Asymmetric 1,4-addition of oxazolones to nitroalkenes by bifunctional cinchona alkaloid thiourea organocatalysts: synthesis of alpha,alpha-disubstituted alpha-amino acids

An easy and simple synthetic approach to optically active alpha,alpha-quaternary alpha-amino acids using asymmetric organocatalysis is presented. The addition of oxazolones to nitroalkenes catalyzed by thiourea cinchona derivatives provides the corresponding alpha,alpha-quaternary alpha-amino acid derivatives with good yields, excellent diastereoselectivities (up to 98 % dr), and from moderate to good enantioselectivities (up to 92 % ee). The reaction can be performed on a large scale. The optically active oxazolone-nitroalkene addition products can be opened in a one-pot reaction to the corresponding ester-amide derivatives. Additional transformations are also presented, such as the synthesis of amino esters, amino acids, and transformation into 3,4-disubstituted pyrrolidin-2-ones.     

Chemistry of phosphorus ylides. Part 25 [1]. Interaction of hexaphenylcarbodiphosphorane with carbonyls, hydrazone, and Mannich bases. A synthesis of phosphoranylidenes, phosphobetaines, and oxaphosphinin

The reaction of the allylic hexaphenylcarbodiphosphorane with carbonyls afforded the corresponding phosphoranylidene derivatives. On the other hand, the stable phosphorbetaines were obtained when the bisphosphorane was allowed to react with the α-diketone and triketone. The azaphosphoranylidene was isolated from the reaction of the bisphosphorane with hydrazone. Moreover, the bisphosphorane reacted with niclosamide and quinoline Mannich bases with the formation of the oxaphosphinins. When the Wittig reaction was performed with the new phosphoranes, the corresponding exocyclic olefins were obtained. On the other hand, the oxaphosphinins were produced when the phosphoranes were treated under the condition of a Hoffmann degradation reaction. Correspondence: Medhat M. Said, Department of Organometallic and Organometalloide Chemistry, National Research Centre, El-Tahrir Street, Dokki, Cairo, Egypt.     

Synthesis of quinolines, 2-quinolones, phenanthridines, and 6(5h)-phenanthridinones via palladium[0]-mediated Ullmann cross-coupling of 1-bromo-2-nitroarenes with beta-halo-enals, -enones, or -esters

Palladium[0]-mediated Ullmann cross-coupling of 1-bromo-2-nitrobenzene (1 R = H) and its derivatives with a range of beta-halo-enals, -enones, or -esters readily affords the corresponding beta-aryl derivatives, which are converted into the corresponding quinolines, 2-quinolones, phenanthridines, or 6(5H)-phenanthridinones on reaction with dihydrogen in the presence of Pd on C or with TiCl(3) in aqueous acetone. [reaction: see text]     

N-Alkylation of N-trimethylsilyl derivatives of lactams,amides, and imides with alkyl sulfonates

Russian Chemical Bulletin - The reaction of N-trimethylsilyl derivatives of amides and imides with alkyl sulfonates on heating affords the corresponding N-alkyl derivatives and trimethylsilyl...     

Dapson in Heterocyclic Chemistry,Part II: Antimicrobial and Antitumor Activities of Some Novel Sulfone Biscompounds Containing Biologically Active Thioureido,Carbamothioate, Quinazoline,Imidazolidine, and Thiazole Moieties

The reaction of 4,4′-diisothiocyanato-1,1-diphenylsulfone 2 with aromatic amines and phenol derivatives afforded the corresponding thioureio derivatives 3–9 , respectively. Also, the reaction of 2 with catechol gave the corresponding carbamothioate derivative 11. Quinazoline derivatives 14 and 15 were obtained in good yield via reaction of 2 with anthranlic acid derivatives. Imidazolidine biscompounds 16 and 17 were readily synthesized from the reaction of 2 with N-(4-substituted-phenyl)cyanothioformanilides. The structure of the products was confirmed from elemental analysis as well as spectral data. Most of the synthesized compounds showed remarkable antimicrobial activity compared with chloramphenicol and Grisofluvine as positive controls. Compound 6 was almost as active an antitumor agent as the reference drug Doxorubicin.     

Synthesis of C-Ring Hydroxylated Neoflavonoids by Ligand Coupling Reactions

Reaction of 4-trifluoromethanesulfonyloxycoumarin derivatives with benzyloxyphenylboronic acid derivatives under modified Suzuki reaction conditions afforded the corresponding neoflavones. Selective debenzylation took place in high yields when the palladium-catalysed hydrogenolysis was performed in the presence of acetic acid.     

Reactions of some benzofuran derivatives with amides,nitriles and hydrazines

When 6-acetoacetyl-5-methoxy- ( 1b ) and 5-acetoacetyl-6-methoxy-2,3-diphenylbenzofuran ( 2b ) were treated with cyanoacetamide, the corresponding pyridinecarbonitriles were obtained. Compounds 1b and 2b reacted with ethyl cyanoacetate in the presence of ammonium acetate to give the benzofuranyl-pyrone derivatives. This reaction, when carried out in presence of diethylamine, led to the formation of furochromones. Hydrazine hydrate, phenylhydrazine and semicarbazide hydrochloride reacted with 1b and 2b with the formation of the corresponding pyrazoles. The corresponding isoxazole derivatives were formed by the reaction of 1b and 2b with hydroxylamine hydrochloride.     

Catalytic hydrogen transfer over magnesia, Part XVIII. , Chemoselective reduction of formyl and acetyl derivatives of furan and thiophene

Chemoselective reduction of formyl and acetyl derivatives of furan (F) and thiophene (T) to the corresponding carbinols by 2-propanol has been performed in vapour phase over MgO as a catalyst. Formyl derivatives of (F) and (T) have been reduced to the corresponding carbinols with selectivity 96 and 71%, respectively. Above 573 K the reduction of (T)-CHO was accompanied by the formation of thiophene whose yield increased with temperature (36% at 723 K). Acetyl derivatives of (F) and (T) have been reduced to the corresponding carbinols which at higher temperatures underwent dehydration to vinyl derivatives and were further reduced to ethyl derivatives. This revised version was published online in June 2006 with corrections to the Cover Date.     

Synthesis, reactions and biological activity of 2-substituted 3-cyano-4,6-dimethylpyridine derivatives

The reaction of 2-chloro-4,6-dimethylpyridine-3-carbonitrile with hydrazine hydrate, hydroxylamine, and anthranilic acid afforded the corresponding pyrazolo, isoxazolo, and pyridoquinazoline derivatives. Alkylation of 2-mercapto-4,6-dimethylpyridine-3-carbonitrile with ethyl chloroacetate or phenacyl bromide followed by cyclization in NaOH gave thienopyridine derivatives. Diazotization of ethyl 3-amino-4,6-dimethylthiеno[2,3-b]pyridine-2-carboxylate followed by the reaction with thiourea, guanidine carbonate, and hydroxylamine hydrochloride gave the corresponding thienopyridine derivatives. The biological activity of some new compounds has been discussed. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 43–51, Januar, 2009.     

A simple, two-step, site-specific preparation of fluorinated naphthalene and phenanthrene derivatives from fluorobromo-substituted alkenes

A facile two-step procedure for the site-specific preparation of fluorinated naphthalene and phenanthrene derivatives is described. The Sonogashira reaction of bromofluoro-substituted alkenes with terminal alkynes, followed by base-catalyzed cyclization in refluxing N-methyl-2-pyrrolidinone (NMP), affords the corresponding fluorinated naphthalene and phenanthrene derivatives in good yields.     

Application of Phase Transfer Catalysis in Heterocyclic Synthesis: Synthesis of Some New Polyfunctional Thiophenes,Thiopyrans, Pyridines and Oxazines

The reaction of compound 1 with CS 2 and different active halo compounds gave the corresponding thiophene derivatives 2a,b-4a,b , whereas treatment of compound 1 with CS 2 and active methylene compounds afforded the corresponding thiopyran derivatives 5a,b , 6a,b , 7 , and 8 . Also, 1,3-thioxane derivatives 9 and 10 were obtained by reacting compound 1 with CS 2 and different cycloalkanones. Thiophene and pyrrolidene derivatives 11 , 12a,b , and 13a,b were obtained by reacting compound 1 with phenyl isothiocyanate and different halo compounds. The active methylene compounds and/or cycloalkanones were treated with compound 1 in the presence of phenyl isothiocyanate to give pyridines, thiopyran and oxazine derivatives 14a,b-16a,b , 17a-19a , and 19b , respectively.     

Highly satisfactory alkynylation of alkenyl halides via Pd-catalyzed cross-coupling with alkynylzincs and its critical comparison with the sonogashira alkynylation

[reaction: see text] The Pd-catalyzed alkynylation of various alkenyl halides and triflates with alkynylzincs proceeds well even with alkynyl derivatives containing electron-withdrawing groups. The reaction appears to be highly general. Noteworthy is that the corresponding Sonogashira reactions under various reported conditions are significantly less satisfactory in all cases performed in this study.     

Polarized ethylenes. IV. Synthesis of polarized ethylenes using thioamides and methyl dithiocarboxylates and their application to syntheses of pyrazoles,pyrimidines, pyrazolo[3,4-d]pyrimidines,and 5-aza[2.2.3]cyclazines

Polarized ethylenes having both electron-donating (an amino or a methylthio group) and electron-accepting (cyano, carbamoyl, methyl ester) groups on the adjacent two olefinic carbon atoms were prepared by the condensation of S-alkylthioamidinium salts or methyl dithiocarboxylates with the corresponding active methylene compounds in good yields. These polarized ethylenes were alternatively synthesized by the reaction of thioamides or methyl dithiocarboxylates with tetracyanoethylene oxide in good yields. Reactions of these polarized ethylenes with hydrazine or guanidine derivatives occurred smoothly to give the corresponding pyrazole and pyrimidine derivatives in good yields. The synthesis of 5-aza[2.2.3]cyclazine derivatives using polarized ethylenes is also described.     

Synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines; key synthons in syntheses of pharmaceutically active compounds

Substituted 10,11-dihydro-5H-dibenz[b,f]azepines are key synthons in the syntheses of a number of pharmaceutically active compounds such as imipramine, chlorimipramine, and desimipramine analogues. A facile synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines is described, starting out from com mercially available 2-bromotoluenes or 2-nitrotoluenes. Initial α-bromination with N-bromosuccinimide and subsequent reaction with triethylphosphite afforded the corresponding benzyl phosphonic ester deriva tives. After reaction with benzaldehyde derivatives, the expected Horner-Emmons reaction products were obtained. Hydrogenation gave the amino derivatives which were transformed into the corresponding formamides. Under Goldberg conditions [1], the final ring closing step was performed to give the substituted 10,11-dihydro-5H-dibenz[b,f]azepines in 46–75% yield.     

Palladium-catalyzed asymmetric amination and imidation of 2,3-allenyl phosphates

[reaction: see text] Asymmetric amination of 2,3-allenyl phosphates with nitrogen nucleophiles such as amines, hydroxylamines, and imides can be performed efficiently using a combination of zerovalent palladium complexes and SEGPHOS or MeOBIPHEP ligand, affording the corresponding optically active 1-aminated derivatives with enantiomeric excess of up to 97% ee.     

Chiral hetero Diels-Alder products by enantioselective and diastereoselective zirconium catalysis. Scope,limitation, mechanism,and application to the concise synthesis of (+)-Prelactone C and (+)-9-deoxygoniopypyrone

Catalytic asymmetric hetero Diels-Alder (HDA) reactions using a chiral zirconium complex have been developed. The reactions of aldehydes with Danishefsky's dienes proceeded smoothly to afford the corresponding pyranone derivatives in high yields with high diastereo- and enantioselectivities in the presence of a chiral zirconium complex, which was prepared from zirconium tert-butoxide, (R)-3,3'-diiodobinaphthol or its derivative, a primary alcohol, and a small amount of water. It is noted that 2,3-trans-pyranone derivatives were obtained with remarkably high diastereo- and enantioselectivities in the reaction with 4-methyl Danishefsky's diene. This is the first example of catalytic asymmetric trans-selective hetero Diels-Alder reactions of aldehydes. Furthermore, asymmetric HDA reactions with 4-benzyloxy Danishefsky's dienes were conducted to afford 2,3-cis-pyranone derivatives in high selectivities. Isolation of an intermediate of this asymmetric hetero Diels-Alder reaction indicated that the reaction proceeded in a stepwise cycloaddition pathway. Finally, these catalytic, asymmetric hetero Diels-Alder reactions were successfully applied to concise syntheses of biologically important natural pyranone derivatives, (+)-Prelactone C and (+)-9-deoxygoniopypyrone.     

Synthesis of the side chain cross-linked tyrosine oligomers dityrosine, trityrosine, and pulcherosine

[reaction: see text] An efficient synthesis of dityrosine and the first syntheses of the tyrosine trimers trityrosine and pulcherosine have been achieved. Protected 3-iodotyrosine underwent tandem Miyaura borylation-Suzuki coupling to give protected dityrosine. The choice of benzyl carbamate, ester, and ether protecting groups enabled a one-step global deprotection to give dityrosine. Suzuki coupling of protected 3,5-diiodotyrosine and tyrosine-3-boronic acid derivatives gave the corresponding trityrosine, but in low yield. However, use of a potassium tyrosine-3-trifluoroborate derivative in place of the corresponding pinacol boronate ester, in combination with protecting group variation, gave protected trityrosine in good yield. Access to pulcherosine was achieved through copper-catalyzed coupling of phenylalanine-4-boronic acid and 4-O-protected dopa derivatives to give an isodityrosine derivative. Selective halogenation followed by Suzuki coupling with the potassium tyrosine-3-trifluoroborate gave protected pulcherosine. Global deprotection of the protected trityrosine and pulcherosine derivatives completed the first syntheses of the corresponding tris-alpha-amino acids.     

Facile synthesis of multi‐functional 1,3,4‐thiadiazine derivatives bearing phthalazine,pyridazine, and pyrido‐pyridazine moieties

A series of novel, multifunctional 1,3,4‐thiadiazine derivatives bearing phthalazines, pyridazines and pyrido‐pyridazines ( 9–13 ) have been synthesized via the multicomponent reaction of (3‐(2‐bromo‐2‐[2‐chloropyrimidin‐4‐yl]acetyl)‐2‐chlorophenyl)‐2,6‐dichloro benzene‐sulfonamide with thiocarbohydrazide and various anhydrides. The reactions were performed by refluxing the components in mixed ethanol/acetic acid to afford the corresponding products in good to excellent yields. All the synthesized compounds were characterized by analytical and spectral studies. The developed method features short reaction time, simple work‐up without chromatographic separation, and a broad range of substrate applicability.     

Reactions of derivatives of 4a,9-diaza-1,2,4a,9a-tetrahydro-6H-fluorene with nucleophilic reagents and bromine

The reaction of quinone mono- and diimines of the 4a,9-diaza-12,4a,9a-tetrahydro-6H-fluorene series with aniline and thiophenol gives the corresponding 7-monosubstituted derivatives; with o-phenylenediamine and o-aminophenol the corresponding 6,7-annellated products are formed. Methylenequinone imines of this series, and also the 7,8-benzannellated analogs ofdiazahydrofluorenes, do not react with these nucleophiles. The bromination of diazahydrofluorene derivatives involves both the quinoid system and the enamine fragment.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 982–989, July, 1991.     

First reactions of dialkoxycarbenium tetrafluoroborates with pyrroles, 5H-dibenz[b,f]azepines,and electron-rich arenes

Pyrrole ( 2a ) and 2,5-dimethylpyrrole ( 2b ) react with the dialkoxycarbenium tetrafluoroborates 1a-1c under kinetic control to yield the corresponding acylpyrrole derivatives. 5H-Dibenz[b,f]azepine ( 9a ) and the 10,11-dihydro derivative 9b react only with the most electrophilic of the series of electrophiles tested, namely, diethoxycarbenium tetrafluoroborate ( 1a ), to furnish the corresponding formyl derivatives. Similarly, in arene chemistry, the highly electron-rich N,N-dimethylaniline ( 13a ) and 1,3,5-trimethoxybenzene ( 13b ) are formylated by reaction with 1a .