Synthesis of 3‐Carbamoyl β‐Lactams via Manganese(III)‐Promoted Cyclization of N‐Alkenylmalonamides

Manganese(III)‐promoted cyclization of N‐alkenylmalonamides (=N‐alkenylpropanediamides) gave 3‐(aryl/(alkylamino)carbonyl) β‐lactams as well as 3‐(aryl/(alkylamino)thiocarbonyl) β‐lactams. The relative configuration of the obtained products was unambiguously determined by X‐ray crystallography. The proposed method is very useful for the one‐pot synthesis of a number of 3‐(aryl/(alkylamino)carbonyl) β‐lactams, especially those containing an amino(thiocarbonyl) moiety, which are not selectively accessible by other methods.     

Stepwise Mechanism of Hydroxide Ion Catalyzed Cyclization of Uridine 3′‐Thiophosphates

Diastereoisomeric isopropyl‐, 2‐ethoxyethyl‐, 2,2‐dichloroethyl‐ and 2,2,2‐trichloroethyl uridine 3′‐thiomonophosphates, 1a – 1d , respectively, have been synthesized, and their hydrolyses in aqueous alkali at 25° have been followed by HPLC. According to the time‐dependent product distributions obtained, the alkyl phosphorothioates 1a – 1d undergo cleavage to uridine 2′‐ and 3′‐thiophosphates, 7a and 7b , respectively, via a uridine 2′,3′‐cyclic thiophosphate ( 6 ). The rate of the hydroxide ion‐catalyzed cyclization of both (R_P)‐ and (S_P)‐diastereoisomer is highly dependent on the polar nature of the leaving group, the β_lg values being ?1.23±0.03 and ?1.24±0.03, respectively. Brønsted dependence of the second‐order rate constants (k_OH [dm³ mol^?1 s^?1]) on the pK_a values of the leaving alcohols shows a convex breakpoint on going from alkyl esters 1a – 1d to aryl esters studied earlier. This may be considered as a strong evidence for a stepwise mechanism, where the formation and breakdown of the phosphorane intermediate is the rate‐limiting step with aryl and alkyl esters, respectively.     

A New Cyclization/Decarboxylation Reaction of Isatins with Acyl Chlorides for the Facile Synthesis of 3‐Alkenyl‐Oxindoles

The first cyclization/decarboxylation reaction of isatins with acyl chlorides promoted by 4‐dimethylaminopyridine (DMAP) was described and a series of desired 3‐alkenyl‐oxindoles were obtained in good yields (up to 80%) and E/Z selectivities (up to 6.4/1). This protocol provided a new and feasible access to 3‐alkenyl‐oxindoles.     

Synthesis of Halogenated α,β‐Unsaturated γ‐Butyrolactone Derivatives by Triphenylphosphine‐Catalyzed Cyclization of α‐Halogeno Ketones with Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates)

A Ph₃P‐catalyzed cyclization of α‐halogeno ketones 2 with dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) 3 produced halogenated α,β‐unsaturated γ‐butyrolactone derivatives 4 in good yields (Scheme 1, Table). The presence of electron‐withdrawing groups such as halogen atoms at the α‐position of the ketones was necessary in this reaction. Cyclization of α‐chloro ketones resulted in higher yields than that of the corresponding α‐bromo ketones. Dihalogeno ketones similarly afforded the expected γ‐butyrolactone derivatives in high yields.     

Copper‐Catalyzed Electrophilic Cyclization of N‐Propargylamines with Sodium Sulfinate for the Synthesis of 3‐Sulfonated Quinolines

A convenient and effective protocol for the synthesis of 3‐sulfonated quinolines via copper‐catalyzed electrophilic cyclization of N‐propargylamines has been developed, in which cheap and stable sodium sulfinates were utilized as green sulfonylation reagents. This cascade transformation involves radical addition, cyclization and dehydrogenative aromatization processes in a one‐pot reaction under mild conditions.     

Copper‐Free Sonogashira Coupling of Acid Chlorides with Terminal Alkynes in the Presence of a Reusable Palladium Catalyst: An Improved Synthesis of 3‐Iodochromenones (=3‐Iodo‐4H‐1‐benzopyran‐4‐ones)

Pd/C is used as an efficient catalyst for the copper‐free Sonogashira coupling of acid chlorides and terminal alkynes to afford ynones in high yields (Tables 1 and 3). Cyclization of (2‐methoxyaryl)‐substituted ynones induced by I₂/ammonium cerium(IV) nitrate (CAN) at room temperature gave 3‐iodochromenones (=3‐iodo‐4H‐1‐benzopyran‐4‐ones) in excellent yield (Table 4).     

A Novel and Regiospecific Synthesis of 1‐Aryl‐1H‐benzotriazoles via Copper(I)‐Catalyzed Intramolecular Cyclization Reaction

1‐Aryl‐1H‐benzotriazole derivatives were synthesized via intramolecular cyclization of easily obtained triazenes, using CuI as the catalyst, DMSO as the solvent, t‐BuONa as the base, and 1,10‐phenanthroline as the ligand, in up to 97% yield. The synthesis is regiospecific and functional group‐tolerant.     

A Novel Synthesis of Isoflavones via Copper(I)‐Catalyzed Intramolecular Cyclization Reaction

Isoflavone derivatives were synthesized via intramolecular cyclization of 3‐(2‐bromophenyl)‐3‐oxopropanal derivatives, using CuI as the catalyst, 2‐picolinic acid (=pyridine‐2‐carboxylic acid) as the ligand, K₂CO₃ as the base, and DMF as the solvent, in up to 96% yield. The synthesis is functional group‐tolerant.     

Cyclization vs. Elimination Reactions of 5‐Aryl‐5‐hydroxy 1,3‐Diones: One‐Pot Synthesis of 2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones

2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones were prepared in one step by cyclocondensation of 1,3‐diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very important to avoid elimination reactions of the 5‐aryl‐5‐hydroxy 1,3‐diones formed as intermediates. The TiCl₄‐mediated cyclization of a 2‐aryl‐2,3‐dihydro‐4H‐pyran‐4‐one with 1,3‐silyloxybuta‐1,3‐diene resulted in cleavage of the pyranone moiety and formation of a highly functionalized benzene derivative.     

Regioselective Synthesis of 4‐(Arylsulfanyl)‐2‐hydroxyhomophthalates by [4+2] Cycloaddition of 3‐(Arylsulfanyl)‐1‐(trimethylsilyloxy)buta‐1,3‐dienes with Dimethyl Penta‐2,3‐dienedioate

The [4+2] cycloaddition of 3‐(arylsulfanyl)‐1‐(trimethylsilyloxy)buta‐1,3‐dienes with dimethyl penta‐2,3‐dienedioate provides a convenient and regioselective approach to a variety of 4‐(arylsulfanyl)‐2‐hydroxyhomophthalates.     

Synthesis of 3,5‐Diarylcyclohex‐2‐enones by NH4Cl/HCl‐Catalyzed Cyclization and Deacetylation of 4‐Acetylhexane‐1,5‐diones

A new route for the synthesis of 3,5‐diarylcyclohex‐2‐enones is reported. The 4‐acetyl‐1,3‐diarylhexane‐1,5‐diones were obtained by the addition of pentane‐2,4‐dione to chalcones. The reaction of 4‐acetyl‐1,3‐diarylhexane‐1,5‐diones with NH₄Cl/HCl in EtOH under reflux conditions gave the 3,5‐diarylcyclohex‐2‐enones in good yields. All synthesized compounds were characterized by spectroscopic methods (¹H‐, ¹³C‐NMR, and IR), and elemental analyses.     

A Simple Synthesis of Polyfunctionalized 4‐Aminopyrazolidin‐3‐ones as ‘Aza‐deoxa’ Analogs of D‐Cycloserine

A simple five‐step synthesis of fully substituted (4RS,5RS)‐4‐aminopyrazolidin‐3‐ones as analogs of D ‐cycloserine was developed. It comprises a two‐step preparation of 5‐substituted (4RS,5RS)‐4‐(benzyloxycarbonylamino)pyrazolidin‐3‐ones, reductive alkylation at N(1), alkylation of the amidic N(2) with alkyl halides, and simultaneous hydrogenolytic deprotection/reductive alkylation of the primary NH₂ group. The synthesis enables an easy stepwise functionalization of the pyrazolidin‐3‐one core with only two types of common reagents, aldehydes (or ketones) and alkyl halides. The structures of products were elucidated by NMR spectroscopy and X‐ray diffraction.     

Incorporation of an Allene Unit into α‐Pinene via β‐Elimination

The two double‐bond isomers 3‐iodo‐2,6,6‐trimethylbicyclo[3.1.1]hept‐2‐ene ( 6b ) and 3‐iodo‐4,6,6‐trimethylbicyclo[3.1.1]hept‐2‐ene ( 11 ) were synthesized by reacting 2,6,6‐trimethylbicyclo[3.1.1]heptan‐3‐one ( 9 ) with hydrazine, followed by treatment with I₂ in the presence of Et₃N. Treatment of 11 with t‐BuOK as base in diglyme at 220° resulted in the formation of 9 and 6,6‐dimethyl‐4‐methylidenebicyclo[3.1.1]hept‐2‐ene ( 12 ). For the formation of 9 , the cyclic allene 7 is proposed as an intermediate. Treatment of the second isomer, 6b , with t‐BuOK at 170° gave rise to the diene 12 and the dimerization product 17 . The underlying mechanism of this transformation is discussed. On the basis of density‐functional‐theory (DFT) calculations on the allene 7 and the alkyne 15 , the formation of the latter as the intermediate was excluded.     

Tandem Hydroformylation/Reductive Amination of 3‐Allyl‐2‐methylquinazolin‐4(3H)‐one

The 3‐allyl‐2‐methylquinazolin‐4(3H)‐one ( 1 ), a model functionalized terminal olefin, was submitted to hydroformylation and reductive amination under optimized reaction conditions. The catalytic carbonylation of 1 in the presence of Rh catalysts complexed with phosphorus ligands under different reaction conditions afforded a mixture of 2‐methyl‐4‐oxoquinazoline‐3(4H)‐butanal ( 2 ) and α,2‐dimethyl‐4‐oxoquinazoline‐3(4H)‐propanal ( 3 ) as products of ‘linear’ and ‘branched’ hydroformylation, respectively (Scheme 2). The hydroaminomethylation of quinazolinone 1 with arylhydrazine derivatives gave the expected mixture of [(arylhydrazinyl)alkyl]quinazolinones 5 and 6 , besides a small amount of 2 and 3 (Scheme 3). The tandem hydroformylation/reductive amination reaction of 1 with different amines gave the quinazolinone derivatives 7 – 10 . Compound 10 was used to prepare the chalcones 11a and 11b and pyrazoloquinazolinones 12a and 12b (Scheme 4).     

Molybdenum‐ and Tungsten‐Based Coordination Polymers as Catalysts for an Efficient and Rapid Synthesis of Hexahydro‐5‐oxoquinoline‐3‐carboxylates and 1,4‐Dihydropyridine‐3,5‐dicarboxylates

Hexahydro‐5‐oxoquinoline‐3‐carboxylates and 1,4‐dihydropyridine‐3,5‐dicarboxylates were synthesized efficiently and rapidly (2 min) in the presence of molybdenum‐ and tungsten‐based coordination polymers [M(Bu₃Sn)₂O₄)]_n (M=Mo or W) as catalysts (Schemes 1 and 2; Tables 2 and 3). The products were formed at room temperature in excellent yields (90–98%). The catalysts worked under heterogeneous conditions and were recyclable. The earlier reports for the application of these polymers to conduct organic synthesis are limited. The present method explores a new and useful application of these catalysts.     

Synthesis of Substituted 1,3‐Diene Synthetic Equivalents by a Ru‐Catalyzed Diyne Hydrative Cyclization

Catalyzed by [CpRu(CH₃CN)₃]PF₆, the hydrative cyclization of dipropargylic sulfone substrates provides an effective way to synthesize highly functionalized substituted 3‐sulfolenes. The amount of water is crucial for the reactivity of this cycloisomerization reaction. The scope and limitations of the Ru‐catalyzed cycloisomerization are discussed. A marked ketone‐directing effect was observed for the first time in ruthenium‐catalyzed cyclizations. A plausible mechanism for the ketone‐directed cycloisomerization is also rationalized. The utility of this method was demonstrated by both sulfur dioxide extrusion of the 3‐sulfolenes to afford 1,3‐dienes and subsequent inter‐ or intramolecular Diels–Alder reactions.     

Synthesis of 9,9‐Disubstituted 9H‐Pyrrolo[1,2‐a]indoles by Hydriodic Acid‐Catalyzed Cyclization of 1‐[2‐(1‐Aryl(or methyl)ethenyl)phenyl]‐1H‐pyrroles

A novel method is reported for the synthesis of 9,9‐disubstituted 9H‐pyrrolo[1,2‐a]indoles. Cyclization of 1‐[2‐(1‐aryl(or methyl)ethenyl)phenyl]‐1H‐pyrroles, which can be easily prepared from 2‐(1‐aryl(or methyl)ethenyl)anilines, proceeds smoothly, in general, at 0° in the presence of a catalytic (or an equimolar) amount of HI in MeCN to provide the desired products.     

Superacid‐Catalyzed Cyclization of Methyl (6Z)‐Geranylfarnesoates

Methyl (2Z,6Z,10E,14E)‐ ( 3 ) and methyl (2E,6Z,10E,14E)‐geranylfarnesoate ( 4 ) were prepared, and then individually cyclized in the presence of the superacid FSO₃H. In the case of substrate 3 , the scalaranic ester 9 (26%) and the cheilanthanic ester 10 (39%) were isolated. Under the same conditions, substrate 4 afforded a mixture of the corresponding stereoisomers 11 (25%) and 12 (63%). The observed product selectivity supports that the internal, (6Z)‐configured C?C bond in these and other biologically relevant substrates plays an essential role in the cyclization process.     

Regioselective Synthesis of Aurone Derivatives via PBu3‐Catalyzed Cyclization of 2‐Alkynoylphenols

Aurone derivatives were synthesized in good to high yields by PBu₃‐catalyzed intramolecular 5‐exo cyclization of 2‐alkynoylphenols. The reaction proceeds in high regioselectivity without forming 6‐endo cyclization products.