinoline-3-carbonitriles in moderate yields, while with benzamidine hydrochloride, the reaction followed the same mechanism to yield 2-phenyl-4-sec-amino-5,6-dihydrobenzo[h]quinoline-3-carbonitriles.