Synthesis, chiroptical properties and photoinduced birefringence of optically active methacrylic copolymers bearing side-chain bisazoaromatic moieties

Three series of optically active photochromic copolymers, deriving from methyl methacrylate (MMA) and the chiral bisazoaromatic monomers (S)-3-methacryloyloxy-1-[4′-phenylazo-(4-azobenzene)]-pyrrolidine [(S)-MPAAP], (S)-3-methacryloyloxy-1-[4′-cyanophenylazo-(4-azobenzene)]-pyrrolidine [(S)-MPAAP-C] and (S)-3-methacryloyloxy-1-[4′-nitrophenylazo-(4-azobenzene)]-pyrrolidine [(S)-MPAAP-N], have been prepared and characterized in solution and in the solid state with the aim to evaluate the effect on their chiroptical and thermal properties originated by the insertion of inactive MMA groups along the main chain. The optical activity displayed by the bisazo polymers is discussed in terms of extent of chiral conformation assumed by the macromolecules as a consequence of dipole-dipole interactions between the bisazoaromatic chromophores.The photoinduction of birefringence has been assessed on thin films of the investigated copolymers in order to evaluate their behaviour as materials for optical data storage. The results are interpreted in terms of copolymer composition and conformational stiffness of the bisazoaromatic chromophoric co-units, which are responsible for the optical response rates, and are compared to those of the similar derivatives containing only one azo bond. The observed enhanced thermal properties and the temporal stability appear of interest for a potential use of these materials in nano technologies for all-optical data manipulation and in optoelectronics.     

Synthesis and chiroptical properties of optically active photochromic methacrylic polymers bearing in the side chain the (S)-3-hydroxypyrrolidinyl group conjugated with the trans-azoaromatic chromophore

Novel optically active polymethacrylates, namely poly[(S)-3-methacryloyloxy-1-(4-azobenzene)pyrrolidine] and poly[(S)-3-methacryloyloxy-1-(4′-nitro-4-azobenzene)pyrrolidine], have been synthesized by radical polymerization of the corresponding monomers, prepared in turn through a synthetic route preserving the asymmetric center by any racemization reaction. These homopolymers are characterized by the presence in the side chain of an optically active pyrrolidinyl ring linked to the trans-azoaromatic system through the nitrogen atom. The optical activity of the polymers in solution appears much higher than that observed with the low molecular weight models, purposely synthesized for comparison. Circular dichroism spectra of the synthesized products demonstrated that, in solution, the macromolecules assume highly homogeneous conformations with a prevailing chirality to a larger extent with respect to analogous systems previously investigated. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3257–3268, 1999     

Optically Active Methacrylic Polymers Bearing in the Side Chain the (S)-3-Hydroxypyrrolidinyl Group Linked to trans-bisazoaromatic Chromophore: Synthesis and Characterization

The synthesis by radical homopolymerization of a novel optically active methacrylic polymer containing a side-chain chiral moiety linked to a photochromic bisazoaromatic chromophore has been carried out starting from the related monomer (S)-3-methacryloyloxy-1-[4′-phenylazo-(4-azobenzene)]-pyrrolidine [(S)- MPAAP ]. The polymeric derivate has been fully characterized and its spectroscopic properties compared to those of the monomer and of the corresponding homopolymer bearing only one azoaromatic chromophore in the side chain. The optical activity displayed by the bisazo polymer is discussed in terms of extent of chiral conformation assumed by the macromolecules as a consequence of dipole-dipole interactions between the bisazoaromatic chromophores.     

A novel approach to Finafloxacin hydrochloride (BAY35-3377)

Finafloxacin hydrochloride, an important clinical compound was synthesized by a novel synthetic approach. An active intermediate ethyl 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate 19 was prepared by a new route. The chiral (S,S′)-N-Boc 10 was derived from protected pyrrolidine and the absolute stereochemistry was established by X-ray analysis.     

An efficient and stereoselective synthesis of (3S,4R)-(−)-trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

An asymmetric conjugate addition reaction between a chiral α,β-unsaturated amido ester and ethyl-N-methylmalonamide has been used as a key step in the synthesis of (3S,4R)-(−)-trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine, a key intermediate for (−)-paroxetine.     

Synthesis and optical properties of a poly(2′,5′-dioctyloxy-4,4′,4″- terphenylenevinylene) with high content of (Z) vinylene units

Poly(2′,5′-dioctyloxy-4,4′,4″-terphenylenevinylene) with (E) configuration of the vinylene double bonds was prepared by Suzuki-Miyaura polymerization of (E)-4,4′-dibromostilbene and 2,5-dioctyloxy-1,4-benzenediboronic acid. Attempts to extend this simple procedure to the synthesis of the polymer with (Z) configuration, starting from (Z)-4,4′-dibromostilbene, were unsuccessful. However, the use of (Z)-4,4′-diiodostilbene and a careful choice of Pd catalyst and experimental conditions, lead to a material with a >95/<5 (Z)/(E) ratio of vinylene units. The investigation of optical properties of both the (E) and (Z) polymers evidenced that (Z) linkages act as defects which reduce the effective conjugation length in the polymer backbone.     

Novel (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles from (E)- and (Z)-3-styrylchromones: the unexpected case of (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles

An efficient synthetic method for the preparation of (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles has been developed. The reaction of (E)- and (Z)-3-styrylchromones with hydrazine hydrate afforded the corresponding (E)- and (Z)-4-styrylpyrazoles, respectively, saved 4′-nitro-derivatives where both (E)- and (Z)-4′-nitro-3-styrylchromones afforded (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles. The reaction mechanism for these transformations was discussed and the stereochemistry of all products was assigned by NMR experiments.     

Methacrylic Polymers Bearing in the Side-Chain an Optically Active Moiety Linked to the trans-4-Azobenzene Chromophore: Chiroptical Properties of Poly[(S)-(+)-N-methyl-(2-methacryloyloxypropanoyl)-4-aminoazobenzene]

The synthesis by radical homopolymerization of a novel optically active methacrylic polymer containing a side-chain chiral moiety linked to a photochromic chromophore has been carried out starting from the related monomer trans-(S)-(+)-N-methyl-(2-methacryloyloxypropanoyl)-4-aminoazobenzene. The chiroptical properties in solution of the polymer have been investigated by circular dichroism and compared with those of the corresponding low molecular weight model compound, trans-(S)-(+)-N-methyl-(2-pivaloyloxypropanoyl)-4-aminoazobenzene. The optical activity displayed by the polymer is discussed in terms of extent of chiral conformations assumed by the macromolecules as a consequence of dipole-dipole interactions between the azoaromatic chromophores.     

Practical synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine

Three synthetic methods for the preparation of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, an important intermediate in the synthesis of the novel quinolone antitumor agent, AG-7352, have been developed. By one route, an efficient and large-scale preparation of the chiral pyrrolidine could be achieved through resolution of (±)-1-Boc-3-benzylamino-4-hydroxypyrrolidine, which is prepared from either 3-pyrroline or 1,4-dichloro-2-butene.     

Enantioselective synthesis of (R) and (S)-[9,9′]bi[naphtho(2,1-b)furanyl]-8,8′-diol: a furo-fused BINOL derivative

The enantioselective synthesis of [9,9′]bi[naphtho(2,1-b)furanyl]-8,8′-diol, a modified BINOL, was achieved using an inexpensive route. Both enantiomers of [9,9′]bi[naphtho(2,1-b)furanyl]-8,8′-diol were obtained with satisfactory stereoselectivities by employing two optical antipodes of phenylethylamine as chiral influence in a Cu(II)Cl₂ catalyzed oxidative coupling step.     

Nebenreaktionen bei der radikalischen,intramolekularen Cycloaddition von 2.6-Bis(2-methacryloyloxy-5-methylbenzyl)-4-methylphenylmethacrylat. Beitrag zu einer Matrizenreaktion

Zusammenfassung Die mit 2-Cyano-2-propylradikalen aus AIBN ausgel?ste und beendete intramolekulare Cycloaddition von 2,6-Bis(2-methacryloyloxy-5-methylbenzyl)-4-methylphenylmethacrylat (1) gibt die Cycloaddukte 4-Methyl-1,2,6-benzoltriyl-2,6-bis(4-methyl-2-methy-len-1,2-phenylen)-2,9-dicyano-2,3,5,7,9-pentamethyl-3, 5,7-dekantricarboxylat (1a) und -2,9-dicyano-2,3,5,8,9-pentamethyl-3,5,8-dekantricarboxylat (1b), welche molekulareinheitliche Leiteroligpmere vorstellen. Daneben bildeten sich 10-(2-Cyano-2-methylpropyl)8-(2-cyano-2-propyl)-4- {2-[(2-cyano-2-methylpropyl) acryloyloxy]-5-methylbenzyl∼-2,8,10,15-tetramethyl-7, 11-dioxo-dibenzo[b,e]-1,7-dioxacyclododekan-2,5-dien (1c) und 6 {2-[4-Cyano-2-(2-cyano-2-propyl)-2,4-dimethylvaleryloxy]-5-methylbenzyl}-4,4′-dimethyl-2,2′-methylendiphenyl-bis[2-(2-cyano-2-methylpropyl) acrylat] (1d). Bezogen auf den Ausgangsester1 konnten insgesamt 92% getrennte und dünnschicht-chromatographisch reine Reaktionsprodukte gefa?t werden. Die den Verbindungen zugeordneten Strukturen wurden mittels IR- und UV-Spektren sowie¹H-NMR- und massenspektrometrische Analyse gesichert. Die Cycloaddukte1a und1b sind Produkte einer synthetischen Matrizenreaktion(7), deren Ergebnisse an anderer Stelle mitgeteilt werden soll.

---

Summary The intramolecular cycloaddition of 2,6-bis(2-methacryloyloxy-5-methylbenzyl)-4-methylphenyl-methacrylate (1) was started and terminated by 2-cyano-2-propyl radicals from azoisobutyronitrile. The cycloadducts are 4-methyl-1,2,6-benzoltriyl-2,6-bis (4-methyl-2-methylene-1,2-phenylene)-2,9-dicyano-2,3, 5,7,9-pentamethyl-3,5,7-decanetricarboxylate (1a) and-2,9-dicyano-2,3,5,8,9-pentamethyl-3,5,8-decanetricarboxylate (1b), which are also molecularly uniform ladder oligomers. The side products are e]-1,7-dioxacyclododecane-2,5-diene (1c) and 6{2-[4-cyano-2-(2-cyano-2-propyl)-2,4-dimethylvaleryloxy]-5-methylbenzyl∼-4,4′-dimethyl-2,2′-methylenediphenyl-bis[2-(2-cyano-2 methylpropyl)acrylate] (1d). All together and relative to the starting ester1 92 % thin layer chromatographically pure reaction products could be isolated. The suggested structures of the compounds were confirmed by infrared and ultraviolet spectra as well as by¹H-NMR and mass spectroscopical analysis. The cycloadducts1a and1b are compounds of a matrix reaction (7). Their results will be published elsewhere.

---

---

Mit 3 Abbildungen und 5 Tabellen     

Chiral interactions in azobenzene dimers: a combined experimental and theoretical study

To investigate interchromophore interactions in azobenzene polymers, we have undertaken a thorough spectroscopic analysis of the azodye [(S)-3-pivaloyloxy-1-(4'-nitro-4-azobenzene)pyrrolidine] by modeling the repeating unit of poly[(S)-3-methacryloyloxy-1-(4'-nitro-4-azobenzene)pyrrolidine) and its dimeric derivative whose synthesis is presented here. The analysis of the electronic and Raman spectra of the azodye in several solvents is based on a previously proposed model for polar chromophores in solution. Electronic and CD spectra of the dimeric unit are collected and analyzed within the framework of a new model. On the basis of the information collected from the spectroscopic analysis of the solvated dye, this model accounts for interchromophore interactions in the dimer. The large CD signal measured for the dimer (amounting to about a third of the signal measured for the polymer) suggests the presence of important chiral interactions in the dimeric unit, and is modeled in terms of a right-handed relative orientation of the two chromophores.     

Efficient construction of a chiral all-carbon quaternary center by asymmetric 1,4-addition and its application to total synthesis of (+)-bakuchiol

The conjugate addition of lithium divinylcuprate to (4S,2′E)-3-(6′-TBDPS-3′-methylhex-2′-enoyl)-4-phenyloxazolidin-2-one proceeded efficiently to create a chiral all-carbon quaternary center with a high diastereoselectivity (R:S = 95:5). The absolute configuration of the newly generated chiral center was confirmed by applying this methodology to the total synthesis of (+)-bakuchiol.     

Efficient synthesis of the cyclopentanone fragrances (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone and Magnolione

This paper describes the selective syntheses of two cis-isomer-enriched cyclopentanone fragrances: (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone (four steps, 62% overall yield, 67% cis) and Magnolione^® (five steps, 60% overall yield, 55% cis). In addition, the asymmetric synthesis of (3aR,7aS)-5-methyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-one as well as (3a′R,7a′S)-5′-methyl-2′,3′,3a′,4′,7′,7a′-hexahydrospiro[[1,3]dioxolane-2,1′-indene] has been realized by an efficient kinetic resolution, which enables the selective synthesis of the 2S,3R-isomer-enriched 3 and 4.     

Synthesis of chiral 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine and their application to enantioselective borane reduction of prochiral ketones as chiral catalysts

Chiral diamines, 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine, were prepared from N-(tert-butoxycarbonyl)pyrrolidine or (S)-proline as a starting material, respectively. These chiral diamines were efficient for the catalytic enantioselective borane reduction of acetophenone. Using (S)-2-(anilinodiphenylmethyl)pyrrolidine, chiral secondary alcohols were obtained from prochiral ketones with good to excellent enantiomeric excesses (up to 98% ee).     

Efficient stereospecific synthesis of (S,S)-3-methoxy-4-methylaminopyrrolidine

Efficient stereospecific synthesis of (S,S)-3-methoxy-4-methylaminopyrrolidine, an important intermediate for a novel quinolone antitumor agent AG-7352 is presented. Starting from either d- or l-tartaric acid, a stereospecific synthesis of the chiral pyrrolidine was achieved via two S_N2 displacement reactions. From the results of this synthetic study, the absolute structure of AG-7352 was chemically determined.     

Synthesis and characterization of polybinaphthalene incorporating chiral (R) or (S)-1,1′-binaphthalene and oxadiazole units by Heck reaction

Chiral conjugated polymers P-1 and P-2 were synthesized by the polymerization of (R)-3,3′-diiodo-2,2′-bisbutoxy-1,1′-binaphthalene ((R)-M-1) and (S)-3,3′-diiodo-2,2′-bisbutoxy-1,1′-binaphthalene ((S)-M-1) with 2,5-bis(4-vinylphenyl)-1,3,4-oxadiazole (M-2) under Pd-catalyzed Heck coupling reaction, respectively. Both monomers and polymers were analysed by NMR, MS, FT-IR, UV, DSC-TG, fluorescent spectroscopy, GPC and CD spectra. The chiral conjugated polymers exhibit strong Cotton effect in their circular dichroism (CD) spectra indicating a high rigidity of polymer backbone. CD spectra of polymers P-1 and P-2 are almost identical and have opposite signs for their position. These polymers have strong blue fluorescence.     

Optically active polymers containing side-chain photochromic moieties. Synthesis and chiroptical properties of copolymers of trans-N(4-azobenzene)-maleimide with (−)-menthyl vinyl ether and (+)(S)-2-methylbutyl vinyl ether

The copolymers of trans-N(4-azobenzene)-maleimide (ABM) with optically active alkyl vinyl ethers, such as (?)-menthyl vinyl ether (MtVE) and (+)S-2-methylbutyl vinyl ether (MBVE), have been prepared either by direct copolymerization or by functionalization with trans-4-amino-azobenzene of the corresponding alternating copolymers of maleic anhydride with MtVE and MBVE. The chiroptical properties of the above copolymers have been studied by CD measurements. The induced optical activity on the side-chain trans-azobenzene moieties is discussed in terms of different conformational rigidity of the macromolecules.     

Stereoselective synthesis of new (+)-1-{(1R,3R,6S)-4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-yl}ethan-1-one derivatives

A procedure was developed for the stereoselective synthesis of aminated derivatives of (+)-1-{(1R,3R,6S)-4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-yl}ethan-1-one. The configuration of the side-chain chiral center in (+)-1-{(1R,3R,6S)-4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-yl}ethan-1-ol was determined by X-ray analysis. Diketene and Meldrum’s acid were proposed as initial compounds for the synthesis of, respectively, 3-oxobutanoic and malonic acid esters having a 1-ethyl-4,7,7-trimethylbicyclo[4.1.0]hept-4-ene fragment.     

Optically active polymers containing side-chain azobenzene moieties: Photochromic and photoresponsive behavior of copolymers of N-(4-azobenzene) maleimide with (−)-menthyl vinyl ether and (+) (S)-2-methylbutyl vinyl ether

Photochromic behavior and photoisomerization kinetics of optically active copolymers of trans-N-(4-azobenzene) maleimide (ABM) with (?) -menthyl vinyl ether (MtVE) and (+) (S) -2-methylbutyl vinyl ether were studied by UV spectroscopy under irradiation at 348 nm. The resulting data have been compared with those of the corresponding copolymers containing also trans-N-(4-azobenzene) maleamic acid co-units as well as of low molecular weight model compounds. The photoresponsive behavior has been also investigated by circular dichroism measurements at various extents of photoisomerization. The results are discussed in terms of structural requirements of the macromolecules. © 1994 John Wiley & Sons, Inc.