Les dimethyl-2ξ, 17α,δ9 et δ9,11 nor-19-testosterones. Conformation du cycle a et equilibres en solution

The preparation of 2α- and 2β-isomers of the 2,17-dimethyl-17β-hydroxy estra-4,9 diene-3-ones, 4 and the 2,17-dimethyl-17β-hydroxy estra-4,9,11 triene-3-ones, 21, is described and the configuration at C₂ established by chemical means. CD spectra show that these compounds exist in solution as an equilibrium mixture of two conformers, the proportion depending on the configuration of the methyl group on carbon 2. It appears that ring A of the 2β isomers is in a preferred “inverted half-chair” conformation while the “normal half-chair” conformation is favoured with the methyl group in the 2α-configuration. In alkaline medium the methyl group at C₂ of the dienones 4 and the trienones 21 is partially isomerised and at equilibrium the resulting CD spectra are identical to those of the unsubstituted dienone 1 and trienone 15. An explanation of this phenomenon is given.     

Regioselective synthesis of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones based on [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-silyloxy-2-en-1-ones

A variety of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones were prepared by formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-(silyloxy)alk-2-en-1-ones.     

Reduction of 6/7-substituted 3-phenyltrop-3-en-2-ones: stereoselectivity and conformational analysis of the products

Reduction of 6/7-carboethoxy-3-phenyltrop-3-en-2-ones with H₂/Pd/C and NaBH₄ was studied in order to find a stereoselective route to the corresponding 3-phenyltropan-2-ones and 2α/2β-hydroxy-3-phenyltropanes. The 6/7-exo-carboethoxy-3-phenyltrop-3-en-2-ones were selectively reduced by Pd/C to 3β-phenyltropan-2-ones and 2α-hydroxy-3β-phenyltropanes. The corresponding 2β-hydroxy-3β-phenyl analogues were synthesized using NaBH₄, with a yield of 40%. Reduction of 6-endo-carboethoxy-3-phenyltrop-3-en-2-one yielded several products. The corresponding 7-endo-substituted analogue was selectively reduced with both Pd/C and NaBH₄ to 7-endo-carboethoxy-3β-phenyltropin-2-one. Analysis of stereochemically important ¹H NMR spectroscopy parameters was performed for all the products and used for conformational analysis in solution. X-ray analysis was performed for selected compounds.     

(l)-Proline-catalysed novel tandem reactions of 1-substituted piperidin-4-ones with (E)-4-arylbut-3-en-2-ones: N-substituent mediated product selectivity and synthesis of novel nitrogen heterocycles

(l)-Proline-catalysed reaction of 1-alkyl/aralkylpiperidin-4-ones with (E)-4-arylbut-3-en-2-ones furnishes novel isoquinoline derivatives, with two or three rings, in good yields via tandem Robinson annulation-Michael addition(s) sequences, while the reaction of 1-arylpiperidin-4-ones with (E)-4-arylbut-3-en-2-ones affords 3-azabicyclo[3.3.1]nonan-9-ones via a tandem Michael addition-aldol reaction sequence.     

On the conformation of 8-substituted bicyclo [3.2.1] oct-6-en-3-ones

A series of 8-substituted bicyclo [3.2.1] oct-6-en-3-ones (of type i) possessing various R₁ and R₂ groups were prepared and characterized. The conformations of the possible isomers of 1-4 were assigned according to the following three methods: (a) NMR spectrum, (b) time averaged precise metal ion location within the Eu (dpm)₃-carbonylic compound complex, (c) UV spectra. Comparison of the chair and boat conformers by UV spectra showed that interactions between the double bonds and the carbonyl occurred in both cases, although to different extents, the ε being dependent on R₁ and R₂. The fore-mentioned interaction exists even in both series of the C₆C₇ dihydro derivatives.     

Stereoselective reduction of chiral trans-3-acetyl-4-alkylpyrrolidin-2-ones

A number of trans-3-acetyl-4-alkylpyrrolidin-2-ones 8a–d and 11a,b were prepared and reduction of the keto group, carried out with KBH₄ in CH₃OH, led mainly to 3-hydroxyethylpyrrolidin-2-ones 13a–d and 19a,b with high stereoselection. Configuration of the newly formed stereogenic centre on the hydroxyethyl chain was assigned by ¹H NMR data supported by molecular mechanic calculations and eventually confirmed by X-ray diffraction analysis of p-iodobenzoate derivative 15.     

One-pot synthesis of quinazolin-4(3H)-ones and fused quinazolinones by a palladium-catalyzed domino process

An efficient one-pot synthesis of quinazolin-4(3H)-ones, benzoimidazo[2,1-b]quinazolin-12(6H)-ones and imidazo[2,1-b]quinazolin-5(1H)-ones via a palladium-catalyzed domino process has been developed. The Pd-catalyzed reactions of 2-azidobenzamides 1 with isocyanides 2 produced quinazolin-4(3H)-ones 4 at room temperature by a domino Pd-catalyzed cross-coupling/carbodiimide-mediated cyclization. However, as 2-azido-N-(2-bromophenyl)benzamides 1 were used under heating condition in the presence of Cs₂CO₃, the benzoimidazo[2,1-b]quinazolin-12(6H)-ones 5 were directly obtained by twice Pd-catalyzed domino cyclization. A domino reogioselective 5-exo-dig intramolecular cyclization reaction of alkynyl-containing azides 6 with isocyanides 2 generated imidazo[2,1-b]quinazolin-5(1H)-ones 9 in 74–93% yields in the presence of catalyst Pd(PPh₃)₄ and K₂CO₃.     

Rearrangement products of some 1R,4R-2-arylidene-p-menthan-3-ones in acidic media, their structures, and conformational analysis

1R,4R-2-(4-Phenylbenzylidene)-p-menthan-3-one in acidic media undergoes rearrangement with migration of the exocyclic double bond to the cyclohexane ring to form three 2-(4-phenylbenzyl) derivatives ofp-menthen-3-ones. The reaction products differ in the location of the endocyclic double bond (Δ¹ or Δ⁴) and in the configuration of the new chiral C(2) center in the resultingp-menth-4-en-3-ones. The configurations of the 1R,2R- and 1R,2S-2-(4-phenylbenzyl)-p-menth-4-en-3-ones were established based on analysis of their¹H NMR spectra in combination with calculations by molecular mechanics. The molecular conformations of these compounds as well as of some racemic 2-benzyl-p-menth-1-en-3-one derivatives were studied.     

Conformational analysis of 2,4,5-trimethyl-1,3,2-dioxaborinane individual stereoisomers

The study of the conformational isomerization of cis- and trans-isomers of 2,4,5-trimethyl-1,3-dioxaborinane I by means of RHF//STO-3G, 3-21G and 6-31G(d) quantumchemical methods led to the conclusion that its route includes equilibrium between sofa conformers with a different steric orientation of substituents at the C-4 and C-5 ring atoms. These conformers are interconverted through the maxima, the conformations of equatorial and axial 2,5-twist-forms. A comparison between experimental ¹H NMR and theoretical vicinal spin-spin coupling constants was used to determine the quantitative conformational composition of stereoisomers and a value of ΔG ⁰ for conformational equilibrium.     

8-Azabicyclo[3.2.1]oct-3-en-2-ones via asymmetric 1,3-dipolar cycloaddition of a homochiral 3-oxidopyridinium betaine

8-Azabicyclo[3.2.1]oct-3-en-2-ones were prepared by asymmetric 1,3-dipolar cycloadditions of homochiral pyridinium betaine 4. Excellent diastereofacial selectivity was achieved for the major 6-exo cycloadducts. The absolute stereochemistry of cycloadduct 7 was confirmed by a single-crystal X-ray diffraction study.     

A method for synthesis of bicyclo[3.3.0]oct-1-en-3-ones from cyclobutanones with one-carbon ring expansion and its application to a formal synthesis of racemic 1-desoxyhypnophilin

A method for synthesis of 2-cyanobicyclo[3.3.0]oct-1-en-3-ones and 2-substituted bicyclo[3.3.0]oct-1-en-3-ones was developed by assembly of three components, cyclobutanones, chloromethyl p-tolyl sulfoxide, and nitriles, with one-carbon ring expansion of the cyclobutane ring. As an application of this method, a formal synthesis of 1-desoxyhypnophilin in racemic form was performed starting from 3,3-di(phenylthiomethyl)cyclobutanone.     

Stereochemistry and 13C NMR investigation of 9-halotetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones

It was shown that the halogen atom occupies the quasi-axial position in the predominant conformer of the 9-halo derivatives of tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones. When R³ = Me, the conformational equilibrium is determined by the latter substituent which is always quasi-axial. The effects of the methyl group and the halogen atoms on the ¹³C chemical shifts (SCS values) were used for the identification of cis and trans isomers. Interesting non additivity of substituent effects was found in derivatives bearing quasi-axial substituents at C-6 and C-9: and this was caused by the ring flattening.     

1H NMR spectra and conformational analysis of some 1,4-dithiepan-6-ones

¹H NMR Parameters are reported for five 1,4-dithiepan-6-ones. 1,4-Dithiepan-6-one 1-oxide exists in solution as an equilibrium involving two different twist-chair conformations, which contrasts with its conformational behaviour in the solid state. Twist-chair conformers are also adopted by other members of the series, the favoured form varying with ring substitution. The S?O bond in 1,4-dithiepan-6-one 1-oxide and in its 5,5-dimethyl analogue exhibit a preference for the pseudoaxial site.     

Microwave-assisted synthesis of 1-{2-[(1-benzyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)methoxy]phenyl}-3-(3-aryl-1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)prop-2-en-1-ones and their antimicrobial activity

A series of new (E)-1-{2-[(1-benzyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones (3a–3i) has been synthesized via copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition reaction (CuAAC) of benzyl azide with substituted (E)-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-1-[2-(prop-2-ynyloxy)phenyl]prop-2-en-1-ones (2a–2i). The synthesized compounds have been characterized by their IR, ^lH, ¹³C NMR spectra, and mass spectroscopy data. All the compounds have been screened for antimicrobial activity.     

A facile synthesis and thio-Claisen rearrangement of 3-aryl-2-phenyl-5-prop-2-ynylsulfanyl-3H-pyrimidin-4-ones: regioselective transformation to thieno[3,2-d]pyrimidin-4-ones

The synthesis and transformation of previously unknown 3-aryl-2-phenyl-5-prop-2-ynylsulfanyl-3H-pyrimidin-4-ones 3a-e to novel thieno[3,2-d]pyrimidin-4-ones 4a-e are reported.     

Free-radical cyclization of enantiomerically enriched 2-p-tolylthio derivatives of 2-allylcyclohexanones with Mn(III): asymmetric synthesis of bridged bicyclic ketones and thiochroman-3-ones

Mn(III)-based oxidative intramolecular cyclization of enantiomerically enriched 2-allyl-2-(p-tolylsulfonyl)-cyclohexanone 4 and 2-allyl-2-(p-tolylsulfenyl)cyclohexanone 9 are reported. The observed chemoselectivity (reaction on the allylic double bond yielding bridged bicyclic ketones vs. reaction on the aromatic ring of the p-tolyl group affording thiochroman-3-ones) depends on the sulfur function (sulfone or thioether, respectively), which determines the electronic density of the p-tolyl ring and the conformational preferences of the starting compounds. The nature of the substituent at C-2 is related to the endo/exo selectivity of the cyclization as well as the regioselectivity in the formation of the enones.     

Synthesis of syn- and anti-tricyclo [4.1.0.02,4] heptan-5-ones and related compounds

A convenient entry to both title compounds 1 and 2, as well as to cis- and trans-4-iodomethyl-bicyclo [3.1.0]-hexan-2-ones 3and 4 and to 4-methyl-bicyclo [3.1.0]-hex-3-en-2-one 5 involving base-promoted reactions of cis- and -trans-3,4-diiodomethylcyclopentanones 6 and 7 is reported, and the behaviour of 6 and 7 towards different bases. bfv40bp4761b     

A facile synthesis of novel 3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones using microwave heating

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones (7a–w) have been synthesized by the Knoevenagel condensation reaction of 3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones (3a–d) with suitably substituted 2-(1H-indol-3-yl)2-oxoacetaldehydes (6a–g) under microwave conditions. The thioxothiazolidin-4-ones were prepared from the corresponding aryl/alkyl amines (1a–d) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a–g) were synthesized from the corresponding acid chlorides (5a–g) using HsnBu₃.     

Transition-metal-free insertion of benzyl bromides into 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde: One-pot switchable syntheses of benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones and 3-arylquinolin-4-ones mediated by base

A transition-metal-free insertion of benzyl group between aldehyde and imidazole of 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde was achieved for the first time. Two diverse sets of quinolin-4-one derivatives: benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones (2) and 3-arylquinolin-4-ones (3) were synthesized based on identical starting materials 2-(1H-benzo[d]imidazol-1-yl)benzaldehydes (1) and benzyl bromides. In the preparations, two key intermediates I and II were involved and might be synthesized in situ through the reaction of an intra-Breslow intermediate with benzyl bromide via an enol attack in the presence of base or a NHC-based enamine attack in the absence of base, respectively, in which the intra-Breslow intermediate might function as a nucleophilic reagent by following two novel different pathways.     

Substitution at C-4 in 3,5-disubstituted 4H-1,2,6-thiadiazin-4-ones

3,5-Diaryl-4H-1,2,6-thiadiazin-4-ones react with NaBH₄ to give the 3,5-diaryl-4H-1,2,6-thiadiazin-4-ols and with MeLi to give 4-methyl-3,5-diaryl-4H-1,2,6-thiadiazin-4-ols. The latter dehydrate with p-toluenesulfonic acid to give (3,5-diarylthiadiazin-4-ylidene)methanes. (3,5-Diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methane 15 suffers mono bromination with NBS to give bromo(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methane 17. Dichloro- and dibromo(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methanes 18 and 19 are formed directly from the 3,5-diphenylthiadiazin-4-one 9 via the Appel reaction using Ph₃P and CCl₄ or CBr₄, respectively. 3,5-Diarylthiadiazin-4-ones treated with P₂S₅ give 3,5-diarylthiadiazine-4-thiones that react with tetracyanoethylene oxide to give the (thiadiazin-4-ylidene)malononitriles. Finally, the 3,5-diphenylthiadiazine-4-thione 20 reacts with ethyl diazoacetate to give ethyl 2-(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)acetate 26. The above reactions show that a variety of substitutions at C-4 of 3,5-diaryl substituted 1,2,6-thiadiazin-4-ones can be achieved, which extends the potential applications of this heterocycle. All compounds are fully characterized and a brief comparison of their spectroscopic properties is given.