Structure Elucidation of the Diagnostic Product Ion at <Emphasis Type="Italic">m/z</Emphasis> 97 Derived from Androst-4-en-3-One-Based Steroids by ESI-CID and IRMPD Spectroscopy

Structure elucidation of steroids by mass spectrometry has been of great importance to various analytical arenas and numerous studies were conducted to provide evidence for the composition and origin of (tandem) mass spectrometry-derived product ions used to characterize and identify steroidal substances. The common product ion at m/z 97 generated from androst-4-ene-3-one analogs has been subject of various studies, including stable isotope-labeling and (high resolution/high accuracy) tandem mass spectrometry, but its gas-phase structure has never been confirmed. Using high resolution/high accuracy mass spectrometry and low resolution tandem mass spectrometry, density functional theory (DFT) calculation, and infrared multiple photon dissociation (IRMPD) spectroscopy employing a free electron laser, the structure of m/z 97 derived from testosterone was assigned to protonated 3-methyl-2-cyclopenten-1-one. This ion was identified in a set of six cyclic C₆H₉O⁺ isomers as computed at the B3LYP/6-311++G(2d,2p) level of theory (protonated 3-methyl-2-cyclopenten-1-one, 2-methyl-2-cyclopenten-1-one and 2-cyclohexen-1-one). Product ions of m/z 97 obtained from MS² and MS³ experiments of protonated 3-methyl-2-cyclopenten-1-one, 2-methyl-2-cyclopenten-1-one, 2-cyclohexen-1-one, and testosterone corroborated the suggested gas-phase ion structure, which was eventually substantiated by IRMPD spectroscopy yielding a spectrum that convincingly matched the predicted counterpart. Finally, the dissociation pathway of the protonated molecule of testosterone to m/z 97 was revisited and an alternative pathway was suggested that considers the exclusion of C-10 along with the inclusion of C-5, which was experimentally demonstrated with stable isotope labeling.     

Synthesis of heterocyclic compounds related to fredericamycin A – the cyclopent[g]isoquinoline system

A synthetic route is described to compounds 9 and 10 , which resemble the cyclopent[g]isoquinoline system of the antitumor agent, Fredericamycin A. The method is based upon directed lithiation of the pyridine 6 and conjugate addition to 2-cyclopenten-1-one. Cyclization of the product 7 with base then generates the required skeleton, which can be aromatized and methylated (7 → 8 → 9).     

Synthesis of some cyclopentenones and crystal structure of 4-hydroxy-3,4-bis(4-methoxyphenyl)-5,5-dimethyl-2-cyclopenten-1-one

Abstract  

Sodium-hydroxide-catalyzed condensation of di-p-methyl- and di-p-methoxybenzil with acetone derivatives was investigated in methanol. Di- and trisubstituted products were obtained as cyclopentenones, while tetraaryl-substituted systems were isolated as cyclopentadienones. The structures of the products were identified by elemental analysis, infrared (IR), nuclear magnetic resonance (¹H NMR), and mass spectroscopy. The solid-state structure of 4-hydroxy-3,4-bis(4-methoxyphenyl)-5,5-dimethyl-2-cyclopenten-1-one was further studied by single-crystal X-ray diffraction analysis. The title compound crystallizes in an orthorhombic space group and intermolecular O–H···O and C–H···O hydrogen bonds stabilize the crystal lattice.     

Untersuchungen über Synthesewege zu 2-Äthynyl-2-cyclopenten-1-onen

Synthetic approaches to 2-ethynyl-2-cyclopenten-1-ones (A) by dehydratation of the readily obtainable 2-(1-alkynyl)-2-hydroxy-cyclopentanones1 a and1 b were investigated. The synthesis of 2-(3,3,3-triphenylpropynyl)-2-cyclopenten-1-one (6) was achieved by reaction of 1-(3,3,3-triphenylpropynyl)-6-oxabicyclo[3.1.0]hexane (3 b) with HCl and CrO₃-oxidation of the resulting 2-(3,3,3-triphenylpropynyl)-2-cyclopenten-1-ol (4).     

Chiral phosphorus ligands for the asymmetric conjugate addition of organocopper reagents

The asymmetric conjugate addition of medium order alkyl cuprate reagents. R₅Cu₃Li₂, to 2-cyclohexen-1-one. 2-cyclopenten-1-one and 2-cyctohepten-1-one, with the help of phosphorus ligand B^*, is described. 3-Alkyl substituted cyclohexanones are obtained in essentially optically pure form. The same chiral ligand, associated with CuI, in catalylic amount (10%), allows the asymmetric conjugate addition of Et₂Zn to 2-cyclohexen-1-one.     

An Efficient Route to 2-(Formylmethyl)-Cyclopenten-3-one and Its 1-methyl-Congener

We describe a five-step synthesis of 2-(formylmethyl) - cyclopenten-3-one (1a) and its 1-methyl congener (1b) from 6-methylhept-5-ene-2-one by way of the respective 2-(3-methylbut-2-enyl)-cyclopenten-3-ones (5) and selective ozonolysis of these intermediates.     

Novel vanadyl complexes with 2-hydroxy-3-methyl-2-cyclopenten-1-one

Two examples of novel vanadyl complexes of 2-hydroxy-3-methyl-2-cyclopenten-1-one, Hmcp, with 1:2 stoichiometry have been characterised by elemental analysis, i.r. and optical spectral studies. [VOCl₂(H₂O)(Hmcp)₂] (1) contains neutral Hmcp coordinated to vanadium through a carbonyl oxygen and both molecules are trans to each other. [VO(mcp)₂H₂O] (2) contains the mono-anionic form of Hmcp. Both complexes have distorted octahedral geometry.     

Vinyltriphenylphosphonium Salt Mediated One-Pot Stereoselective Synthesis of Dialkyl ( E )-2-(2-methyl-5-oxo-1-cyclopentenyl)-2-butenedioates

Protonation of the highly reactive 1:1 intermediates produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates by 2-hydroxy-3-methyl-2-cyclopenten-1-one leads to vinyltriphenylphosphonium salts, which undergo an intramolecular Wittig reaction to produce the corresponding cyclobutene derivatives. The cyclobutene derivatives are not isolable and undergo electrocyclic ring-opening reactions in CH 2 Cl 2 at room temperature to produce dialkyl ( E )-2-(2-methyl-5-oxo-1-cyclopentenyl)-2-butenedioates in moderate yields.     

High Pressure Lewis-Acid Catalyzed Diels-Alder Reactions of 3-Methyl-2-cyclopenten-1-one. A New Construction of Angularly Methylated Hydrindanones

The Diels-Alder reactions of 3-methyl-2-cyclopenten-1-one with simple acyclic dienes under high pressure in combination with EtAlCl₂ are described. Angularly methylated hydrindanones were isolated in reasonably to good yields. Structure analysis of the reaction products by NMR spectroscopy is presented.     

Synthesis and stereochemistry of the (9S,13S,14S)-3-hydroxy-17-methylmorphinan-10-ols

O-Demethylation of (9S,13S,14S)-3-methoxy-17-methylmorphinan-10-one ( 2 ) to (9S,13S,14S)-3-hydroxy-17-methylmorphinan-10-one ( 3 ) and reduction of 3 to 10α- and 10β-hydroxylated morphinans 4 and 5 , are described. The stereochemistry of these epimeric alcohols was established on the bases of ¹H nmr data.     

An environmentally benign protocol: catalyst-free Michael addition of aromatic amines to α,β-unsaturated ketones in glycerol

Glycerol was used as a reaction medium as well as promoter for aza-Michael addition of aromatic amines to electronic deficient α,β-unsaturated ketones. Various aromatic amines can react smoothly with chalcone, 2-cyclohexen-1-one, 2-cyclopenten-1-one, and ethyl vinyl ketone to achieve good to excellent yields in the absence of any catalyst.     

An efficient constructive method for a tricyclic system: an important intermediate for the synthesis of tricycloclavulone

The tricyclic ring system of tricycloclavulone was synthesized from 2-methoxycarbonyl-2-cyclopenten-1-one (2). Key reactions include Lewis acid-catalyzed [2+2]-cycloaddition of α,β-unsaturated ester 2 with thioacetylene derivatives and construction of the A-ring by using the Grubbs catalyst.     

Catalytic,asymmetric aza-Baylis–Hillman reaction of N-sulfonated imines with 2-cyclohexen-1-one and 2-cyclopenten-1-one in the presence of a chiral phosphine Lewis base

In the aza-Baylis–Hillman reaction of N-sulfonated imines with 2-cyclohexen-1-one or 2-cyclopenten-1-one, we found that by using (R)-2′-dimethylphosphanyl-[1,1′]binaphthalenyl-2-ol LB1 as a chiral phosphine Lewis base, the corresponding Baylis–Hillman adducts 2 or 3 can be obtained in good yields and moderate enantiomeric excess. The structure of this chiral phosphine Lewis base on chiral induction in this reaction has also been discussed.     

Enantioselective formal synthesis of (+)-precapnelladiene by chiral copper-catalyzed asymmetric [2+2]-cycloaddition reaction

Enantioselective short formal synthesis of (+)-precapnelladiene (1) was achieved from a bicyclo[3.2.0]heptane derivative, which was prepared enantioselectively by chiral copper-catalyzed [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one with phenylthioacetylene developed by us.     

二氢新茉莉酮酸甲酯和二氢茉莉铜酸甲酯的合成

本文报道了二氢茉莉酮酸甲酯(1)和二氢新茉莉酮酸甲酯(2)的新合成路线,以丙二酸二乙酯为原料,依次与溴代戊烷和烯丙基溴进行烷基化反应,得到α-戊基-α-烯丙基-丙二酸二乙酯(5),5经过水解、脱羧得到γ-烯酸3.酰氯化合物6进行Friendel-Crafts反应得到2-戊基-环戊-4-烯-1-酮(7),7通过Michael加成、水解、脱羧和酯化,得到2,总产率为24.4%.7可以异构化为2-戊基-环戊-2-烯-1-酮(9),9用通常的方法合成了1.1和2可以明显地从核磁共振谱、红外光谱和气相色谱识别。     

Asymmetric 1,4-addition of β-keto esters to cyclic enones catalyzed by Ru amido complexes

Well-defined Ru amido complexes effected asymmetric Michael addition of β-keto esters to 2-cyclopenten-1-one to give quantitatively the corresponding Michael adducts with excellent ee although with a 1:1 diastereomer ratio. The stereochemical outcome of the reaction was significantly influenced by the structures of the catalysts and the structures of the β-keto esters; the ee value reaching up to 97%.     

Organometallic compounds in organic synthesis: reactions of some tricarbonylcyclohexadienyliumiron complexes with 1,2-bis(trimethylsiloxy)-1-cyclopentene. A novel route to 2-(substituted)-2-cyclopenten-1-ones.

1,2-Bis(trimethylsiloxy)-1-cyclopentene reacts with a range of tricarbonylcyclohexadienyliumiron cations to give initially siloxy acyloins, treatment of which with MeOH-HCl gives the 2-(substituted)-2-cyclopenten-1-one in good yields (56–78%).     

Asymmetric Morita-Baylis-Hillman reaction of arylaldehydes with 2-cyclohexen-1-one catalyzed by chiral bis(thio)urea and DABCO

Novel bis(thio)urea organocatalysts were synthesized from axially chiral (R)-(-)-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl-2,2'-diamine (H8-BINAM), and their catalytic abilities have been examined in the Morita-Baylis-Hillman reaction of 2-cyclohexen-1-one or 2-cyclopenten-1-one with a wide range of aromatic aldehydes in combination with DABCO. The best result was achieved in the reaction of 3-fluorobenzaldehyde with 2-cyclohexen-1-one to give the desired Morita-Baylis-Hillman product in 79% yield and 88% ee.     

Diels–Alder reactions and transformations of 2-cyclopenten-1-one with a chiral anthracene template

Excellent regio- and diastereoselectivity were achieved in the microwave assisted Diels–Alder reaction between (S)-9-(1-methoxyethyl) anthracene and 2-cyclopenten-1-one. The addition of Grignard reagents to the ketone cycloadduct gave poor levels of diastereoselectivity, however, the reduction was significantly more stereoselective. Flash vacuum pyrolysis of the reduced material furnished the corresponding allylic alcohol in good yield and ee.     

Theoretical modelling of the epoxidation of vinylallenes to give cyclopentenones

Epoxidation of vinylallenes (1,2,4-pentatrienes) can lead to cyclopent-2-enones. Various experimental results suggest that these reactions are concerted and that vinylallene oxides undergo a concerted and thermal ring-closing reaction to give cyclopentenones. In 1977, this view has been supported by the epoxidation of a non-racemic 4-methyl-2,3,5-hexatriene to give a non-racemic 2,5-dimethyl-2-cyclopenten-1-one. Indeed, for the cyclization of (3E)-4-methyl-2,3-epoxy-2,3,5-hexatriene or (4E)-4-methyl-3,4-epoxy-2,3,5-hexatriene into 2,5-dimethyl-2-cyclopenten-1-one, a transition structure for the concerted rearrangement was located, and IRC calculations showed it linked together. The activation barrier predicted at the B3LYP/6-311++G(3df,3pd)//B3LYP/6-31G(d) level of theory is 80.9 or 124.2 kJ mol⁻¹, respectively and the reaction is exothermic by 127.2 or 89.2 kJ mol⁻¹, respectively.