Synthesis and Synthetic Application of Phosphonoketene Dithioacetals. New Synthesis of Dithioallenes and (alpha-Dithiocarboxyvinyl)phosphonates

Phosphonoketene dithioacetals 3a-e were obtained in good yields by the reaction of ethyl phosphonoacetates 1a,b with 2-4 equiv of thiols 2a-c in the presence of an alkylaluminum dichloride or dialkylaluminum chlorides. Reaction of 2,2-dithio-1-phosphonovinyl anions with aldehydes afforded allylic alcohols 4-7, 11-18 in good to moderate yields. Treatment of the alcohols 4-6 with t-BuOK in THF led to symmetrical [2 + 2] cycloadducts 20-22 of 1,1-(ethylenedithio)allenes in moderate yields, while a similar reaction of the alcohols 11-13 produced a mixture of symmetrical and unsymmetrical [2 + 2] cycloadducts of 1,1-(trimethylenedithio)allenes,23a-25a and 23b-25b, in 55-94% yields. The alcohol 15 on a similar treatment gave 3-tert-butyl-1,1-bis(ethylthio)allene (26) in quantitative yield. The structures of 20 and 23b were determined by X-ray analysis. Treatment of the alcohols 15 and 18 with trifluoromethanesulfonic acid/n-Bu(4)NX (X = Br, I) or triphenylphosphine/CBr(4) in CH(2)Cl(2) afforded alpha-phosphonodithioacryclic acid esters 34 and 35 in 25-52% yields. The tandem Michael-Wittig reaction of 35 with sodium salt of 2-pyrrolecarbaldehyde in DMF gave ethyl 3-phenyl-3H-cyclopenta[a]pyrrole-2-dithiocarboxylate (36) in 25% yield.     

Synthesis and antimicrobial activity of aminomethoxy-substituted 1-(ethylthio)heptanes

The Mannich condensation of 1-(ethylthio)heptane-2-ol, formaldehyde and secondary amines taken in equimolar amounts gives rise to new aminomethoxy-substituted 1-(ethylthio)heptanes in a yield of 70–77%. The structure of the synthesized compounds was proved by the elemental analysis, IR and ¹H NMR spectroscopy, and mass spectrometry. The compounds were tested as antimicrobial additives to lubricating oils. They were found to suppress effectively the activity of microorganisms.     

Lewis acid-promoted deoxygenative di[beta,beta-bis(ethylthio)]vinylation of aldehydes with trimethylsilylketene bis(ethylthio)acetal

Silylketene dithioacetal 1 reacted with aldehydes 2a-o, 14, or cinnamaldehyde (11) in the presence of Lewis acid to give deoxygenative divinylation products, 3-substituted 1,4-pentadienes 3a-o, 15, or 5-phenyl-1,3,6-heptatriene 13b, in good to moderate yields. Similar reaction with 2-aminobenzaldehyde (16) or salicylaldehyde (17) produced quinoline 19 or chroman 20 in 40-58% yield. Treatment of 1 with alpha-diketones 22a-c or alpha-ketoester 24 led to tetrasubstituted furans 23a-c or allylic alcohol 25, respectively, in rather low yields. The formation mechanisms of these products are discussed.     

二硝酸根二4′，5′-二氮-9′-(4，5-二(硫乙基)-1，3-二硫杂环戊烯-2-叶立德)-芴合镉的合成、结构及光谱性质

Cd(NO₃)₂·4H₂O与配体4′,5′-二氮-9′-(4，5-二(硫乙基)-1，3-二硫杂环戊烯-2-叶立德)-芴(L)在甲醇和二氯甲烷的混合溶剂中生成配合物Cd(NO₃)₂(L)₂。晶体的空间群是Pbcn(#60)，晶体学参数分别是a=1.578 7(2) nm，b=0.987 96(11) nm，c=2.719 5(3) nm。V=4.241 6(8) nm³，Z=4。2个硝酸根离子各提供1个氧原子，2个配体L各提供2个氮原子，形成了镉的6配位结构。晶体结构显示分子通过平面之间的π-π相互作用沿b轴形成柱状结构，这些柱通过中心原子镉(Ⅱ)的配位连接形成二维层状结构，再通过2个硫乙基上的短距离S…S接触进一步形成了三维结构。对其 ¹H NMR、UV-Vis和荧光光谱进行了研究。     

Reduktive Co-Alkylierung von Heptamethyl-cobyrinat mit dem Methylthiomalonat (S)-Methyl-3-bromo-2-[(ethylthio) carbonyl]-2-methylpropanoat

Reductive Co Alkylation of Heptamethyl Cobyrinate with the Methylthiomalonate (S)-Methyl 3-Bromo-2-[(ethylthio)carbonyl]-2-methylpropanoate The methylthiomalonate(?)-(S)-Methyl 3-bromo-2-[(ethylthio)carbonyl]-2-methylpropanoate( 5a )was prepared from dimethyl methylmalonate in five steps via the stereospecific cleavage of the (pro-S)-ester group of 1 with pig-liver esterase in an overall yield of 26.5% (Scheme 4a). Reductive Co alkylation of heptamethyl Coβ-perchlorato cob (II)yrinate ( 8 ) with 5a by electrosynthesis lead to the alkylcobalt complex 9a in 40% yield (Scheme 4b). The O2-dependent reactions of the methyhnalonyl fragment produced by photolysis of 9a and its deuterated derivative 9c are reported (Scheme 5).     

Ring-closure reactions of 1,2-diaza-4,5-benzoheptatrienyl metal compounds: experiment and theory

2-Alkenylbenzylidene hydrazones 5a-m, which are accessible in good to excellent yields in a four-step synthesis, are converted into 1,2-diaza-4,5-benzoheptatrienyl metal compounds 1a-m by treatment with KO-t-Bu as base. These metal compounds undergo the various types of reactions in good yields and exclusively depending on the nature of substituents R(1) and R(3). Thus, metal compounds 1a-c carrying alkyl substituents R(1) and R(3) form 3H-benzodiazepines 6a-c after electrophilic quench of the intermediate cyclic anion 7 in a 7-endo-trig electrocyclic reaction with a mo?bius aromatic transition structure 1(-)-TS. Similarly, a benzothienyl derivative 5n is converted into diazepine 6d. Potassium compounds 1d-h, which are N-methyl and aryl substituted at R(3), form 1,2-dihydrophthalazines 8a-e in a predominantly charge-controlled 6-exo-trig cyclization reaction. In contrast, aryl-aryl-substituted systems 5i-m did not lead to cyclic products upon deprotonation, but the intermediate open-chain metal compounds 1i-m were trapped by acid chlorides at N1 to yield the hydrazides 10a-e. We interpret thermodynamics and kinetics of these reactions in the context of the Baldwin rules on the basis of quantum chemical calculations and discuss the transition structures considering the results of NICS and NBO-charge calculations. Examples of the products 6, 8, and 10 could be characterized by X-ray diffraction.     

Nuclear hydroxylated metabolite of fluradoline (2-fluoro-11-[(β-methylamino)ethylthio]dibenz[b,f]oxepin hydrochloride). Identification and synthesis

Fluradoline (2-fluoro-11-[β-(methylamino)ethylthio]dibenz[b,f]oxepin), a novel analgesic with an unique profile, was found to be extensively metabolized in man as well as in other species. One of the major metabolites of this drug appeared to be a nuclear hydroxylated derivative of the parent compound, and the site of enzymatic hydroxylation was established to be C(7) by using high-field proton nuclear magnetic spectroscopy. This structural assignment was subsequently confirmed by the synthesis of an authentic sample of 2-fluoro-7-hydroxy-11-[β-(methylamino)ethylthio]dibenz[b,f]oxepin ( 2a ).     

Hydrozirconation of stannylacetylenes. Synthesis and reactions of ketene Stannyl(Telluro) acetals

Stannylacetylenes 7a-e react with Cp(2)Zr(H)Cl in THF at room temperature to give the alpha-zirconated vinylstannane intermediates 8a-e, which subsequently react with butyltellurenyl bromide (2.0 equiv) to give exclusively ketene stannyl(telluro) acetals 6a-e of E configuration. Similar reactions were performed using phenylselenenyl bromide (2.0 equiv) as the electrophile, but a mixture of products was formed including the expected ketene stannyl(seleno) acetals 12. Otherwise, the use of 1.4 equiv of Cp(2)Zr(H)Cl and 1.0 equiv of PhSeBr results in the exclusive formation of 12, in good yields. Treatment of ketene stannyl(telluro) acetals with iodine or NBS followed by reductive dehalogenation results in the formation of 1-iodo-1-telluroalkenes 4a-e and 1-bromo-1-telluroalkenes 5a-e, respectively, with total retention of the configuration.     

Asymmetric PTC C-alkylation catalyzed by chiral derivatives of tartaric acid and aminophenols. Synthesis Of (R)- and (S)-alpha-methyl amino acids

A new type of efficient chiral catalyst has been elaborated for asymmetric C-alkylation of CH acids under PTC conditions. Sodium alkoxides formed from chiral derivatives of tartaric acid and aminophenols (TADDOL's 2a-e and NOBIN's 3a-h) can be used as chiral catalysts in the enantioselective alkylation, as exemplified by the reaction of Schiff's bases 1a-e derived from alanine esters and benzaldehydes with active alkyl halides. Acid-catalyzed hydrolysis of the products formed in the reaction afforded (R)-alpha-methylphenylalanine, (R)-alpha-naphthylmethylalanine, and (R)-alpha-allylalanine in 61-93% yields and with ee 69-93%. The procedure could be successfully scaled up to 6 g of substrate 1b. When (S,S)-TADDOL or (R)-NOBIN are used, the (S)-amino acids are formed. A mechanism rationalizing the observed features of the reaction has been suggested.     

Neutral and cationic chiral NCN pincer nickel(II) complexes with 1,3-bis(2'-imidazolinyl)benzenes: synthesis and characterization

Chiral 1,3-bis(2'-imidazolinyl)benzenes 1a-e easily undergo direct nickelation at the C2 position of the central benzene ring via the C-H bond activation in the reaction with anhydrous NiCl(2) giving neutral NCN pincer nickel(II) complexes 2a-e in 40-87% yields. Treatment of the nickel pincers 2a or 2c with AgBF(4) in CH(3)CN-CH(2)Cl(2) afforded the cationic nickel pincers 3a or 3c in good yields. All the complexes were characterized by elemental analysis, (1)H, (13)C NMR, and IR spectra. Molecular structures of the neutral complexes 2a, 2b and 2c as well as the cationic complex 3c have been determined by X-ray single-crystal diffraction. The cationic nickel pincers 3 are found to be effective catalysts for the Michael addition of ethyl 2-cyanopropionate to methyl vinyl ketone in the presence of i-Pr(2)NEt base with a catalyst loading of 5 mol% even at -78 °C, producing the adduct in >99% yield after 24 h albeit with no ee.     

Synthesis and Crystal Structure of Pd(AETYF)Cl_2CH_2Cl_2 [AETYF = 4''''5''''Diaza-9'''' (4,5-bis(ethylthio)-1,3-dithiole-2-ylidene)-fluorene]

1 INTRODUCTION Over the past decades, extensive work has been carried out to study palladium complexes in organic synthesis, structural analysis, chemical reactivity, catalytic process, spectroscopy and functional mate- rials[1]. Especially the anti…     

Photocyclization reactions. Part 4 . Synthesis of naphtho[1,8-bc]-furans and cyclohepta[cd]benzofurans using photocyclization of Ethyl 2-(8-Oxo-5,6,7,8-tetrahydro-1-naphthyloxy)acetates and ethyl 2-(5-Oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-4-yloxy)acetates

Photocyclization reactions were carried out on ethyl 2-(8-oxo-5,6,7,8-tetrahydro-1-naphthyloxy)acetates 1a-e and ethyl 2-(5-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-4-yloxy)acetates 2a-e in acetonitrile. Irradiation of 1a-e gave naphtho[1,8-bc]furanols 3a-e and naphtho[1,8-bc]furans 4a-e in 33–83% yields and ethyl acrylates 5b-d were produced in 3–25% yields during irradiation of 1b-d . On the other hand, 2a-e afforded cyclohepta[ad|benzofuranols 6a-e and cyclohepta[ad]benzofurans 7a-e in 44–87% yields. Ethyl acrylates 8b-d were also produced in 7–43% yields from irradiation of 2b-d . Substituent effects on photocyclization and reaction pathways are discussed.     

(Alpha-aminoacyl)amino-substituted heterocycles and related compounds

N-Protected-(aminoacyl)benzotriazoles 1a-e, g, i, j, 1a'-c' convert heterocyclic amines of the following series: thiazoles (3a and 3a'), benzothiazoles (3b and 3b'), benzimidazoles (3c and 3c'), thiadiazoles (3d), pyrimidones (9a, b, a'), pyrazoles (11a, b), and pyridines (13a-g, 13d') under microwave irradiation, into N-substituted amides in yields of 40-98% (average 76%). N-Protected peptidoylbenzotriazoles 6a, b similarly afforded C-terminal N-protected dipeptidoyl amides 7a, b (52-60%).     

A new route to the improved synthesis of 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils

A new route to C-6-selenenyl analogs of compound 1a from 5-alkyl-6-chlorouracils 6a-b has been described. A mild and highly efficient synthesis of 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils 8a-e has been accomplished from 6a-b in good yields using a two step procedure. Silylation of 5-alkyl-6-chlorouracils 6a-b using N,O-bis(trimethylsilyl)acetamide followed by regioselective alkylation of the silylated intermediate with ethyl or benzyl chloromethyl ether in dichloromethane afforded the desired 1-(alkoxymethyl)-5-alkyl-6-chlorouracils 7a-d in 88–94% yields. Compounds 7a-d readily underwent addition-elimination reaction with an appropriate arylselenol in the presence of ethanolic sodium hyroxide to produce the corresponding 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils 8a-e in excellent yields (94–99%).     

First examples of oxaphosphirane pentacarbonylchromium(0) and -molybdenum(0) complexes: synthesis, structures and reactions

Synthesis of the first oxaphosphirane chromium(0) and molybdenum(0) complexes of the type [{(R(1)PCH(R(2))-O}M(CO)(5)] (R(1) = C(5)Me(5)) (8a-e, 15a-e) and (R(1) = CH(SiMe(3))(2)) (9a-e, 16a-e) via reaction of dichloro(organo)- (1, 2, 10, 11) and chloro(organo)phosphane complexes (3,4,12) with lithium bases and aldehydes 7a-e is reported. Furthermore, bicyclic 1,3-oxaphospholane complexes 17 and 18 have been obtained via O-protonation of oxaphosphirane complexes 8a and 15a with HCl. All complexes were characterized by NMR, IR spectroscopic, mass spectrometric investigations and, in addition, single-crystal X-ray structures of complexes 8a-e, 9a,c, 15a,b,e, 16a-c, 17, 18 are presented and discussed.     

Synthesis and structure of a series of new d(1)-Aryl imido-vanadium(IV) complexes stabilized by n-donor ligands

A family of new coordination vanadium(IV) compounds supported by a terminal or bridged aryl imido ligand are reported. Reaction of V(NMe(2))(4) with anilines ArNH(2), where Ar = 2,6-i-Pr(2)-C(6)H(3), 2,6-Me(2)-C(6)H(3), Ph, 2,6-Cl(2)-C(6)H(3), and C(6)F(5), afforded the diamagnetic imido-bridged complexes [V(NAr)(NMe(2))(2)](2) (1a-e). Chlorination of 1a-e with trimethylchlorosilane afforded complexes 2a-e formulated as [V(=NAr)Cl(2)(NHMe(2))(x)()](n)(). One-pot reaction of V(NMe(2))(4) with ArNH(2) in the presence of an excess of trimethylchlorosilane gave the five-coordinate compound [V(=NAr)Cl(2)(NHMe(2))(2)] (3a-e). Reaction of 3a-e with pyridine, bipyridine (bipy), or N,N,N',N'-tetramethylethylenediamine (tmeda) gave respectively the six-coordinate tris- or bis(pyridine) adducts [V(=NAr)Cl(2)(Py)(3)] (4a-e) or [V(=NAr)Cl(2)(Py)(2)(NHMe(2))] (5a), bipyridine complexes [V(=NAr)Cl(2)(bipy)(NHMe(2))] (5a-e) and [V(=NAr)Cl(2)(bipy)(Py)] (9a), and tmeda adduct [V(=NAr)Cl(2)(tmeda)(NHMe(2))] (10a). Moreover, five-coordinate complexes free of NHMe(2) ligands, such as [V(=NAr)Cl(2)(Py)(2)] (5a), [V(=NAr)Cl(2)(bipy)] (8a), and [V(=NAr)Cl(2)(tmeda)] (11a), were directly prepared starting from precursors 2a-e. All compounds were totally characterized by spectroscopic methods (IR, (1)H NMR for diamagnetic complexes, and EPR for paramagnetic complexes), elemental analysis, magnetism, and single-crystal X-ray diffraction studies for 1b, 3a, 3d, 4b, 4d, 7c, 10a, and 11a.     

Asymmetric synthesis of anti-homopropargylic alcohols from aldehydes and chiral sulfonimidoyl substituted bis(allyl)titanium complexes through generation and elimination of novel chiral alkylidenecarbene (dimethylamino)sulfoxonium ylides

A new method for the asymmetric synthesis of anti-configured homopropargylic alcohols 1 is described, which features the addition of chiral sulfonimidoyl substituted bis(allyl)titanium complexes 3 to aldehydes, the methylation of sulfonimidoyl substituted homoallylic alcohols 2 at the N-atom, and the elimination of alkenyl (dimethylamino)sulfoxonium salts 7 with LiN(H)tBu. The reaction of isopropyl, cyclohexyl, and methyl substituted allylic titanium complexes 3a-c with benzaldehyde, p-bromobenzaldehyde, p-chlorobenzaldehyde, p-methoxybenzaldehyde, (E)-3-phenylpropenal, and phenylpropynal afforded with high regio- and diastereoselectivities the anti-configured sulfonimidoyl substituted homoallylic alcohols 2a-j, respectively. Only one allylic unit of the titanium complexes 3a-c was transferred in the case of unsaturated aldehydes, and the starting allylic sulfoximines 2a-g were recovered in approximately 50% yield. The methylation of the silyl protected alkenyl sulfoximines 6a-j with Me(3)OBF(4) gave in practically quantitative yields the (dimethylamino)sulfoxonium salts 7a-j, respectively. Salts 7a-e, 7g, 7h, and 7j delivered upon treatment with 2 equiv of LiN(H)tBu the enantio- and diastereomerically pure saturated and unsaturated alkynes 9a-e, 9g, 9h, and 9j, respectively, in high yields. Besides the alkynes the sulfinamide 8 (96% ee) was isolated. Aminosulfoxonium salts 9f and 9i, which carry a CC triple bond, also suffered an elimination under these conditions but did not yield the corresponding diynes. Elimination of salts 7a-e, 7g, 7h, and 7j proceeds most likely through deprotonation at the alpha-position with formation of the novel alkylidenecarbene aminosulfoxonium ylides 19a-e, 19g, 19h, and 19j, respectively. The ylides 19a-e, 19g, 19h, and 19j presumably eliminate sulfinamide 8 with generation of the chiral nonracemic (beta-siloxyalkylidene)carbenes 20a-e, 20g, 20h, and 20j, which suffer a 1,2-H-shift with formation of alkynes 9. Support for the formation of the putative alkylidenecarbenes 20 as intermediates comes from the elimination of the beta-methyl substituted aminosulfoxonium salt 24, which delivered the enantio- and diastereomerically pure 2,3-dihydrofuran derivative 28 upon treatment with LiN(H)tBu in high yield. Here, the putative (beta-siloxyalkylidene)carbene 26 suffers a 1,5-O,Si bond insertion rather than a 1,2-Me shift. Methylation of the alkenyl sulfoximine 6a at the alpha-position with formation of 13 was achieved through deprotonation of the former with formation of the alpha-lithioalkenyl sulfoximine 11a and its treatment MeI. Reaction of the alpha-methylated alkenyl aminosulfoxonium salt 14a with LiNiPr(2) at low temperatures gave the enantio- and diastereomerically pure anti-configured homoallenylic alcohol derivative 15, while reaction of the salt with LiNiPr(2) or LiN(H)tBu at higher temperatures afforded the enantio- and diastereomerically pure nonterminal homopropargylic alcohol derivative 17. Deprotonation of the alkenyl (dimethylamino)sulfoxonium salts 7a and 7b with nBuLi afforded the novel alkylidenecarbene aminosulfoxonium ylides 19a and 19b, respectively, which upon treatment with MeI yielded the methylated aminosulfoxonium salts 14a and 14b, respectively.     

Asymmetric aza-Mannich addition: synthesis of modified chiral 2-(ethylthio)-thiazolone derivatives with anticancer potency

An easily prepared cinchona alkaloid derivative was found to be an effective organocatalyst in a direct, enantioselective aza-Mannich addition. By establishing a quaternary carbon stereocenter, a series of modified chiral 2-(ethylthio)-thiazolone derivatives have been obtained with excellent diastereo- and enantioselectivities. And these derivatives have been found to show anticancer activities against five different cancer cell lines using the MTT assay.     

Syntheses of pyrrolo- and indoloisoquinolinones by intramolecular cyclizations of 1-(2-arylethyl)-5-benzotriazolylpyrrolidin-2-ones and 3-benzotriazolyl-2-(2-arylethyl)-1-isoindolinones.

1,5,6,10b-Tetrahydropyrrolo[2,1-alpha]isoquinolin-3(2H)-ones 17a,b, 17d,e, and 5,12b-dihydroisoindolo[1,2-alpha]isoquinolin-8(6H)-ones 22a-e were prepared by intramolecular cyclizations of 1-(2-arylethyl)-5-benzotriazolyl-pyrrolidin-2-ones 15a,b, 15d,e, and 3-benzotriazolyl-2-(2-arylethyl)-1-isoindolinones 20a-e, respectively, in the presence of titanium chloride. Products from chiral amines were obtained with stereoselectivities of > or = 94%.     

Acylphosphonamidates and α-hydroxyiminophosphonamidates. Synthesis of N-acylphosphordiamidates by Beckmann rearrangement. Crystal structure of (E)-α-hydroxyiminobenzyl-1-pyrrolidinylphosphinate

Reaction of methyl benzoylphosphonochloridate (3) with a secondary or primary series of amines yielded methyl benzoylphosphonamidates, 4a-e. The latter compounds reacted with hydroxylamine to yield a-hydroxyiminobenzylphosphonamidates (5a-e), largely as (E)-isomers. The structure of methyl (E)-a-hydroxyimino-benzyl-1-pyrrolidinylphosphinate (5b) was determined by single-crystal X-ray crystallography. Heating oximes 5a-e in boiling toluene caused them to undergo Beckmann rearrangement to N-benzoylphosphordiamidates 6a-e. © 1996 John Wiley & Sons, Inc.