A C-C bond formation reaction at the α-carbon atom of α-oxo ketene dithioacetals via the Baylis-Hillman type reaction

The first example of TiCl₄-mediated Baylis-Hillman type reaction of α-acetyl cyclic ketene dithioacetals with arylaldehydes was described. This methodology adds a new entry to the C-C bond formation at the α-carbon atom of α-oxo ketene dithioacetals.     

Efficient and Practical Route to α‐Aminocarbonylketene and α‐Cyanoketene Dithioacetals

An efficient and practical route to α‐aminocarbonylketene dithioacetals 5 and α‐cyanoketene dithioacetals 6 was developed. With readily available α‐acetyl‐α‐aminocarbonyl ketene dithioacetals 4 as the starting materials, α‐aminocarbonylketene dithioacetals 5 were prepared in high yield via base‐catalyzed (sodium hydroxide) deacetylation. In the presence of POCl₃ and with DMF as the solvent, α‐cyanoketene dithioacetals 6 were obtained via dehydration of 5 in excellent yield.     

Reactions of pyridinium or isoquinolinium ketene dithioacetals with aromatic N-imines and S-imines

Reactions of ketene dithioacetals, 1-[1-substituted 2,2-bis(methylthio)ethenyl]pyridinium 1a-i or -isoquinolinium 2a,b iodides with aromatic N-imines, 1-aminopyridinium 3a-1,1 -aminoquinolinium ( 4 ), and 2-amino-isoquinolinium ( 5 ) mesitylene sulfonates gave the corresponding 2-methylthioimidazo[1,2-a]pyridines 9a-k , 2-methylthiopyrazolo[1,5-a]pyridines 11a-q , 2-methylthioimidazo[2,1-a]isoquinoline derivatives 10a,b and 2-methylthiopyrazolo[1,5-a]quinoline ( 12 ). The benzoyl compounds, 1-[1-benzoyl-2,2-bis(methylthio)ethenyl]-pyridinium iodides 1g,h,i reacted with N-imine 3a to give the 3-benzoyl-2-methylthioimidazo[1,2-a]pyridines 9h-k . The reaction of pyridinium ketene dithioacetals 1a,f,g (R¹ = COOE_t, COPh, and CN) with substituted pyridinium N-imines having an electron-withdrawing group on the pyridine ring afforded only the corresponding pyrazolo[1,5-a]pyridine derivatives 11j-r in good yields. Reactions of ketene dithioacetals with various S-imines are also described. Possible mechanisms for the formation of 9 and 11 are described.     

Palladium‐Catalyzed C?S Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

The insertion of an aryne into a C S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α‐carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2‐quinolinones in high yields under neutral reaction conditions by a C S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio‐substituted quinolinone products.     

Palladium‐Catalyzed CS Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

The insertion of an aryne into a C? S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α‐carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2‐quinolinones in high yields under neutral reaction conditions by a C? S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio‐substituted quinolinone products.     

IODODECARBOXYLATION OF α-CARBOXYLATE, α-CINNAMOYL KETENE CYCLIC DITHIOACETALS

ABSTRACT

The iododecarboxylation reaction of α-carboxylate, α-cinnamoyl ketene cyclic dithioacetals 2 was successfully performed with iodine as halogenation reagent and in water insensitive media. This reaction provides a mild and efficient method for the preparation of α-iodo, α-cinnamoyl ketene cyclic dithioacetals 3 which are important kinds of potential new intermediates to be valued.     

Facile Synthesis of Nicotinic Acid Derivatives with Unsymmetrical Substitution Patterns

Abstract

Two novel methods for synthesis of nicotinic acid derivatives with unsymmetrical substitution patterns were presented via ketene dithioacetals. The ketene N,S-acetals 2 reacted with β-ketoesters or β-cyanoesters to give 4-amino-5-cyano-2-alkyl-6-methylthio-nicotinic acid derivatives 3 or 2,4-diamino-5-cyano-6-methylthio-nicotinic acid ethyl ester 4. However, 6-amino-5-cyano-2-alkyl-4-methylthio-nicotinic acid esters 6 were obtained by the reaction of the ketene dithioacetals 1 and β-amino-crotonates.     

Unexpected hydrobromic acid-catalyzed C-C bond-forming reactions and facile synthesis of coumarins and benzofurans based on ketene dithioacetals

Hydrobromic acid was found to be a unique catalyst in C? C bond‐forming reactions with ketene dithioacetals. Distinctly different from other acids (including Lewis and Brønsted acids), the remarkable catalytic performance of hydrobromic acid in catalytic amounts was observed in the “acid”‐catalyzed reactions of readily available functionalized ketene dithioacetals 1 with various electrophiles. Under the catalysis of 0.1 equivalents of hydrobromic acid, the reaction of 1 with carbonyl compounds 2 a – l gave polyfunctionalized penta‐1,4‐dienes 3 or conjugated dienes 4 in good to excellent yields. The reaction tolerated a broad range of substituents on both the ketene dithioacetals 1 and the carbonyl compounds 2 . Application of this efficient C? C bond‐forming method generated coumarins 5 and benzofurans 7 under mild, metal‐free conditions by hydrobromic acid‐catalyzed reactions of 1 with salicylaldehydes 2 m – o and p‐quinones 6 a – d , respectively. A new reactive species, a sulfur‐stabilized carbonium ylide, formed depending on the nature of the counterion, and this was proposed as the key intermediate in the unique catalysis of hydrobromic acid.     

Low‐valent Titanium Induced Reductive Coupling of O‐Nitrophenylazide with Benzoyl Substituted Ketene Dithioacetals: a Novel Synthesis of 4‐Aryl‐2‐methylthio‐3Z7‐l,5‐benzodiazepines

Treated with the low‐valent titanium derived from TiCl₄/Sm system, o‐nitrophenylazide could produce the intermediate 2 in situ, which reacted with benzoyl substituted ketene dithioacetals to afford 4‐aryl‐2‐methylthio‐3H‐1,5‐benzodiazepines in good yields under mild and neutral conditions.     

Sythesis of methylthiomaleimides for the preparation of pyridazines and related comopounds

New functionalized maleimides (3‐methylthio‐2,5‐dioxo‐1H‐pyrroles) were obtained by the reaction of ketene dithioacetals with nitromethane or the reaction of nitro ketene dithioacetal with active methylene compounds in the presence of the appropriate base in dimethyl sulfoxide followed by treatment with methanol. These nakeunudes reacted with various nucleophilic reagents such as election‐rich aromatic and heteroaromatic compounds like dialkylanilines, aminophenols, indoles, indolizines, and cyalazines to give the corresponding 3‐aryl‐ or heteroaryl‐ 1H‐pyrole‐2,5‐diones. Styryl and merocyanie dyes, and polycyclic pyridazine‐diones as chemiluminophors and succinimides were also obtained from these maleimides with good results.     

DBSA-catalyzed hydrolysis of chain α-oxo ketene dithioacetals in water: Aqueous synthesis of β-ketothioesters

In this paper, we wish to report an environment friendly synthetic method for β-ketothioesters from a dodecylbenzenesulfonic acid (DBSA)-catalyzed hydrolysis reaction of chain α-oxo ketene dithioacetals in water. It was shown that the hydrolysis reaction of chain α-oxo ketene dithioacetals could efficiently occur in the presence of 7.5?mol% DBSA at 100?°C in water, affording the desired β-keto thioesters in excellent yields.     

Experimental and theoretical study of I2-catalyzed dialkenyl oxindoles synthesis from isatins and α-cyano ketene ethylene dithioacetal

An I₂-catalyzed synthesis of dialkenyl oxindoles from isatins and α-cyano ketene ethylene dithioacetal is described. Both electron-withdrawing groups (EWGs) and alkylthio groups exert effects on the reactivities of ketene dithioacetals. Density functional theory (DFT) calculations suggested that the highest negative charge density on the α-carbon of α-cyano ketene ethylene dithioacetal and the largest positive charge on C(3) of the related key intermediate are both responsible for the superior activity of α-cyano ketene ethylene dithioacetal. The cationic intermediate derived from 2-(1,3-dithian-2-ylidene)acetonitrile is the most stable but the least positive, thus the corresponding alkenylhydroxyoxindole is the thermally stable and separable product. Other ketene dithioacetals are less nucleophilic, and their corresponding cationic intermediates are probably not positive enough to enable further transformation.     

Synthesis of Spiro Heterocyclic Ketene Aminals

A method is provided for the synthesis of the previously unknown spiro heterocyclic ketene aminals, 3,9-bis(substituted-methylene)-2,4,8,10-tetraazaspiro[5.5]undecane 3 in moderate to excellent yields by cyclocondensation reaction of ketene dithioacetals 1 with tetrakis(aminomethyl)methane 2.     

One-pot synthesis of polysubstituted pyridine derivatives using ketene dithioacetals

Polysubstituted pyridine derivatives were synthesized by the reaction of ketene dithioacetal, 3,3-bis(methylsulfanyl)methylenemalononitrile 1b, with a variety of active methylene compounds in the presence of either sodium hydroxide or potassium hydroxide as a base in DMSO. This reaction was carried out under economical one-pot reaction conditions (cheap catalyst and solvent) and solved the problem of the odor of methanethiol, commonly derived from reactions of ketene dithioacetals. This is a significant enhancement of GSC (green and sustainable chemistry) in the field of ketene dithioacetal chemistry.     

α-乙酰基二硫缩烯酮的新合成方法

本文采用酸为催化剂，实施了具有代表性的各种烷硫基α,α-二乙酰基二硫缩烯酮的脱乙酰基反应，得到了一条简洁、通用的α-乙酰基二硫缩烯酮的合成路线.用浓硫酸作催化剂，以极高的产率(90%—100%)制得到相应的α-乙酰基二硫缩烯酮.同时，通过控制反应时间，还可以得到硫代乙酰乙酸酯类化合物.     

α—羰基烯酮式环二硫代缩醛类化合物的制备

从具有α-亚甲基的酮出发,利用溶液稀释的方法,提高了用Dieter法合成α-羰基烯酮式环二硫代缩醛类化合物的产率,并用改进方法合成了4个该类化合物。     

Ketene dithioacetals in the aza-Diels-Alder reaction with N-arylimines: a versatile approach to tetrahydroquinolines, 2,3-dihydro-4-quinolones,and 4-quinolones

[reaction: see text] The first successful use of ketene dithioacetals as dienophiles in the aza-Diels-Alder reaction with N-arylimines is described. Among the ketene dithioacetals tested, 1,4-benzodithiafulvenes are most effective in assembling the tetrahydroquinoline core. Subsequent chemical manipulations provide a concise and divergent approach to the synthesis of 2,3-tetrahydroquinolines, 2,3-dihydro-4-quinolones, and 4-quinolones.     

α,α-二乙酰基二硫缩烯酮和芳醛的缩合反应研究

在碱性条件下,α,α-二乙酰基二硫缩烯酮和芳醛的缩合反应受烷硫基的影响.α,α-二乙酰基二苄硫缩烯酮1和芳醛3缩合生成单面缩合脱乙酰基产物α-肉桂酰基二苄硫缩烯酮4;α,α-二乙酰基环二硫缩烯酮2和芳醛3缩合生成双面缩合产物α,α-二肉桂酰基环二硫缩烯酮5.     

Coupling Reaction of Enol Derivatives with Silyl Ketene Acetals Catalyzed by Gallium Trihalides

A cross‐coupling reaction between enol derivatives and silyl ketene acetals catalyzed by GaBr₃ took place to give the corresponding α‐alkenyl esters. GaBr₃ showed the most effective catalytic ability, whereas other metal salts such as BF₃?OEt₂, AlCl₃, PdCl₂, and lanthanide triflates were not effective. Various types of enol ethers and vinyl carboxylates as enol derivatives are amenable to this coupling. The scope of the reaction with silyl ketene acetals was also broad. We successfully observed an alkylgallium intermediate by using NMR spectroscopy, suggesting a mechanism involving anti‐carbogallation among GaBr₃, an enol derivative, and a silyl ketene acetal, followed by syn‐β‐alkoxy elimination from the alkylgallium. Based on kinetic studies, the turnover‐limiting step of the reaction using a vinyl ether and a vinyl carboxylate involved syn‐β‐alkoxy elimination and anti‐carbogallation, respectively. Therefore, the leaving group had a significant effect on the progress of the reaction. Theoretical calculations analysis suggest that the moderate Lewis acidity of gallium would contribute to a flexible conformational change of the alkylgallium intermediate and to the cleavage of the carbon?oxygen bond in the β‐alkoxy elimination process, which is the turnover‐limiting step in the reaction between a vinyl ether and a silyl ketene acetal.     

[Cp2Ln(m-h1:h2-OC(SR)=CPh2 )]2 的合成和表征

[Cp2Ln（μ-SR）]2 was reacted with Ph2C=C=O to yield ketene mono-insertion products [Cp2Ln（μ-η1：η2-OC（SR）=CPh2）]2 [R=Bn, Ln=Yb （1）, Er （2）, Y （3） and R--Ph, Ln=Yb （4）], indicating that the reactions of organolanthanide thiolates with ketenes are independent of the nature of the thiolate ligand and the ketene as well as the reaction condition. These reactions could provide an efficient method for the synthesis of organolanthanide complexes with the a-thiolate-substituted enolate ligand. All these complexes were characterized by elemental analysis and spectroscopic properties and the structure of complex 1 was determined through X-ray single crystal diffraction analysis.