N,N′‐Dioxide‐Magnesium Ditriflate Complex‐Catalyzed Asymmetric α‐Hydroxylation of β‐Keto Esters and β‐Keto Amides

The highly catalytic asymmetric α‐hydroxylation of 1‐tetralone‐derived β‐keto esters and β‐keto amides using tert‐butyl hydroperoxide (TBHP) as the oxidant was realized by a chiral N,N′‐dioxide‐magnesium ditriflate [Mg(OTf)₂] complex. A series of corresponding chiral α‐hydroxy dicarbonyl compounds was obtained in excellent yields (up to 99%) with excellent enantioselectivities (up to 98% ee). The products were easily transformed into useful building blocks and the precursor of daunomycin was achieved in an asymmetric catalytic way for the first time.     

Enantioselective Synthesis of cis‐4‐Formyl‐β‐lactams via Chiral N‐Heterocyclic Carbene‐Catalyzed Kinetic Resolution

An efficient synthesis of optically pure cis‐4‐formyl‐β‐lactams (up to 99% ee) by a chiral NHC‐catalyzed ring expansion reaction has been realized, featuring the ready availability of both the substrate and the catalyst, and the mild reaction conditions. The current method is also suitable for the synthesis of enantioenriched 4‐formyl‐β‐lactams and succinimides containing quaternary carbon centers.     

Synthesis and Reactions of Enantiopure Substituted Benzene cis‐Hexahydro‐1,2‐diols

Enantiopure cis‐dihydro‐1,2‐diol metabolites, obtained from toluene dioxygenase‐catalysed cis‐dihydroxylation of six monosubstituted benzene substrates, have been converted to their corresponding cis‐hexahydro‐1,2‐diol derivatives by catalytic hydrogenation via their cis‐tetrahydro‐1,2‐diol intermediates. Optimal reaction conditions for total catalytic hydrogenation of the cis‐dihydro‐1,2‐diols have been established using six heterogeneous catalysts. The relative and absolute configurations of the resulting benzene cis‐hexahydro‐1,2‐diol products have been unequivocally established by X‐ray crystallography and NMR spectroscopy. Methods have been developed to obtain enantiopure cis‐hexahydro‐1,2‐diol diastereoisomers, to desymmetrise a meso‐cis‐hexahydro‐1,2‐diol and to synthesise 2‐substituted cyclohexanols. The potential of these enantiopure cyclohexanols as chiral reagents was briefly evaluated through their application in the synthesis of two enantiomerically enriched phosphine oxides from the corresponding racemic phosphine precursors.     

(−)‐Sparteine‐Mediated Directed ortho‐Metalation of N‐Cumyl‐N‐ethylferrocenecarboxamide. Versatile Routes to Functionalized Planar Chiral Ferrocenecarboxamides,Amines, Esters and Phosphines

N‐Cumyl‐N‐ethylferrocenecarboxamide 5 provides planar chiral carboxamides 6 in high yield and % ee via (−)‐sparteine‐mediated directed ortho‐metalation. Mild decumylation affords secondary amides 7 , which serve as intermediates for a convenient and general route to the venerable Ugi planar chiral ferrocenylamines 13 and as versatile precursors for the preparation of novel chiral ferrocenes 15 and 20 . The chiral TMS‐ferrocenyl derivative 7c is used to prepare the enantiomeric (S)‐ 7f , circumventing the lack of availability of (+)‐sparteine.     

Storable and Air‐Stable Zirconium Complex‐Catalyzed Highly Enantioselective Darzens Reaction of Diazoacetamide with Aldehydes

An asymmetric Darzens reaction of aldehydes with diazo‐N,N‐dimethylacetamide ( 3 ) catalyzd by an air‐stable and storable chiral zirconium Lewis acid catalyst, which is formed from 3,3′‐diiodobinaphthol and tetrabutoxyzirconium, gives solely the cis‐glycidic amides in high yields with excellent enantioselectivity (up to 97% yield, >99% ee).     

Influence of imine‐carbon substituent in 6‐bromo‐2‐iminopyridine‐based cobalt(II) complexes on 1,3‐butadiene polymerization

6‐Bromo‐2‐iminopyridine cobalt(II) complexes bearing different imine‐carbon substituents ( Co1 – Co7 ) were synthesized and subsequently employed for 1,3‐butadiene polymerization. All the complexes were identified using Fourier transform infrared spectra and elemental analysis, and complexes Co1 and Co3 were further characterized using single‐crystal X‐ray diffraction analysis, demonstrating they adopted distorted trigonal bipyramidal and tetrahedral geometries, respectively. Activated by methylaluminoxane, these complexes exhibited high cis‐1,4 selectivity, and the activity was highly dependent on the substituent at the imine‐carbon position of the ligand. Addition of PPh₃ to the polymerization systems could enhance the catalytic activity and simultaneously switched the selectivity from cis‐1,4 to cis‐1,2 manner. On the basis of the obtained results, a plausible mechanism involving the regulation of selectivity and activity is proposed. © 2019 Society of Chemical Industry     

Highly Diastereoselective Indium‐Mediated Allenylation of N‐tert‐Butanesulfinyl Imino Ester: Efficient Synthesis of Optically Active α‐Allenylglycines

An efficient and practical asymmetric synthesis of highly enantiomerically enriched α‐allenylglycines by room temperature indium‐mediated allenylation of chiral N‐tert‐butanesulfinyl imino esters with propargylic halides is described. The synthetic utilities of the approach were demonstrated by the rapid and convenient preparation of challenging cis‐substituted proline derivatives.     

Intramolecular Photochemical Cross‐Coupling Reactions of 3‐Acyl‐2‐haloindoles and 2‐Chloropyrrole‐3‐carbaldehydes with Substituted Benzenes

Highly efficient syntheses of indolo[2,1‐a]isoquinolines, indolo[2,1‐a][2]benzazepines, pyrrolo[2,1‐a]isoquinolines and pyrrolo[1,2‐a]benzazepines in excellent yields have been achieved by the intramolecular photochemical cross‐coupling reactions of 3‐acyl‐2‐halo‐N‐(ω‐arylalkyl)indoles and 2‐chloro‐N‐(ω‐arylalkyl)pyrrole‐3‐carbaldehydes in acetone. A new heterocyclic ring system – pyrrolo[1,2‐d][1,4]benzoxazepine – has also been constructed for the first time in this work by the photocyclization of 2‐chloro‐N‐(2‐phenoxyethyl)pyrrole‐3‐carbaldehyde.     

Catalytic Asymmetric Hydrogenation of α‐Arylcyclohexanones and Total Synthesis of (−)‐α‐Lycorane

An efficient catalytic asymmetric hydrogenation of racemic α‐arylcyclohexanones with an ethylene ketal group at the 5‐position of the cyclohexane ring via dynamic kinetic resolution has been developed, giving chiral α‐arylcyclohexanols with two contiguous stereocenters with up to 99% ee and >99:1 cis/trans‐selectivity. Using this highly efficient asymmetric hydrogenation reaction as a key step, (−)‐α‐lycorane was synthesized in 19.6% overall yield over 13 steps from commercially available starting material.     

Highly Stereoselective Synthesis of Novel Multistereogenic Bis‐Bifunctional Ligands Based on [2.2]Paracyclophane‐ 4,7‐quinone,their Structure Elucidation and Application in Asymmetric Catalysis

Bis‐bifunctional cis‐4,7‐diarylsubstituted‐4,7‐dihydroxy‐4,7‐dihydro[2.2]paracyclophanes 3–6 were synthesized by a highly diastereoselective reaction of ortho‐substituted aryllithium reagents with [2.2]paracyclophane‐4,7‐quinone ( 1 ). Enantiomerically pure diols 3–5 were tested as chiral inductors in the enantioselective addition of diethylzinc to benzaldehyde (up to 93.5% ee). Acid dehydration of cis‐4,7‐di(2‐methoxyphenyl)‐4,7‐dihydroxy‐4,7‐dihydro[2.2]paracyclophane ( 3 ) results in 4,7‐dihydro‐7,8‐di(2‐methoxyphenyl)[2.2]paracyclophane‐4‐one ( 8 ) – a planar chiral cyclohexadienone of the [2.2]paracyclophane series with a para‐semiquinoid substructure. X‐Ray investigations of compounds 3, 4 and 8 were performed.     

Enantioselective Synthesis of Chiral β‐Aryloxy Alcohols by Ruthenium‐Catalyzed Ketone Hydrogenation via Dynamic Kinetic Resolution (DKR)

A highly efficient enantioselective synthesis of chiral β‐aryloxy alcohols by the {RuCl₂[(S)‐SDP][(R,R)‐DPEN]} [(S_a,R,R)‐ 1a ; SDP=7,7′‐bis(diarylphosphino)‐1,1′‐spirobiindane; DPEN=trans‐1,2‐diphenylethylenediamine] complex‐catalyzed asymmetric hydrogenation of racemic α‐aryloxydialkyl ketones via dynamic kinetic resolution (DKR) has been developed. Enantioselectivities of up to 99% ee with good to high cis/anti‐selectivities (up to>99:1) were achieved.     

Tandem enzyme‐catalysed reduction/ cis‐dihydroxylation of 2,2,2‐trifluoroace‐ tophenone: chemoenzymatic routes to new enantiopure phenol and benzylic alcohol reagents

Factors that control the competition between toluene dioxgenase‐catalysed arene cis‐dihydroxylation and dehydrogenase‐catalysed ketone reduction have been studied, using whole cells of Pseudomonas putida UV and three alkylaryl ketones. The triol metabolite, obtained from 2,2,2‐trifluoroacetophenone, has been used in the synthesis of single enantiomer chiral phenols and benzylic alcohols. Potential applications of the methylether derivatives of the chiral phenols and benzylic alcohols, as resolving agents, have been found. Copyright © 2007 Society of Chemical Industry     

Highly Efficient Catalytic Asymmetric Sulfa‐Michael Addition of Thiols to trans‐4,4,4‐Trifluorocrotonoylpyrazole

A new protocol for the efficient construction of chiral trifluoromethylated building blocks was developed via organocatalyzed sulfa‐Michael addition of thiols to the cost‐efficient trans‐trifluorocrotonamide. Introducing the pyrazole moiety is crucial to providing H‐bond acceptor sites for better activation and hence affording comparable asymmetric induction with that obtained when employing the expensive cis‐4,4,4‐trifluorocrotonate as the Michael acceptor.     

Synthesis of Chiral Amino Acid Anilides by Ligand‐Free Copper‐Catalyzed Selective N‐Arylation of Amino Acid Amides

An atom‐economic, practical and cost‐effective protocol for synthesis of chiral amino acid anilides via ligand‐free copper‐catalyzed selective C N cross coupling of chiral amino acid amides and aryl halides, hetereoaryl halides and a vinyl bromide has been developed. No racemization occurred during the C N coupling. A plausible mechanism is proposed.     

Efficient Catalytic Asymmetric Synthesis of trans‐5‐Aryl‐2‐substituted Cyclohexanones by Rhodium‐Catalyzed Conjugate Arylation of Racemic 6‐Substituted Cyclohexenones

Catalytic asymmetric conjugate arylation of racemic 6‐substituted cyclohexenones with arylboronic acids was catalyzed by 3 mol % of chiral amidophosphane‐[RhCl(C₂H₄)]₂ in a 10:1 mixture of 1,4‐dioxane and water at 70 °C to afford a nearly 1:1 mixture of trans‐ and cis‐5‐aryl‐2‐substituted cyclohexanones in high enantioselectivity, which was subsequently epimerized with sodium ethoxide in ethanol to give thermodynamically stable trans‐5‐aryl‐2‐substituted cyclohexanones with 99–97 % ee in high two‐step yields.     

Construction of Chiral 2‐Substituted Octahydroindoles from Cyclic Ketones and Nitroolefins Bearing only One α‐Substituent

A dual catalytic system has been developed following the screening of a series of chiral primary amine catalysts and chiral phosphoric acid catalysts for the Michael addition of cyclic ketones to nitroolefins bearing only one α‐substituent. The resulting γ‐nitro ketones, which contain a substituent on the carbon connected to the nitro group, were formed in excellent yields (>80%) with high levels of stereoselectivity (up to 94:6 dr and 98% ee) when the reaction was performed in benzene at 0 °C with 10 mol% of the optimal amine/phosphoric acid combination (1:1) as a catalyst. Subsequent reduction of the nitro group followed by intramolecular reductive amination could afford optically active cis‐octahydroindole analogues bearing a non‐functional substituent at their 2‐position.

     

N,N,N′,N′‐Tetramethylchloroformamidinium Chloride‐Mediated Cyclizations of β‐Oxo Amides: Facile and Divergent One‐Pot Synthesis of Substituted 2H‐Pyrans, 4H‐Pyrans and Pyridin‐2(1H)‐ones

An efficient and divergent one‐pot synthesis of substituted 2H‐pyrans, 4H‐pyrans and pyridin‐2(1H)‐ones from β‐oxo amides based on the selection of the reaction conditions is reported. Mediated by N,N,N′,N′‐tetramethylchloroformamidinium chloride, β‐oxo amides underwent intermolecular cyclizations in the presence of triethylamine at room temperature to give substituted 2H‐pyrans in high yields, which could be converted into substituted 4H‐pyrans in the presence of sodium hydroxide in ethanol at room temperature, or into substituted pyridin‐2(1 H)‐ones under reflux.     

Darstellung und Atropisomerie von 1‐(2‐Aryl)‐piperidin‐2‐onen

Preparation and Atropisomerism of 1‐(2‐Aryl)‐piperidin‐2‐ones Course and rate of the dehydrogenation of N‐tertiary piperidines dependent on their substitution in 4‐position and on the hydroxy bearing neighbor group were examined, using mercury(II)‐EDTA and the model amino alcohols 1a 1e, 3a 3f, 8a 8f and 10a 10f . The results showed that increasing size of 4‐substituents and neighbor groups too decreased the rate of reaction. The products from the 2‐substituted benzylic alcohols, the 2‐piperidones 7a 7g, 9a 9g and 11a 11g demonstrated atropisomerism. In the case of chiral neighbor groups diastereomeric mixtures were formed.     

Synthesis and Highly Stereoselective Hydrogenation of the Statin Precursor Ethyl (5S)‐5,6‐Isopropylidenedioxy‐3‐oxohexanoate

A search for the large‐scale preparation of (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoates ( 2 ) – a key intermediate in the synthesis of pharmacologially important statins – starting from (S)‐malic acid is described. The synthesis of the required initial compound methyl (3S)‐3,4‐(isopropylidenedioxy)butanoate ( 1 ) by Moriwake’s reduction of dimethyl (S)‐malate ( 3 ) has been improved. Direct 2‐C chain elongation of ester 1 using the lithium enolate of tert‐butyl acetate has been shown to be successful at a 3‐ to 5‐fold excess of the enolate. Unfortunately, the product, tert‐butyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate ( 2a ) is unstable during distillation. Ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate ( 2b ) was prepared alternatively on a multigram scale from (3S)‐3,4‐(isopropylidenedioxy)butanoic acid ( 7 ) by activation with N,N′‐carbonyldiimidazole and subsequent reaction with Mg(OOCCH₂COOEt)₂. A convenient pathway for the in situ preparation of the latter is also described. Ethyl ester ( 2b ) can be advantageously purified by distillation. The stereochemistry of the catalytic hydrogenation of β‐keto ester ( 2b ) to ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐hydrohyhexanoate (syn‐ 6 and anti‐ 6 ) has been studied using a number of homogeneous achiral and chiral Rh(I) and Ru(II) complexes with phosphine ligands. A comparison of Rh(I) and Ru(II) catalysts with (S)‐ and (R)‐BINAP as chiral ligands revealed opposite activity in dependence on the polarity of the solvent. No influence of the chiral backbone of substrate 2b on the enantioselectivity was noted. A ratio of syn‐ 6 /anti‐ 6 =2.3 was observed with an achiral (Ph₃P)₃RuCl₂ catalyst. Ru[(R)‐Tol‐BINAP]Cl₂ neutralized with one equivalent of AcONa afforded the most efficient catalytic system for the production of optically pure syn‐(5S)‐5,6‐isopropylidenedioxy‐3‐hydroxyhexanoate (syn‐ 6 ) at a preparative substrate/catalyst ratio of 1000:1.     

Step‐growth polymerization of 5‐[(9,10‐dihydro‐9,10‐ethanoanthracene‐11,12‐dicarboximido)‐3‐methylbutanoyl‐amino]isophthalic acid with aromatic diols

cis‐9,10‐dihydro‐9,10‐ethanoanthracene‐11,12‐dicarboxylic acid anhydride ( 1 ) was converted to imide acid ( 2 ) by reaction with S‐valine. Compound 2 was converted to the acid chloride ( 3 ) by reaction with thionyl chloride and then treated with 5‐aminoisophthalic acid in dry N,N‐dimethylacetamide to obtain 5‐[(9,10‐dihydro‐9,10‐ethanoanthracene‐11,12‐dicarboximido)‐3‐methylbutanoylamino]isophthalic acid ( 4 ). Direct step‐growth polymerization of this novel chiral diacid monomer 4 with a series of different diols in a system of tosyl chloride, pyridine, and N,N‐dimethylformamide was carried out. The optically active polyesters (PEs) were obtained with good yield and moderate inherent viscosity ranging from 0.23 to 0.48 dL/g. The resulting polymers were characterized with FTIR, ¹H‐NMR, and elemental analysis techniques. The prepared PEs showed good thermal stability up to 320°C as measured by thermogravimetric analysis. Specific rotation experiments demonstrated the induction of optical activity due to successful insertion of S‐valine in the structure of pendant groups. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010