Synthesis of fused or not β-lactam-biaryl hybrids by free radical aryl-aryl coupling of 2-azetidinone-tethered haloarenes

cis and trans-Aryl-2-azetidinone-tethered haloarenes can be stereoselectively prepared using the ketene-imine cyclization. These β-lactam-tethered haloarenes were used for the regiocontrolled preparation of β-lactam-biaryl hybrids including fused tetracyclic biaryl-2-azetidinones as well as C4-dearylated not fused biphenyl‐2-azetidinones via aryl-aryl radical cyclization and/or rearrangement. Alternatively, trans-dibenzocarbacephems could be stereoselectively prepared, both in racemic and enantiopure form, through the Staudinger reaction between phenanthridine and activated ketenes.     

Influence of ring fusion stereochemistry on the stereochemical outcome in photo-induced Diels–Alder reaction of fused bicycloheptenone derivatives

Photo-isomerization of cis-cycloheptenone fused to a ring with a defined stereochemistry at the ring fusion to its trans-stereoisomer and in situ Diels–Alder reaction with cyclic and acyclic dienes have been investigated. The reaction was found to proceed through one of the two possible isomerized trans-enones that produce the thermodynamically more stable adduct with a trans-fused seven-membered ring system. This protocol has been employed to construct a tetracycle with trans-fused 6-7 ring system, the core structure present in several terpenes. The observed selectivity has been supported by computational method.     

Simple and mild stereoselective O-glycosidation using 1,2-anhydrosugars under neutral conditions

The ring opening of α-d-1,2-anhydrohexapyranoses with phenols proceeded smoothly in ethyl acetate (neutral conditions) in the absence of metal ion catalysts or additives to stereoselectively furnish 1,2-cis-α-aryl glycosides as the major product and 1,2-trans-β-aryl glycosides as the minor product in good yields. Under similar conditions, this ring opening reaction with alcohols afforded exclusively β-alkyl glycosides in excellent yields.     

Synthesis of functionalized and fused furans and pyrans from the Morita–Baylis–Hillman acetates of nitroalkenes

The Morita–Baylis–Hillman (MBH) acetates derived from nitroalkenes and ethyl glyoxylate have been transformed in one pot at room temperature to highly fused and functionalized furans and pyrans in good to excellent yield. The reaction involves a cascade Michael–oxa-Michael addition of β-dicarbonyl compounds to the MBH acetates in the presence of an amine base such as DABCO. An unusual switching of selectivity in the oxa-Michael addition from 5-exo-trig to 6-endo-trig was observed when the β-dicarbonyl compound was changed from acyclic or six-membered ring cyclic to five-membered ring cyclic system.     

Asymmetric synthesis of 1,3-thiazolidine-derived spiro-β-lactams via a Staudinger reaction between chiral ketenes and imines

Enantiomerically pure 1,3-thiazolidine-derived spiro-β-lactams were stereoselectively synthesised by means of a Staudinger ketene–imine reaction starting from optically active N-Boc-1,3-thiazolidine-2-carboxylic acid derivatives and imines. The reactions were stereoselective and afforded spiro-β-lactams with a relative trans-configuration. The absolute configuration of the new stereocentres was assigned on the basis of the well-accepted mechanism and confirmed by means of the X-ray crystal structure analysis. The spiro-β-lactams were transformed into enantiomerically pure chiral monocyclic β-lactams by opening the thiazolidine ring and recovering the chiral auxiliary.     

A facile preparation of trans-1,2-cyclopropanes containing p-trifluoromethylphenyl group and its application to the construction of pyrazole and cyclopropane ring fused pyridazinone derivatives

A facile methodology for the preparation of highly functionalized trans-1,2-cyclopropanes containing p-trifluoromethylphenyl group 3 is described. Arsonium bromides 1 reacted with electron-deficient olefins 2 in the presence of K₂CO₃ to provide 3 stereoselectively in moderate to good yields. This process has been successfully applied to the construction of cyclopropane ring fused pyridazinone derivatives 4 or pyrazole derivatives 5.     

Thallium(III) Nitrate Mediated Ring Contraction of 2‐Aryl‐1,2,3,4‐tetrahydro‐4‐quinolones: Stereoselective Synthesis of trans Methyl 2‐Aryl‐2,3‐dihydroindol‐3‐carboxylates

The ring contraction of N‐acetyl‐2‐aryl‐1,2,3,4‐tetrahydro‐4‐quinolones 1a–d with thallium(III) nitrate in trimethyl orthoformate afforded stereoselectively trans methyl N‐acetyl‐2‐aryl‐2,3‐dihydroindol‐3‐carboxylates 5a–d by oxidative rearrangement of aryl ring A.     

A straightforward double intramolecular cyclization of dibenzyl dichalcogenols into a triple bond

The intramolecular cyclizations of four types of dibenzyl chalcogenols, which contained one or two ethynyl groups, were carried out. Either the double 5-exo or 6-endo-dig mode ring closure reaction regio- and stereoselectively proceeded to give the corresponding symmetrical bis(benzo[c]chalcogenophene) or bis(isochromene) derivatives from the dibenzyl chalcogenols having a diyne moiety. In contrast, the regioselective tandem 5-exo-dig mode intramolecular ring closure reactions of dibenzyl thiol and selenol having a mono-yne into a triple bond gave the trans-biisobenzothiophene and selenophene as the sole product. However, the similar cyclization of dibenzyl tellurol proceeded in both tandem 5-exo and 6-endo-dig modes to afford the trans-biisobenzotellurophene and ditellurachrysene in good yields with the ratio of 1:1. The X-ray structural analysis of these novel compounds is also presented.     

Efficient synthesis of cis-thiazolidinethiones derived from ephedrines

The reaction of chlorodeoxypseudoephedrine or chlorodeoxynorpseudoephedrine hydrochlorides with sodium dithiocarbonate in stirring ethanol at 0 °C to stereoselectively afford the corresponding cis-thiazolidinethiones in good yields (81% and 95%) is reported. The in situ formation of a cis-aziridine to explain the presence of trans-thiazolidinethione as a side product is proposed when the same reaction was carried out at room temperature. In addition, a 70:30 mixture of trans-isomers of a thiazolidinethione/isothiazolidinethione was formed when a cis-aziridine NH was reacted with carbon disulfide in refluxing ethanol. The analogous reaction with cis-aziridine N-Me stereoselectively affords the corresponding cis-thiazolidinethione. The ¹H and ¹³C NMR data of the thiazolidinethiones were assigned. cis-3,4-Dimethyl-5-phenylthiazolidine-2-thione was crystallized from ethanol and its X-ray diffraction structure was analyzed.     

Ring transformations of heterocyclic compounds. XXI. Diastereoselective built‐up of an aroylcyclohexadiene moiety as second spiro‐connected ring at spiroindolines by pyrylium ring transformation

2,4,6‐Triarylpyrylium perchlorates 1 react with methyleneindolines 3 in situ generated from the corresponding methylindolium salts 2 , which are spiro‐fused with a cycloalkane, benzanellated cycloalkene or a heterocyclic system. These diastereoselective 2,5‐[C₄+C₂] pyrylium ring transformations are carried out in the presence of triethylamine/acetic acid in boiling ethanol to give the dispiroindolines 4 with a trans configuration of the more bulky substituents at the cyclohexadiene ring. By the same type of transformation the dispiro compounds 7/10 with an additional fused benzene ring are obtained from the pyrylium salt 1a and 6/9 , the benzo‐fused analogues of 3 . Spectroscopic data of the transformation products as well as their mode of formation are discussed.     

Conformations of fused cycloalkanes in organometallic complexes : IV. The crystal and molecular structure of tricyclo-[6.4.0.02.7]dodeca-3,5-dienetricarbonyliron

The precise molecular structure of the title compound has been determined by single crystal X-ray diffractometry. It consists of a cyclohexadiene ring fused at the 5 and 6 positions to a cyclobutane ring which is in turn fused to a cyclohexane ring. The two six-membered rings are trans to each other with respect to the shared four-membered ring. The Fe(CO)₃ moiety is bound in the usual way to the conjugated diene portion of the cyclohexadiene ring. The feature of greatest interest is the mutual influence of the conformations of the two fused cycloalkane rings, whose intrinsically preferred conformations are mutually incompatible. Under the influence of the fused cyclohexadiene ring the C₄ ring would tend to be planar, while the cyclohexane ring would tend, of itself, to have a chair conformation. The actual result is a compromise, with the C₄ ring being folded by 15° along its diagonal and the C₆ ring having a conformation intermediate between planarity and a chair. Crystallographic data: space group, P2₁, Z = 2. Unit cell dimensions at 3°C are a = 6.176(1), b = 11.307(2), c = 9.781(2) Å and β = 92.89(2)°. A set of 1733 reflections having 2θ(Mo-K_α) < 63.7° and I > σ(I) was refined to convergence (R₁ = 0.055; R₂ = 0.034) with hydrogen atoms refined isotropically and all others anisotropically.     

Intramolecular Hetero‐Diels–Alder Reactions Catalyzed by BiCl3: Stereoselective Synthesis of Benzo‐Annelated Decahydrofuro[3,2‐h][1,6]naphthyridine Derivatives

A novel, efficient synthesis of a series of functionalized, benzo‐annelated decahydrofuro[3,2‐h][1,6]naphthyridine derivatives 3 has been achieved. The protocol is based on the intramolecular hetero‐Diels–Alder (IMHDA) reaction of in situ formed imines derived from an N‐prenylated sugar aldehyde 1 and different aromatic amines 2 in the presence of bismuth(III) chloride as catalyst. The reactions could be run under very mild conditions at room temperature, and were complete within 30 min, affording exclusively and stereoselectively the corresponding trans‐fused products 3 in good‐to‐excellent yields (Table).     

Molecular recognition in the palladium complex promoted asymmetric synthesis of a keto-ester heterofunctionalized P-chiral phosphine

A chiral organopalladium complex promoted asymmetric Diels–Alder reaction between 1-phenyl-3,4-dimethyl-phosphole and methyl-trans-4-oxo-2-pentenoate gives the corresponding keto-carboxylate heterofunctionalized P-chiral phosphine ligand in which the keto group is stereoselectively located in the exo position of the phosphanorbornene skeleton.     

SYNTHESIS AND CONFIGURATIONAL STUDIES OF ARYL CYCLOPROPYL SULFONES

Abstract

The cycloaddition of arylthiocarbenes to styrene gave stereospecifically cis?1-(arylthio)-2-phenylcyclopropanes, which were subsequently oxidized to the corresponding sulfones. The cyclopropanation of α,β-unsaturated sulfones with dimethylsulfonium methylide yielded stereoselectively trans?1-(arylsulfonyl)-2-arylcyclopropanes. The configurational assignments of these compounds have been arrived at on the basis of IR and PMR spectral data. Chemical shifts for ring protons and other substituents reveal that all the substituents tend to cause protons cis to them to appear at higher fields than those trans to them. This has been used as a criterion to distinguish between cis and trans aryl cyclopropyl sulfones.     

γ-Heteroatom directed stereocontrolled Staudinger cycloaddition reaction of vinylketenes and imines

Vinylketenes possessing a γ-heteroatom, on Staudinger cycloaddition reaction with imines gave trans-3-vinyl-β-lactams in very good yields. The vinyl side chain stereoselectively adopts the Z-configuration in the transition state to stabilize the vinylketene and produces, exclusively, trans-3-vinyl-β-lactams.     

Reactions of 2,3,5-trichloro-4-hydroxycyclopent-2-en-1-one with dimethyl-and diethylamines and benzenethiol. Some aspects of stereochemical assignments in cyclopentenone chlorohydrins

trans-2,3,5-Trichloro-4-hydroxycyclopent-2-en-1-one reacted with dimethyl-and diethylamines and sodium benzenethiolate in methanol to give the corresponding products of chlorine replacement at the sp ²-hybridized C³ atom via AdNE mechanism. The reactions were characterized by partial trans-cis isomerization. Assignment of configuration of isomeric cyclopentenone chlorohydrins on the basis of the NMR data is discussed.     

Stereoselective synthesis of optically active cyclopenta[c]pyrans and cyclopenta[c]furans by the intramolecular Pauson–Khand reaction

An intramolecular Pauson–Khand reaction of enynes derived from homoallyl, homopropargyl, and allyl alcohols is described. 2-Heteroaryl-substituted homoallyl, homopropargyl, and allyl alcohols are easily and efficiently resolved through enzymatic resolution in high ee (91–99%) and with a known stereochemistry. Each enantiomerically enriched enyne derived from homoallyl and homopropargyl alcohols affords the conformationally most stable diastereomeric cyclopenta[c]pyran ring system as the sole product, whereas enantiomerically enriched enynes derived from allyl alcohols give a diastereomeric cis:trans mixture of the cyclopenta[c]furan ring system.     

Configurational inversion and hexachloroethane chlorination of α-sulfonylcarbanions

The cis fused bicyclic sulfones 1a, 1c and 3a are lithiated in benzene with n-butyllithium under concomitant cis/trans isomerization of the ring fusion, involving intramolecular proton transfer. H/D exchange of the three α-hydrogens in protic solvents proceeds with retention of configuration. The lithiated sulfones are chlorinated with hexachloroethane (HCE) and show a strong preference for introduction of halogen at an equatorial α-position.     

Adiabatic <Emphasis Type="Italic">trans-cis</Emphasis> photoisomerization and photocyclization of 8-styrylquinoline

Kinetics of the photocyclization of trans-8-styrylquinoline into 10a,10b-dihydronaphtho[1,2-h]quinoline (4-azachrysene) was studied in hexane. It was found that in addition to the expected two-step (two-quantum) route with trans-cis photoisomerization occurring in the first step with a quantum yield of φ_tc = 0.13 with consequent photocyclization of the cis-isomer with a quantum yield of 0.23. The direct singlequantum photocyclization of the trans-isomer with a quantum yield of 0.009 is also observed. The latter observation indicates that the excited trans-isomer isomerizes without loss of excitation to the excited cis-isomer, which then undergoes cyclization, i.e., the trans-cis photoisomerization proceeds partially by adiabatic mechanism t* → c*.     

Synthesis of maresin 1 and (7S)-isomer

Maresin 1 (with the 7R carbon) and (7S)-maresin 1 were synthesized stereoselectively. The conjugated triene system was constructed by Pd-catalyzed coupling of the trans cis-dienylborane (the C10–C22 part) with the trans vinyl iodide corresponding to the C1–C9 part. The stereogenic centers at C7 and C14 were created by Ru-catalyzed asymmetric reduction of ketone and asymmetric epoxidation/kinetic resolution of the racemic alcohol, respectively.