Efficient Synthesis of Eight‐Membered Nitrogen Heterocycles from O‐Propargylic Oximes by Rhodium‐Catalyzed Cascade Reactions

Azocine derivatives were successfully synthesized from O‐propargylic oximes by means of a Rh‐catalyzed 2,3‐rearrangement/heterocyclization cascade reaction. Moreover, the chirality of the substrate was maintained throughout the cascade process to afford the corresponding optically active azocines.     

Efficient synthesis of 3-chloromethyl-2(5H)-furanones and 3-chloromethyl-5,6-dihydropyran-2-ones via the PdCl2-catalyzed chlorocyclocarbonylation of 2,3- or 3,4-allenols

A mild and efficient methodology involving PdCl2-catalyzed chlorocyclocarbonylation of 2,3- or 3,4-allenols with CuCl2 for the synthesis of 3-chloromethyl-2(5H)-furanones and 3-chloromethyl-5,6-dihydropyran-2-ones was developed. This reaction proceeded in a highly regioselective manner, i.e., the chlorine atom was introduced to the terminal position of the allene moiety while the lactone linkage was formed between the center carbon atom of the allene moiety and the hydroxyl oxygen, which was established by the X-ray single crystal diffraction study of gamma-lactone 3p. The highly optically active 3-chloromethyl-2(5H)-furanones could be easily prepared from the readily available optically active 2,3-allenols. A mechanism for this reaction was proposed.     

Enantioselective Synthesis of N‐Phenyl‐dihydropyrano[2,3‐c]pyrazoles via Cascade Michael Addition/Thorpe‐Ziegler Type Cyclization Catalyzed by a Chiral Squaramide

Enantioselective synthesis of biologically active dihydropyrano[2,3‐c]pyrazoles has been achieved through a squaramide‐catalysed Michael addition/Thorpe‐Ziegler type cyclization cascade reaction between arylidenepyrazolones and malononitrile. A series of optically active dihydropyano[2,3‐c]pyrazoles were obtained in excellent yields (up to 99%) and moderate to good enantioselectivities (up to 79% ee) under mild reaction conditions.     

A highly stereoselective synthesis of aldols employing the Reformatsky reaction of 3-(2-bromopropionyl)-2-oxazolidone derivatives with various aldehydes

The title reactions of sterically crowded 2-oxazolidone derivatives with achiral aldehydes in the presence of zinc dust were found to give various 2,3- -aldols as major products (at most, 2,3- :2,3- =98:2). While a 2,3- -3,4- -aldol could be similarly produced in a highly stereoselective manner, application of the explored reaction to asymmetric synthesis of optically active 2,3- -aldols was found to be unpromising.     

An efficient double 1,2-addition reaction of 2,3-allenoates with allyl magnesium chloride

In this paper, it was reported that double 1,2-addition reaction of 2,3-allenoates with allyl magnesium chloride at room temperature in the absence of any transition metal catalyst provides an efficient method for the synthesis of tertiary alpha-allenols. The optically active allenol could be prepared from the reaction of the optically active 2,3-allenoate without obvious racemization of the axial chirality. Under different reaction conditions, cyclization reactions of alpha-allenol 2i prepared have been studied for the synthesis of different 2,5-dihydrofuran derivatives.     

A facile synthesis of some thieno/furo‐[2,3‐d]pyrimidine‐2‐yl‐thioacetic acid derivatives

The reaction of 2‐(α‐chloroacetamido)‐3‐cyano‐4,5‐disubstituted thiophenes/furanes with ammonium thiocyanate in methanol or ethanol afforded methyl or ethyl (4‐amino‐5,6‐disubstituted thieno/furo[2,3‐d]‐pyrimidine‐2‐yl)thioacetates in good yields.     

Enantioenriched dihydropyrones from beta-lactone templates

[reaction: see text] Optically active 4-substituted 2-oxetanones provide conduits for preparing 2,3-dihydro-4H-pyrone heterocycles. Enantioenriched beta-lactones are prepared by asymmetric catalytic acyl halide-aldehyde cyclocondensation reactions. Hydrazone anion-mediated beta-lactone ring opening and ensuing cyclization-dehydroamination of the derived beta-ketohydrazone afford the desired dihydropyrones (68-81%). Optimized lactone ring-opening-cyclization reaction conditions render a variety of optically active 4-substituted-2-oxetanones as effective precursors to enantioenriched 2,3-dihydro-4H-pyrones.     

PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols: an efficient synthesis of 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives

A PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols was observed to provide an efficient route to 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives. By using the easily available optically active starting materials, 2,5-dihydrofurans with high enantiopurity may be prepared. A Pd(II)-catalyzed mechanism was also discussed.     

Synthesis of new 1,3-thiazole derivatives from 2(5)-hydroxyalkyl-1,3-thiazole-5(2)-carbaldehydes

Reactions of substituted 2-hydroxyalkyl-1,3-thiazole-5-carbaldehydes and 5-hydroxyalkyl-1,3-thiazole-2-carbaldehydes with phenylhydrazine, isoniazid, N-substituted rhodanines were performed as well as Biginelli reaction with acetoacetic ester and urea. As a result, new 1,3-thiazole derivatives were obtained. They are of interest as potential bioactive substances.     

A Practical Synthesis of Chiral 3-Chloro-2-hydroxyalkanoates and 2,3-Epoxyalcohols

Asymmetric reduction of 3-chloro-2-oxoalkanoates with baker's yeast gave optically active 3-chloro-2-hydroxyalkanoates with ≥95% e.e. in most cases, which were converted to optically active 2,3-epoxyalcohols with ≥78.0% e.e.     

Pd(II)-catalyzed oxidative dimeric cyclization-coupling reaction of 2,3-allenoic acids: an efficient synthesis of bibutenolide derivatives

Three sets of convenient catalytic systems have been developed for the oxidative dimeric cyclization coupling of differently substituted 2,3-allenoic acids catalyzed by Pd(II), affording bibutenolides that are not otherwise readily available. The advantages and disadvantages of these systems are discussed. Although the diastereoselectivity for the bicyclization of racemic 2,3-allenoic acids is low, excellent diastereoselectivity was realized in the bicyclization reaction of optically active 2,3-allenoic acids, leading to the optically active bibutenolides in high yields and ee. Based on a mechanistic study, it is believed that the reaction may proceed by means of a double oxypalladation and reductive elimination to yield butenolide 3 and Pd(0) species, which may be reoxidized to the catalytically active Pd(II) species in the presence of alkyl iodide/air, metallic iodide/air, or benzoquinone.     

Facile and efficient synthesis of lactols by a domino reaction of 2,3-epoxy alcohols with a hypervalent iodine(III) reagent and its application to the synthesis of lactones and the asymmetric synthesis of (+)-tanikolide

The domino reaction of 2,3-epoxy-1-alcohol derivatives, namely tetrasubstituted 2,3-epoxy-1-alcohols and 2- or 3-alkyl trisubstituted 2,3-epoxy-1-alcohols, with PhI(OCOCF(3))(2) in the presence of H(2)O is described in detail. In this reaction, several types of lactol derivatives can be directly obtained from the 2,3-epoxy-1-alcohol derivatives in a single operation. The obtained lactols were successively converted into the corresponding lactones. This reaction is applicable to the construction of optically active lactone compounds. The asymmetric total synthesis of (+)-tanikolide, an antifungal marine natural product, has been effectively achieved by using this reaction.     

Synthesis of 2-(ω-aminoalkyl)imidazolin-4-ones by ring chain transformation of lactam derivatives with α-aminoamides

Reaction of N-methylamides of biogenic (S)-α-amino acids 3 with lactam acetals 1 or lactim ethers 2 gives three types of products, i.e. N-methyl-α-lactamiminoamides 5 by condensation, 2-(ω-aminoalkyl)imidazolin-5-ones 7 or 2-(ω-lactamimmoalkyl)imidazolin-4-ones 8 by ring chain transformation. All products represent novel optically active derivatives of biogenic α-aminoacids.     

Studies on Cu(I)-catalyzed synthesis of simple 3-substituted 1,2-allenes and optically active 2-substituted secondary 2,3-allenols

The sequential treatment of terminal alkynes or propargylic alcohols with n-BuLi and MOMCl afforded the corresponding propargylic methyl ethers, which would react with primary alkyl Grignard reagents under the catalysis of CuBr to afford 3-substituted 1,2-allenes or 2-substituted secondary 2,3-allenols, respectively. The reaction may be applied to the synthesis of optically active 2-substituted secondary 2,3-allenols with up to >99% ee without any protection to the free hydroxyl group in the starting 4-hydroxy-2-alkynyl methyl ethers.     

One-pot construction of aza- or oxa-bridged benzocycloheptanes from readily available 2,3-allenyl malonates or 2,3-allenols and o-iodobenzaldehyde or imine

A Pd(OAc)(2)-catalyzed reaction of 2,3-alkadienyl malonates or 2,3-allenols with o-iodobenzaldehyde or its N-tosyl imine occurred smoothly in MeCN at 80 °C to form the oxa- or aza-bridged benzocycloheptane derivatives with important biological potential. With the optically active 2,3-allenols, the absolute configurations of all the three chiral centers have been conveniently established.     

Mechanistic switch leading to highly efficient chirality transfer in Pd(0)-catalyzed coupling-cyclization of aryl iodides with 1:1 acid-base salts of 2,3-allenoic acids and L-(-)-cinchonidine or D-(+)-/L-(-)-alpha-methylbenzylamine. Enantioselective synthesis of highly optically active 3-aryl polysubstituted butenolides

An efficient methodology provides an easy access to highly optically active polysubstituted butenolides starting from aryl halides and 1:1:salts of optically active 2,3-allenoic acid-base via an oxidative addition-coordinative cyclization-reductive elimination mechanism, which led to the high efficiency of this chirality isomerization reaction.     

Efficient synthesis of 4-(3'-furanyl)butenolide derivatives via PdII-catalyzed oxidative heterodimeric cyclization reaction of 2,3-allenoic acids and 1,2-allenyl ketones

The oxidative cyclization/dimerization reaction between two classes of allenes with different functionalities was reported to provide an efficient route to polysubstituted 4-(3'-furanyl)-2(5H)-furanones, which are not readily available from the known methods. The highly optically active butenolides could be easily formed from the optically active 2,3-allenoic acids, which was obtained conveniently through chiral resolution with optically active amines, that is, cinchonidine or alpha-methyl benzylamine. A mechanistic study showed that the reaction proceeded via a matched double oxypalladation-reductive elimination process. The Pd(II) species may be regenerated via the subsequent cyclometallation of two equivalents of 1,2-allenyl ketones with Pd(0) and protonlysis of Pd enolates formed with the in situ generated HCl.     

Optically active thiophenes via an organocatalytic one-pot methodology

A general methodology for the synthesis of trisubstituted, optically active thiophenes by an organocatalytic one-pot reaction cascade is presented. The target products are synthesized in good yields (up to 92%) and with excellent enantioselectivities (up to 98% ee). Importantly, based on practical and easily available starting materials, the presented methodology can be conducted under mild reaction conditions. To further elucidate the generality, the synthesis of optically active thienoindoles, as well as selenophenes, is also demonstrated.     

Cationic Pd(II)-catalyzed enantioselective cyclization of aroylmethyl 2-alkynoates initiated by carbopalladation of alkynes with arylboronic acids

A cationic palladium(II)-catalyzed enantioselective intramolecular addition of vinylpalladium species to ketones initiated by the carbopalladation of alkynoates under mild conditions without a Pd(II)/Pd(0) redox system was developed with high yield and enantioselectivity. This cascade reaction provides an efficient method for the construction of optically active hydroxylactones.     

Cycloaddition of homochiral dihydroimidazoles: a 1,3-dipolar cycloaddition route to optically active pyrrolo[1,2-a]imidazoles

N-Alkylation of optically active 1-benzyl-4-phenyl-4,5-dihydroimidazole with active alkyl halides and treatment of the so-formed 4,5-dihydroimidazolium ions with DBU in the presence of a range of electron-deficient alkene dipolarophiles, constitutes a 'one-pot' cascade terminating in a 1,3-dipolar cycloaddition reaction that affords optically active pyrrolo[1,2-a]imidazoles. Three bonds of the so-formed pyrrolidine moiety are constructed in this cascade. The cycloaddition follows an endo approach of dipole and dipolarophile with anti geometry of the dipole and facial selectivity derived from the phenyl substituent. Inter- and intramolecular cycloaddition modes are observed.