Synthesis of thiazolines linked to a difluoromethylphosphonate diester via dithioester chemistry

[reaction: see text] A two-step, high-yielding synthesis of delta(2)-thiazolines containing a difluoromethylphosphonate diester moiety has been devised using a building block approach. Racemic or chiral beta-amino alcohols and diols were coupled with methyl difluoro(diethoxyphosphono)dithioacetate to give predominantly the corresponding beta-hydroxythioamides, which were then cyclized to provide a series of novel substituted delta(2)-thiazolines.     

A simple and efficient L-prolinamide-catalyzed alpha-selenenylation reaction of aldehydes

An efficient and simple l-prolinamide-catalyzed alpha-selenenylation reaction of aldehydes with N-(phenylseleno)phthalimide has been developed for the efficient preparation of alpha-phenylselenoaldehydes. Such compounds are versatile building blocks for the synthesis of alpha,beta-unsaturated aldehydes, allylic alcohols, and amines. [reaction: see text]     

Fluoride ion-mediated nucleophilic fluoroalkylation of alkyl halides with Me3SiCF2SPh: Synthesis of PhSCF2- and CF2H-containing compounds

A facile and highly efficient nucleophilic (phenylthio)difluoromethylation of alkyl halides has been achieved via fluoride ion-mediated substitution reaction using [difluoro(phenylthio)methyl]trimethylsilane (Me₃SiCF₂SPh). The reaction proceeds well with primary alkyl bromides (or alkyl iodides) in DME solvent when CsF/15-crown-5 was used as the fluoride source/additive. The PhSCF₂-containing products can be readily transformed into CF₂H-containing compounds via a free-radical desulfurization method.     

The synthesis of difluoro[1]benzothieno[2,3-c]quinolines and their N-methyl quaternary salts

A series of difluoro[1]benzothieno[2,3-c]quinolines has been prepared by photocyclization of the appropriate carboxamides. The lactams obtained were converted into the corresponding chloro derivatives which were catalytically dechlorinated into the difluoro[1] benzothieno[2,3-c]quinolines. The latter compounds were transformed into the N-methyl quaternary salts.     

Simple, facile, and one-pot conversion of the Baylis-Hillman adducts into functionalized 1,2,3,4-tetrahydroacridines and cyclopenta[b]quinolines

A simple, facile, and one-pot synthesis of functionalized 1,2,3,4-tetrahydroacridines and cyclopenta[b]quinolines from the Baylis-Hillman alcohols, i.e., 2-[hydroxy(2-nitroaryl)methyl]cycloalk-2-enones, is described.     

Novel selectfluor and deoxo-fluor-mediated rearrangements. New 5(6)-methyl and phenyl methanopyrrolidine alcohols and fluorides

Stereoselective syntheses of novel 5,6-difunctionalized-2-azabicyclo[2.1.1]hexanes containing 5-anti-fluoro or hydroxyl in one methano bridge and a variety of syn- or anti-chloro, fluoro, hydroxy, methyl, or phenyl substituents in the other methano bridge have been effected. Rearrangements of iodides to alcohols were initiated using Selectfluor. Rearrangement of alcohols to fluorides was initiated using Deoxo-Fluor. Ring opening of 2-azabicyclo[2.2.0]hex-5-ene exo-epoxide with organocopper reagents is regioselective at C(5).     

Direct, facile aldehyde and ketone alpha-selenenylation reactions promoted by L-prolinamide and pyrrolidine sulfonamide organocatalysts

[reaction: see text] A new catalytic method for direct alpha-selenenylation reactions of aldehydes and ketones has been developed. The results of exploratory studies have demonstrated that L-prolinamide is an effective catalyst for alpha-selenenylation reactions of aldehydes, whereas pyrrolidine trifluoromethanesulfonamide efficiently promotes reactions of ketones. Under optimized reaction conditions, using N-(phenylseleno)phthalimide as the selenenylation reagent in CH2Cl2 in the presence of L-prolinamide (2 mol %) or pyrrolidine trifluoromethanesulfonamide (10 mol %), a variety of aldehydes and ketones undergo this process to generate alpha-selenenylation products in high yields. Mechanistic insight into the L-proline and L-prolinamide catalyzed alpha-selenenylation reactions of aldehydes with N-(phenylseleno)phthalimide has come from theoretical studies employing ab initio methods and density functional theory. The results reveal that (1) the rate-limiting step of the process involves attack of the enamine intermediate at selenium in N-(phenylseleno)phthalimide and (2) the energy of the transition state for the reaction catalyzed by prolinamide is lower than that promoted by proline. This result is consistent with experimental observations. The role of hydrogen bond interactions in stabilizing the transition states for this process is also discussed.     

Preparation of alpha-(2,2-diphenylhydrazino)lactones and related compounds by radical cyclization: use of glyoxylic acid hydrazone derivatives

Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b) are easily esterified in high yield by beta-bromo alcohols. The resulting esters undergo radical cyclization to alpha-(2,2-diphenylhydrazino)- or alpha-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for radical cyclization were also made using a beta-(phenylseleno) alcohol and an enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of the nitrogen substituent (28 --> 30) so that an alpha-amino lactone can be generated by acid hydrolysis of the cyclization product.     

Difluoro-lambda3-bromane-induced oxidative carbon-carbon bond-forming reactions: ethanol as an electrophilic partner and alkynes as nucleophiles

Reported here for the first time are the oxidative couplings of alkynes and primary alcohols yielding conjugated enones. Although the BF3-catalyzed reaction of terminal alkynes with p-trifluoromethylphenyl(difluoro)-lambda3-bromane results in the fluoro-lambda3-bromanation of triple bonds to afford (E)-beta-fluorovinyl-lambda3-bromanes, reaction of an alkyne with the difluoro-lambda3-bromane in the presence of an alcohol and BF3-Et2O affords directly conjugated enones in good yields. The reaction proceeds in a highly stereo- and regioselective manner under metal-free conditions. Interestingly, no formation of enones was detected, when difluoro-lambda3-iodane p-CF3C6H4IF2 was used instead of the lambda3-bromane. A mechanism involving a lambda3-bromane-induced oxidation of an alcohol to an aldehyde, [2 + 2] cyclization with alkynes yielding 2H-oxetes, and finally the electrocyclic ring opening is discussed.     

Solvent‐free Synthesis of 2,6‐Dihydroxy‐9H‐purin and Pteridine Derivatives

5,6‐Diaminopyrimidin‐2,4‐diol 1 was reacted with 1,4‐d ‐gluconolactone 2 , 6‐chloro‐4‐cyclopropyl‐7‐floro‐1,4‐dihydro‐1‐oxonaphthalen‐2‐carboxilic acid 4 , (3S)‐9,10‐difloro‐3,7‐dihydro‐3‐methyl‐7‐oxo‐2H‐[1,4]oxazino[2,3,4‐ij]quinolin‐6‐carboxylic acid 6 , and dimethylacetylendicarboxylate to afford 1‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)‐sorbitol 3 , 7‐chloro‐1‐cyclopropyl‐6‐flouro‐3‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)quinoline‐4(1H)‐one 5 , 9,10‐difluoro‐2,3‐dihydro‐6‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)‐3‐methyl‐[1,4]oxazine[2,3,4‐ij]quinoline‐7‐one 7 , and (2,4‐dihydroxy‐6‐oxo‐5,8‐dihydro‐6H‐pteridine‐7‐yiliden)‐acetic acid methyl ester 9 , respectively. The synthesized compounds characterized by IR, ¹H‐NMR, ¹³C‐NMR, GC‐mass, and elemental analysis.     

Asymmetric [2 + 1] Cycloaddition Reactions of 1-Seleno-2-silylethene

The reaction of (E)-1-(phenylseleno)-2-(trimethylsilyl)ethene (1) and vinyl ketones 2a-d in the presence of a chiral Lewis acid prepared from TiCl(4), Ti(O(i)Pr)(4), (R)- or (S)-1,1'-binaphthol (BINOL), and MS4A gave enantiomerically enriched cis cyclopropane products 3a-d. The enantiomeric excess and chemical yield varied depending on the ratio of TiCl(4) and Ti(O(i)Pr)(4) to 1. Reproducible results (43-47% ee/33-41% yields) for cis-1-acetyl-2-[(phenylseleno)(trimethylsilyl)methyl]cyclopropane (3a) were obtained using 1.1 equiv of TiCl(4), 0.54-0.65 equiv of Ti(O(i)Pr)(4), and 1.65 equiv of BINOL. The observed enantioselectivity was explained by consideration of the structure of the postulated intermediates, alkoxy titanium-carbonyl complexes, via ab initio MO calculations.     

New process for the preparation of methyl carbonates

The methyl carbonate of HOBt was developed for the conversion of alcohols to carbonates. This method is superior to the use of methyl chloroformate or methyl pyrocarbonate, especially with more hindered alcohols. The reagent is a stable solid that is easily prepared on a multigram scale. [reaction: see text]     

Über quantitative Beziehungen Zwischen Fragmenten und Ihren Relativen Intensitäten im Massenspektrometer. III—Messung der Intensitätsverhältnisse aus der α-SWpaltung von Tertiären Alkjoholen und Äthern bei Niedriger Elektronenenergie

The ion intensity ratios from competing α-fissions of 30 tertiary aliphatic alcohols and 24 ethers of tertiary alcohols have been measured at 13 eV. The intensity ratios of ions [M ? alkyl1]+ and [M ? alkyl2]⁺ agree well with the reciprocal mass ratios of the respective ions in the case when the alkyl groups are not methyl (ion mass effect). The intensity ratios of [M ? alkyl]⁺ and [M ? methyl]⁺ are always too high, but intensity ratios of [M ? alkyl1]⁺ and [M ? alkyl2]⁺ may be derived indirectly from them, which also agree well with those values expected from the ion mass effect. By the indirect method it is shown, that for the 2,2-dialkyl-1,3-dioxolanes (ethylene ketals) the ion mass effect plays a dominant role too.     

General preparative route to benzo[g]quinolines (1-azaanthracenes)

A convenient synthetic pathway to benzo[g]quinolines (1-azaanthracenes) has been developed. The nickel catalyzed coupling of methyl 2-chloronicotinate ( 3a ) with benzylic organo zinc reagents 2a-e led to the methyl 2-benzylic substituted nicotinates 4a-e. Treatment of methyl 2-chloro-6-methylnicotinate ( 3b )with 2a in a similar manner led to methyl 2-benzyl-6-methyInicotinate ( 4f ). The coupling of 2-chloro-3-acetylpyridine ( 5 ) with benzyl zinc bromide ( 2a ) led to 2-benzyl-3-acetylpyridine ( 4g ). The coupling of the 2,5-dichlorobenzylic organic zinc reagent ( 2f ) with methyl 2-choronicotinate ( 3a ) was unselective but readily coupled with methyl 2-bromonicotinate ( 6 ) to yield methyl 2-(2,5-dichlorobenzyl)nicotinate ( 4h ). The esters 4a-f,h on reduction with lithium aluminum hydride led to the corresponding alcohols 7a-f,h which were subsequently oxidized with manganese dioxide to the respective 2-benzylic substituted pyridine-3-carboxaldehydes 8a-f,h. In one case the coupling of benzy] zinc bromide ( 2a ) with 2-chloropyridine-3-carboxaldehyde ( 9 ) led directly to 2-benzylpyridine-3-carboxaldehyde ( 8a ), but in poor yield. Cyclizations of the aldehydes 8a-d,f,h or the ketone 4g with polyphosphoric acid afforded the benzo[g]quinolines 10a-d,f-h in high yields. Aldehyde 8e was cyclized to 10e using a solution of sulfuric acid in methanol. Several of the benzo[g]quinolines 10c,d could be readly converted into the benzo[q]quinoline-5,10-diones 11c,d on treatment with ammonium ceric nitrate.     

Unusual formation of a novel pyrrolo[1′,2′:1,2]pyrido[3,4-b]indole

Reaction of 1-methyl-3,4-dihydro-β-carboline 1 with methyl glycidate 4 gave the novel tetracyclic conjugated γ-lactam, 2-methylpyrrolo[1′,2′:1,2]pyrido[3,4–6]indol-3-one 5 . The same compound 5 was obtained in higher yield when 1 was treated with methyl 2-methoxyacrylate 7 . Sodium borohydride treatment of 5 resulted in the cleavage of lactam to yield the unexpected alcohols 8 and 9 .     

Biocatalytic reduction of a racemic selenocyclohexanone by Brazilian basidiomycetes

An efficient synthesis of the chiral cyclic secondary alcohols, trans-2-(phenylseleno)cyclohexanol 1a and cis-2-(phenylseleno)cyclohexanol 1a, was obtained by enzymatic reduction of 2-(phenylseleno)cyclohexanone 1 using whole fungal cells. Five strains of white-rot basidiomycetes were examined; Irpex lacteus CCB 196, Pycnoporus sanguineus CCB 196, Trametes rigida CCB 285, Trametes versicolor CCB 202 and Trichaptum byssogenum CCB 203. Cells of T. rigida CCB 285 gave alcohols cis-(RS)-1a and trans-(SS)-1a in high enantiomeric excesses (ca. 99%).     

Claisen ortho ester rearrangement with trimethyl 3-(phenylseleno)orthopropionate: A synthon for the preparation of 2-substituted acrylates and α-methylene-γ-butyrolactones

Trimethyl 3-(phenylseleno)orthopropionate may be utilized as a synthon for the preparation of either 2-substituted acrylates or α-methylene-γ-butyrolactones via Claisen ortho ester rearrangement with allylic alcohols followed by oxidative-elimination of PhSeOH.     

Reactions of 6,7-dimethoxy- 3,4-dihydroisoquinoline with <Emphasis Type="Italic">o</Emphasis>-quinone methides

Products of heterocyclization, 9,10-dimethoxy-12,13-dihydro-7aH,15H-naphtho[1',2':5,6][1,3]oxazino-[2,3-a]isoquinolines, were isolated on condensing 6,7-dimethoxy-3,4-dihydroisoquinoline with 1-dimethylaminomethyl-2-naphthols. In the case of o-hydroxybenzyl alcohols products of a Michael aza reaction, 2-[(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl]phenols were obtained.     

The first total synthesis of (+/-)-scopadulin, an antiviral aphidicolane diterpene

[reaction: see text] The first total synthesis of (+/-)-scopadulin was accomplished by a stereoselective construction of a quaternary carbon at C-4, conversion of the hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols, and a highly chemo- and stereoselective methylation at C-16.     

SYNTHESIS OF ABA TYPE TRIBLOCK COPOLYMERS BY RADICAL POLYMERIZATION WITH 1,4-BIS(p-TERTBUTYLPHENYLSELENOMETHYL) BENZENE AS A PHOTOINIFERTER

1,4-Bis(p-tert-butylphenylselenomethyl)benzene was used as a bifunctional photoiniferter for the polymerization of methyl methacrylate (MMA). Both the polymer yields and the number average of molecular weights ([Mbar]_n) of polymers increased with the polymerization time and the [Mbar]_n linearly increased with polymer yield. The addition of MMA to the poly(MMA) with irradiation increased the [Mbar]_n of the polymer. Photoirradiation of telechelic polystyrene having phenylseleno groups at both ends as polymeric photoiniferter in the presence of MMA or p-chloromethylstyrene afforded effectively corresponding to the ABA type triblock copolymers. On the other hand, photopolymerization of p-methylstyrene with ABA type triblock copolymer of styrene and p-chloromethylstyrene as polymeric photoiniferter afforded to multiblock copolymer of styrene and p-substituted styrenes.