[3]Ferrocenophanes with a tetramethyldisiloxane bridge: Synthesis and molecular structure

Summary 6,6,8,8-Tetramethyl-7-oxa-6,8-disila[3]ferrocenophane2 was obtained from the di(alkoxysilyl) ferrocene (H₄C₅SiMe₂OR)₂Fe (R=CH₂CH₂OCH₂CH₂OCH₂CH₂OMe) by hydrolysis and subsequent intramolecular disiloxane formation. 2,2,3,3,4,4,5,5,6,6,8,8-Dodecamethyl-7-oxa-6,8-disila-[3]ferrocenophane3 was formed by air oxidation of 2,23,3,4,4,5,5,6,6,7,7-dodecamethyl-6,7-disila[2]ferrocenophane. The crystal structures of both compounds were determined by single-crystal X-ray diffraction (2:a=8.5330(10),b=15.610(3),c=18.774(5)Å, =70.68(2), =77.94(2), =75.150(10)°,V=2259.8(8)ų,Z=6, space group P ,R=0.045,R _w =0.044;3:a=12.388(3),b=9.924(3),c=19.136(10)Å, =105.11(3)°,V=2271.2(15)ų,Z=4, space group P2₁/c,R=0.076,R _w =0.060). Owing to the flexibility of the disiloxane bridge,2 and3 are unstrained molecules.

---

[3]Ferrocenophane mit Tetramethyldisiloxan-Brücke: Synthese und Molekülstruktur

Zusammenfassung 6,6,8,8-Tetramethyl-7-oxa-6,8-disila[3]-ferrocenophan2 entsteht aus dem Di(alkoxysilyl)ferrocen (H₄C₅SiMe₂OR)₂Fe (R=CH₂CH₂OCH₂CH₂OCH₂CH₂OMe) durch Hydrolyse und anschließende intramolekulare Disiloxan-Bildung. 2,2,3,3,4,4,5,5,6,6,8,8-Dodecamethyl-7-oxa-6,8-disila[3]ferrocenophan3 wurde durch Luftoxidation von 2,2,3,3,4,4,5,5,6,6,7,7-Dodecamethyl-6,7-disila[2]ferrocenophan erhaeten. Die Kristallstrukturen beider Verbindungen wurden durch Einkristall-Röntgenstrukturanalyse bestimmt (2:a=8.5330(10),b=15.610(3),c=18.774(5)Å, =70.68(2), =77.94(2), =75.150(10)°,V=2259.8(8)ų,Z=6, Raumgruppe P ,R=0.045,R _w =0.044;3:a=12.388(3),b=9.924(3),c=19.136(10)Å, =105.11(3)°,V=2271.2(15)ų,Z=4, Raumgruppe P2₁/c,R=0.076,R _w =0.060). Wegen der Flexibilität der Disiloxan-Brücke sind2 und3 ungespannte Moleküle.

     

Rapid identification of enantioselective ketone reductions using targeted microbial libraries

A collection of about 300 microbes was surveyed for the ability to generate chiral secondary alcohols by enantioselective reduction of a series of alkyl aryl ketones. Microbial cultures demonstrating utility in reducing model ketones were arrayed in multi-well plates and used to rapidly identify specific organisms capable of producing chiral alcohols used as intermediates in the synthesis of several drug candidates. Approximately 60 cultures were shown to selectively reduce various ketones providing both the R and S enantiomers of the corresponding alcohols in 92-99% ee with yields up to 95% at 1-4 g/L. An alternative approach to chiral alcohols based on selective microbial oxidation of racemic alcohols is also reported. This study provides a useful reference for generating chiral alcohols by selective microbial bioconversion.     

Enantioselective Brønsted base catalyzed [4+2] cycloaddition using novel amino-substituted tetraphenylene derivatives

This paper is concerned with the syntheses of 1,8,9,16-tetrahydroxytetraphenylene derivatives and their applications as Brønsted base organocatalysts for [4+2] cycloaddition between anthrone and maleimides. The structural modifications of the catalysts and their related catalytic properties are described and discussed in details.     

Structure and properties of protonated N-alkyl-2-aza[3]ferrocenophanes

Protonation of N-alkyl-2-aza[3]ferrocenophanes by HCl and NH₄PF₆ affords hexafluorophosphate salts having a trialkylammonium group. Structures of the protonated and unprotonated N-(p-methylbezyl)-2-aza[3]ferrocenophanes were determined by X-ray crystallography. Variable temperature ¹³C{¹H} NMR spectra of the N-protonated N-hexyl-2-aza[3]ferrocenophane revealed inversion of the nitrogen of the 2-aza[3]ferrocenophane on the NMR time scale probably via partial deprotonation of the nitrogen atom. Cyclic voltammograms of the N-protonated compounds exhibited reversible redox peaks at higher potentials than those of the corresponding neutral ferrocenophanes.     

Enantioselective synthesis of bicylco[3.2.1]octan-8-ones using a tandem Michael-Henry reaction

Bicyclo[3.2.1]octan-8-ones have been prepared from a tandem Michael-Henry reaction between cyclohexane-1,2-diones and nitroalkenes using a quinine-derived thiourea as the catalyst. Although four stereogenic centers were created during the reaction, only two diastereomers were obtained in good diastereoselectivity and high enantioselectivity (92-99% ee). When 3-methylcyclohexane-1,2-dione (R¹=Me) was used as the substrate, only the regioisomeric product of the corresponding thermodynamic enolate was obtained.     

Enantioselective reduction of acetophenone analogues using carrot and celeriac enzymes system

<正>The enantioselective reduction of acetophenone analogues catalyzed by carrot and celeriac was performed in moderate conversions and excellent enantiomeric excesses.The steric factors and electronic effects of the substituents at the aromatic ring were found to significantly affect the efficiency of the enantioselective reduction of acetophenone analogues,while they had a little effect on the enantioselectivity of acetophenone analogues reduction.It was also found that the conversions of acetophenone analogues reduction at 33℃by means of both biocatalysts were three times as great as those at room temperature.     

Comparative toxicity of [3]ferrocenophane and ferrocene moieties on breast cancer cells

Recent results suggest that [3]ferrocenophane may be an interesting motif in the development of cytotoxic anti-cancer agents. We here report the synthesis of three such compounds based on the 1-[(p-R-phenyl)-phenyl-methylidenyl)]-[3]ferrocenophane skeleton with R = OH, NH₂ and NHC(O)CH₃ substitution on one of the phenyl rings. Cytotoxicity studies show that these compounds are up to four times more powerful against hormone-independent breast cancer cells than their corresponding ferrocene analogs.     

Unusual demetalation of iron from [2]ferrocenophane skeleton of di-nuclear ferracycle carbonyl complex

Photolysis of a hexane solution containing 1,1′- bis (trimethylsilylethynyl)ferrocene ( 1 ) and Fe (CO)₅, under argon at 0 °C led to the formation of dinuclear complexes [Fe (CO)₂{η²:η² – C (SiMe₃) = C(C₅H₄)FeC(C₅H₄) = C (SiMe₃)Fe (CO)₃}–μ–CO] ( 2 ) and [Fe (CO)₂{η²:η²–C (SiMe₃) = C(C₅H₅)–C(C₅H₅) = C (SiMe₃)Fe (CO)₃}–μ–CO] ( 3 ). DFT calculations support the experimentally observed demetalation of ferrocene unit of 2 to 3 in presence of water. These compounds were comprehensively characterized by IR and ¹H and ¹³C NMR spectroscopy and crystallographically ( 1 and 3 ).     

Development of a convenient new synthetic route to [3]ferrocenophanones

[3]Ferrocenophanone rac-8 was prepared by several non-Friedel-Crafts pathways starting from a Mannich-type coupling of 1,1'-diacetylferrocene followed by catalytic hydrogenation. Hydride abstraction from the resulting alpha-dimethylamino[3]ferrocenophane rac-14 with B(C6F5)3 followed by hydrolysis gave the ketone rac-8. Several variants of the Sommelet reaction, using ethylglyoxylate, formaldehyde or hexamethylenetetramine (urotropine) as the "oxidizing" reagent gave the alpha-[3]ferrocenophanone 8 in good to excellent yield. Some variants of these reactions were also used for the preparation of the pure enantiomer (R)-8. The electrochemical behaviour of 8 has been investigated and compared with related derivatives.     

Enantioselective Synthesis of Naproxen

The optically active naproxen was synthesized in good chemical yield and high optical purity starting from a chiral α-ketoalcohol which was prepared from enzymatic resolution of the corresponding racemic acetate using lipase as a catalyst.     

Enantioselective synthesis of (+)-anatoxin-a via enyne metathesis

A concise synthesis of the potent nAChR agonist (+)-anatoxin-a (1) has been completed by a series of nine chemical operations and in 27% overall yield from commercially available d-methyl pyroglutamate (12). The strategy featured the application of a new protocol for the diastereoselective synthesis of cis-2,5-disubstituted pyrrolidines bearing unsaturated side chains and an intramolecular enyne metathesis to provide the bridged bicyclic framework of 1. Thus, d-methyl pyroglutamate (12) was converted in five steps to 32, which underwent facile enyne metathesis to deliver the bicyclic diene 33. Selective oxidative cleavage of the less substituted carbon-carbon double bond in 33 followed by deprotection furnished (+)-anatoxin-a (1).     

Enantioselective reduction of 2-substituted tetrahydropyran-4-ones using Daucus carota plant cells

Enzymatic reduction of 2-substituted tetrahydropyran-4-ones with Daucus carota, plant cells as biocatalyst occurred in water under extremely mild and environmentally benign conditions giving a 1:1 mixture of diastereoselectively (2R,4S)- and (2S,4S)-2-aryl- or 2-alkyl-tetrahydropyranols in high yields.     

Enantioselective Synthesis of Herbarumin III by Using a Chelation‐Controlled Reduction

The total synthesis of herbarumin III ( 1 ) was achieved via an alkynide ion addition onto a chiral aldehyde and LiAlH₄/LiI reduction as key steps (Scheme 2).     

Synthesis of the first 1,3-disubstituted 1,3-butadienyl heteroannular bridged [4]ferrocenophane

An unusual heteroannular cyclization of methyl 4-(((1′-(trimethylsilyl)ethynyl)ferrocenyl)ethynyl)benzoate (11) under the basic desilylation condition yielded 1,1′-(l-methoxy-3-(4′-(methoxycarbonyl)phenyl)-1,3-butadienylene)ferrocene (7), the first reported 1,3-disubstituted 1,3-butadienyl heteroannular bridged [4]ferrocenophane. Compound 7 has been characterized by elemental analysis, IR spectra, ¹H NMR spectroscopy and X-ray diffraction analysis. The electrochemical behavior has been investigated by cyclic voltammetry. The DFT calculation results of 7 are also reported.     

A new series of chiral catalysts for the enantioselective borane reduction of ketones

A new series of 1,3,2-oxazaborolidine catalysts substituted in position 4 by the (CH3)3C(CH2)n group (n=2, 3, 4, 5) were synthesized and applied to the borane reduction of prochi-ral ketones. The relationship between catalyst structure and enantioselectivity was discussed.     

Synthesis and Reaction of Some Indenopyridine and Thieno[2,3-b]Indeno[2,1-e]Pyridine Derivatives

Synthesis of indenopyridine-2-thione derivatives 6a-e via reaction of compound 1 with thioamides 2a-e in good yields. Several thieno[2,3-b]indeno[2,1-e]pyridine 9a-e have been synthesized. Some of them was used as a key intermediate in synthesis of 10-12. On the other hand, compound 1 reacted with various reagents to yield 16, 19, 21-24.     

Enantioselective fluorescent sensor for amino acid derivatives based on BINOL bearing hexahydropyrrolo[1,2-c]imidazol-1-one units

A chiral fluorescent sensor (Ra,S,l)-3 incorporating (R)-BINOL and l-prolinamide is found efficient in enantioselective recognition of N-Cbz-protected phenylglycine. It is observed that one enantiomer of N-Cbz-protected phenylglycine can obviously increase the fluorescence intensity of (Ra,S,l)-3, while the other enantiomer does not cause much fluorescence enhancement. Such highly enantioselective response makes the sensor (Ra,S,l)-3 useful for the enantioselective fluorescence recognition of other N-Cbz-protected amino acids.     

Syntheses and structural characterization of some mono- and di-p-nitrophenyl[3]ferrocenophanes: X-ray structure of [3]ferrocenophane, 3-p-nitrophenyl[3]ferrocenophane, and 3,4′-bis-(p-nitrophenyl)[3]ferrocenophane; DFT calculations on ferrocene derivatives

[3]Ferrocenophane (3a) reacts in a Gomberg reaction with diazotized p-nitroaniline to give a mixture of mono- and di-substituted products. The isomeric pairs of 3- and 2-(p-nitrophenyl)[3]ferrocenophanes (4 and 5), as well as 3,4′- and 3,4-bis-(p-nitrophenyl)[3]ferrocenophanes (6 and 7) were separated from the mixture by column chromatography on Al₂O₃ and characterized by means of mass, IR, UV, ¹H-NMR spectroscopy, and by X-ray analysis (4 and 6). PM3/tm and density functional theoretical calculations on ferrocene (1) and ferrocenophane derivatives are reported. A refined X-ray structure determination of [3]ferrocenophane (3a) is given.     

First enantioselective reductive amination of α-fluoroenones

From α-fluoroenones 2, a synthesis of (E) ketone oxime O-alkyl ethers 5 is reported with good to excellent yields. Then the first enantioselective reduction of these ketimines, via oxazaborolidine, is described with moderate to good enantiomeric excesses, leading to valuable chiral fluoroallylic amines 1.