Enantiodifferentiating Photodimerization of a 2,6‐Disubstituted Anthracene Assisted by Supramolecular Double‐Helix Formation with Chiral Amines

A novel 2,6‐anthrylene‐linked bis(m‐terphenylcarboxylic acid) strand ( 1 ) self‐associates into a racemic double‐helix. In the presence of chiral mono‐ and diamines, either a right‐ or left‐handed double‐helix was predominantly induced by chiral amines sandwiched between the carboxylic acid strands with accompanying stacking of the two prochiral anthracene linker units in an enantiotopic face‐selective way, as revealed by circular dichroism and NMR spectral analyses. The photoirradiation of the optically active double helices complexed with chiral amines proceeded in a diastereo‐ (anti or syn) and enantiodifferentiating way to afford the chiral anti‐photodimer with up to 98 % enantiomeric excess when (R)‐phenylethylamine was used as a chiral double‐helix inducer. The resulting optically active anti‐photodimer can recognize the chirality of amines and diastereoselectively complex with chiral amines.     

Asymmetric Photochemical Synthesis of Chiral 5‐(R)‐(l)‐Menthyloxy‐4‐Cycloaminobutyrolactones

Through photocatalysed regiospecific and stereoselective additions of cycloamines to 5‐(R)‐(l)‐menthyloxy‐2 (5H)‐furanone (3), chiral 5‐(R)‐(l)‐menthyloxy‐4‐cycloaminobutyrolactones were synthesized. In the new asymmetric photoaddition of compound 3, the N‐methyl cyclic amines (4) gave novel chiral C? C photoadducts (5) in 24–50% isolated yields with d. e. ≥ 98%. However, the secondary cyclic amines (6) afforded optically active N? C photoadducts (7) in 34–58% isolated yields with d. e. ≥ 98% under the same condition. All the synthesized optically active compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]₅₈₉²⁰, IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The photosynthesis of chiral butyrolactones and its mechanism were discussed in detail.     

A Highly Efficient Synthesis of Optically Active Ferrocenylethylamines via Hydride Reduction of Chiral Ferrocenylketimines

Due to using (R)‐ or (S)‐α‐methylbenzylamine as a chiral auxiliary, and low‐temperature regime for reduction of the intermediate ferrocenyl‐mono‐ or 1,1′‐bis‐ketimines, the corresponding secondary mono‐ or 1,1′‐bis‐amines were prepared with high diastereoselectivity. Removal of the α‐methylbenzyl group afforded the optically active primary mono‐ and bis‐ferrocenylethylamines in high yields. The absolute configuration of (R,R)‐ 3a and (S,S)‐ 3b was determined by X‐ray single crystal diffraction.     

Free Energy Peturbation and Molecular Dynamics Simulation Studies on the Enantiomeric Discrimination of Amines by Dimethyldiketopyridino-18-Crown-6

Abstract

Discrimination of chiral amines by dimethyldiketopyridino-18-crown-6 (1) is studied by free energy peturbation (FEP) and molecular dynamics (MD) methods. 1 has two (S)-chiral centers and discriminates chiral amines through host-guest interactions. The optically active amines in this study are α-(1-naphthyl)ethylamine, methylbenzylamine, cyclohexylethylamine, and sec-butylamine. The trends in binding free energy differences obtained from FEP calculations were in excellent agreement with experimental results obtained in the gas phase. In order to explain the enantioselectivity of the host in terms of the host-guest interactions at the molecular level, we analyzed the structures generated by 10-ns MD simulations of host-guest complexes. The suggested chiral discrimination mechanism, the π-π interaction and the steric repulsion between the guest and the host, was verified by our MD simulation analysis.     

Asymmetric Syntheses XXVI: Catalytic Enantioselective Syntheses of β-Hydroxy Esters via Double Chiral Induction in Asymmetric Reformatsky Reactions

Catalytic asymmetric Reformatsky reactions of benzaldehyde with optically active menthyl bromoacetates in the presence of Zn-Cu couple were performed using 0.25 equiv. of (1R,2S) or (1S,2R)-dimethyl-2-amino-1,2-diphenyl ethanol as chiral ligand to obtain β - hydroxy esters with enantioselectivities up to 60.2%. The obvious double chiral induction effect was observed while chiral ligands matched with optically active substrates.     

Synthesis of optically-active benzylic amines; asymmetric reduction of ketoxime ethers with chiral oxazaborolidines

The preparation of novel optically active benzylic amines by the enantioselective reduction of phenone oximes using chiral oxazaborolidine is described. The choice of the chiral 1,2-amino alcohol (S)-diphenylvalinol as chiral inducer and that of the benzyl group for the O-oxime substituent is explained. 23 primary amines are obtained, with high enantioselectivity (e.e.=98%), good yield (74%) on preparative scale. A mechanistic explanation is proposed.     

Unexpected Thermally Stable,Cholesteric Liquid‐Crystalline Helical Polyisocyanides with Memory of Macromolecular Helicity

The achiral sodium salt of poly(4‐carboxyphenyl isocyanide) (poly‐ 1 –Na) folds into a one‐handed helix induced by optically active amines in water. The induced helicity remains when the optically active amines are completely removed, and further modification of the side groups to amide residues is possible without loss of memory of macromolecular helicity. Although the helical poly‐ 1 –Na loses its chiral memory at high temperature, helical polyisocyanides modified with achiral primary amines, which no longer have any chiral components, keep their memory perfectly even at 100 °C in N,N‐dimethylformamide in some cases and exhibit cholesteric liquid‐crystalline phases, thus providing a robust scaffold with heat resistance to which a variety of functional groups can be introduced.     

Novel highly fluorescent dendritic chiral amines: synthesis and optical properties

An efficient approach to dendritic chiral amines through the allylation of optically active imines bearing chiral auxiliaries were developed. The addition of allylic zinc catalyzed by CeC1₃·7H₂O to chiral imines derived from 2-thiophenecarboxaldehyde and α-amino acid esters conveniently and efficiently afforded the corresponding homoallylic amines with excellent diastereoselectivity. Such addition reactions employing diimines or triimines of the polycyclic aromatic derivatives also produced the chrial multiallylic dendritic amines with the similar diastereoselectivity. The investigation of their photophysical properties including UV-vis absorption and fluorescence spectra as well as circular dichroism (CD) indicated that it did not affect the absorption of the precursors to induce the chiral auxiliaries; however, that the whole molecules exhibited the obvious CD behaviors.     

Stereo- and regioselectivity in asymmetric synthesis of α-amino substituted benzocyclic compounds

The enantiomerically pure chiral benzocyclic amines 6–8 were obtained by asymmetric transamination of the corresponding prochiral ketones 9a–c. The method involves: (a) formation of chiral imines 10a–c from the prochiral ketones 9a–c and the inexpensive chiral auxiliary (R)- or (S)-phenylethylamine (PEA); (b) asymmetrically induced reduction of these imines to the diastereomeric amines 11a–c and 12a–c; (c) catalytic hydrogenation to remove the benzylic fragment of the chiral PEA auxiliary. The stereoselectivity of the imine reduction, as well as the regioselectivity of the catalytic hydrogenation, are strongly dependent on the size of the saturated ring condensed with the benzene ring. This approach was used to develop a convenient, high yielding, and stereoselective route to several practically important optically active α-amino substituted benzocyclic compounds.     

Editorial

Abstract

Asymmetric syntheses of optically active polymethacrylate, polyacrylate, polyacrylamide, and polyisocyanate with helical conformation and their chiral recognition abilities are described. 1-Phenyldibenzosuberyl methacrylate (PDBSMA) gave a purely onehanded-helical, optically active polymer ([α]₃₆₅ +1670 ～ +1780º) with almost perfectly isotactic structure by anionic polymerization using optically active initiators. Radical polymerizations of PDBSMA using chiral initiators, chain transfer agents, and additives also afforded optically active polymers with a prevailing onehanded helicity. Triphenylmethyl acrylate yielded an optically active, helical polymer ([α]₃₆₅ +102º) having a dyad isotacticity of 70% using an optically active anionic initiator. Although the polyacrylate demonstrated chiral recognition ability as a chiral stationary phase for HPLC, the ability was low mainly because of the low degree of one-handedness. N-(3-Chlorophenyl)-N-phenylacrylamide gave an optically active, helical polymer ([α]_365–343º) in the asymmetric anionic polymerization; the polymer had a dyad tacticity of 77%. Optically active polyisocyanates with a predominantly one-handed helical conformation were prepared in homo-and co-polymerization of optically active phenyl isocyanate derivative. These polyisocyanates showed the ability to discriminate enantiomers in solution.     

Alcohol Dehydrogenases with anti-Prelog Stereopreference in Synthesis of Enantiopure Alcohols

Biocatalytic production of both enantiomers of optically active alcohols with high enantiopurities is of great interest in industry. Alcohol dehydrogenases (ADHs) represent an important class of enzymes that could be used as catalysts to produce optically active alcohols from their corresponding prochiral ketones. This review covers examples of the synthesis of optically active alcohols using ADHs that exhibit anti-Prelog stereopreference. Both wild-type and engineered ADHs that exhibit anti-Prelog stereopreference are highlighted.     

An asymmetric synthesis of carboxylic acid derivatives,including lactic acid and α-amino acid derivatives,from optically active 1-chlorovinyl p-tolyl sulfoxides and ester lithium enolates with creation of chirality at the α-position

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from symmetrical ketones or methyl formate and (R)-(−)-chloromethyl p-tolyl sulfoxide in three steps, with lithium enolate of carboxylic acid tert-butyl esters gave optically active adducts having a substituent (alkyl, alkoxy, or dibenzylamino group) at the α-position with high 1,4-chiral induction from the sulfur chiral center. The adducts were converted to optically active esters, lactic acid, and α-amino acid derivatives having a chiral center at the α-position. When this addition reaction was carried out with an ester enolate generated from excess carboxylic acid tert-butyl ester with LDA in the presence of HMPA, the diastereomer of the adduct was obtained. By using the two reaction conditions for the generation of the ester enolate, a new method for asymmetric synthesis of both enantiomers of carboxylic acid derivatives having a substituent at the α-position from the one chiral source, (R)-(−)-chloromethyl p-tolyl sulfoxide, was achieved.     

Homo‐double helix formation of an optically active conjugated polymer bearing carboxy groups and amplification of the helicity upon complexation with achiral and chiral amines

An optically active, m‐terphenyl‐based π‐conjugated polymer bearing carboxy groups was synthesized by the copolymerization of the diethynyl monomer bearing a carboxy group with (S,S)‐2,5‐bis(2‐methylbutoxy)‐1,4‐dibromobenzene using Sonogashira reaction. The copolymer showed a weak circular dichroism (CD) in the main‐chain chromophore region due to a homo‐double helix formation with an excess helical handedness biased by the chiral alkoxy substituents through self‐association. However, upon complexation with achiral amines, such as piperidine, the CD intensity of the polymer significantly increased resulting in the formation of a greater excess one‐handed homo‐double helix via hydrogen‐bonded inclusion complexation with the achiral amines between each strand, leading to the amplification of the helicity. A preferred‐handed homo‐double helix was also induced in the polymer in the presence of nonracemic amines. The effect of the achiral and chiral amines on the homo‐double helix formation was investigated by comparing the CD spectra of the polymer to those of its model dimer. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 990–999     

Synthesis of optically enriched 1,2-aminoalcohols by [2,3]-Wittig rearrangements of 3-aza-allylic alcohol derivatives

[2,3]-Wittig rearrangements of (E)-3-aza-allylic alcohol derivatives can provide access to syn or anti optically enriched 1,2-aminoalcohols by using a chirality transfer or a chiral auxiliary.     

Synthesis of New MeO-BIPHEP-type Chiral Diphosphines by an Improved Way

In this paper,a series of new optically active MeO-BIPHEP-type ligands,(S)-6,6'-dimethoxy-2,2'-bis(di-p-alkoxyphenyl-phosphine)-1,1'-biphenyl[(S)-5b—(S)-5e]were prepared and characterized.Starting from thecommercially available triethyl phosphorite and m-bromoanisole,an optically active(S)-6,6'-dimethoxybiphenyl-2,2'-diyl-bis(phosphonic acid diester)was prepared by an improved way and converted to the corresponding dichlo-rides,which was used as a key intermediate to react with p-alkoxybenzenemagnesium bromide or p-alkoxyphenyllithium to directly give the enantiomerically pure diphosphines 5.     

A novel method for asymmetric synthesis of both enantiomers of α-substituted carboxylic acid derivatives from optically active 1-chlorovinyl p-tolyl sulfoxides and lithium ester enolates with 1,4-chiral induction from the sulfur chiral center

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from symmetrical ketones and (R)-(−)-chloromethyl p-tolyl sulfoxide in three steps, with lithium enolate of carboxylic acid tert-butyl esters gave optically active adducts having a substituent at the α-position with high 1,4-chiral induction from the sulfur chiral center in high yields. The adducts were converted to optically active esters and carboxylic acids having a chiral center at the α-position. When this addition reaction was carried out with the ester enolate generated from excess carboxylic acid tert-butyl ester with LDA in the presence of HMPA, the diastereomer of the adduct was obtained. By using the two reaction conditions for the generation of the ester enolates, a new method for asymmetric synthesis of both enantiomers of carboxylic acid derivatives having a substituent at the α-position from the one chiral source, (R)-(−)-chloromethyl p-tolyl sulfoxide, was realized.     

Three-component chiral derivatizing protocols for NMR spectroscopic enantiodiscrimination of hydroxy acids and primary amines

The novel three-component chiral derivatization protocols have been derived for (1)H and (19)F NMR spectroscopic discrimination of a series of chiral hydroxy acids by their coordination and self-assembly with optically active α-methylbenzylamine and 2-formylphenylboronic acid. In addition, the optically pure (S)-mandelic acid in combination with 2-formylphenylboronic acid permits visualization of enantiomers of primary amines. These protocols have been demonstrated on enantiodiscrimination of chiral amines and hydroxy acids.     

Macromolecular helicity inversion of poly(phenylacetylene) derivatives induced by various external stimuli

Unique macromolecular helicity inversion of stereoregular, optically active poly(phenylacetylene) derivatives induced by external achiral and chiral stimuli is briefly reviewed. Stereoregular, cis-transoidal poly(phenylacetylene)s bearing an optically active substituent, such as (1R,2S)-norephedrine (poly- 1 ) and β-cyclodextrin residues (poly- 2 ), show an induced circular dichroism (ICD) in the UV-visible region of the polymer backbone in solution due to a predominantly one-handed helical conformation of the polymers. However, poly- 1 undergoes a helix-helix transition upon complexation with chiral acids having an R configuration, and the complexes exhibit a dramatic change in the ICD of poly- 1 . Poly- 2 also shows the inversion of macromolecular helicity responding to molecular and chiral recognition events that occurred at the remote cyclodextrin residues from the polymer backbone; the helicity inversion is accompanied by a visible color change. A similar helix-helix transition of poly((R)- or (S)-(4-((1-(1-naphthyl)ethyl)carbamoyl)phenyl)acetylene) is also briefly described.     

Isosteviol‐amino Acid Conjugates as Highly Efficient Organocatalysts for the Asymmetric One‐pot Three‐component Mannich Reactions

Isosteviol‐amino acid conjugates were synthesized and used as chiral catalysts for the asymmetric three‐component Mannich reaction with hydroxyacetone as donor molecule. Good yields (up to 98%) and excellent stereoselectivities (up to 97:3 dr and 99% ee) were achieved in a short reaction time. In addition, syn‐ or anti‐configurations of α‐hydroxy‐β‐amino carbonyl compounds were obtained as main products with different chiral catalysts.     

A Simple Diastereoselective Synthesis of Chiral Nonracemic Aliphatic Amines

An efficient procedure has been developed for the diastereoselective synthesis of chiral aliphatic amines (diastereoisomeric excess >96%) from (1S)-N-(1-methylethylidene)-1-phenylethylamine, i.e., Schiff base derived from the simplest ketone (acetone) and (1S)-1-phenylethylamine. The procedure includes successive lithiation, alkylation, and reduction and is characterized by high regioselectivity in the formation of alkylated syn-Z-imines. Hydride reduction of the prochiral C=N bond in the latter gives mainly optically active aliphatic amines with R configuration. All reactions are performed as a one-pot process without isolation of intermediate products.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 827–831.Original Russian Text Copyright © 2005 by Grishina, Luk’yanenko, Borisenko.