Achiral Imines Research Articles

Chirally and chemically reversible Strecker reaction.

In the pursuit of a credible mechanism for the abiotic synthesis of α-amino acids, solid-state asymmetric Strecker/retro-Strecker reactions have been demonstrated. Asymmetric addition of cyanide to enantiomorphic crystals of achiral imines proceeded to produce enantioenriched aminonitriles. Moreover, dehydrocyanation of enantioenriched aminonitriles gave chiral crystals of achiral imines stereoselectively. We found, for the first time to the best of our knowledge, a stereoinversion of the synthetic intermediates imine and aminonitrile in the sequence of reactions including HCN addition and elimination. Thus, the reversible Strecker reaction is expected to be a focus of research on the origin of chirality.

Asymmetric Strecker Reaction Arising from the Molecular Orientation of an Achiral Imine at the Single-Crystal Face: Enantioenriched l- and d-Amino Acids.

Strecker synthesis has long been considered one of the prebiotic reactions for the synthesis of α-amino acids. However, the correlation between the origin of chirality and highly enantioenriched α-amino acids through this method remains a puzzle. In the reaction, it may be conceivable that the handedness of amino acids has been determined at the formation stage of the chiral intermediate α-aminonitrile, that is, the enantioselective addition of hydrogen cyanide to an imine. Herein, an enantiotopic crystal surface of an achiral imine acted as an origin of chirality for the enantioselective formation of α-aminonitriles by the addition of HCN. In conjunction with the amplification of the enantiomeric excess and multiplication of enantioenriched aminonitrile, a large amount of near enantiopure α-amino acids, with the l- and d-handedness corresponding to the molecular orientation of the imine, is reported.

Asymmetric Strecker Reaction Arising from the Molecular Orientation of an Achiral Imine at the Single‐Crystal Face: Enantioenriched l‐ and d‐Amino Acids

AbstractStrecker synthesis has long been considered one of the prebiotic reactions for the synthesis of α‐amino acids. However, the correlation between the origin of chirality and highly enantioenriched α‐amino acids through this method remains a puzzle. In the reaction, it may be conceivable that the handedness of amino acids has been determined at the formation stage of the chiral intermediate α‐aminonitrile, that is, the enantioselective addition of hydrogen cyanide to an imine. Herein, an enantiotopic crystal surface of an achiral imine acted as an origin of chirality for the enantioselective formation of α‐aminonitriles by the addition of HCN. In conjunction with the amplification of the enantiomeric excess and multiplication of enantioenriched aminonitrile, a large amount of near enantiopure α‐amino acids, with the l‐ and d‐handedness corresponding to the molecular orientation of the imine, is reported.

An Efficient Microwave Method for the Synthesis of Imines

A large variety of aryl and heterocyclic chiral and achiral imines can be generated simply, efficiently, and cleanly through the use of microwave irradiation and the use of a small amount of molecular sieve. Reactions are rapid and complete in a matter of minutes, and can be quantitative, reducing significantly the time and amount of solvents used in compound isolation and purification.

New Chiral and Achiral Imines and Bisimines Derived from 2‐Phenyl‐1H‐imidazole‐4‐carbaldehyde. Synthesis, Structural Studies and Complexation Stability Constants

Synthesis and properties of new imines and bisimines derived from 2‐phenyl‐1H‐imidazole‐4‐carbaldehyde and amines/diamines were studied. (2‐Phenyl‐1H‐imidazole‐4‐yl)methanol was oxidized to 2‐phenyl‐1H‐imidazole‐4‐carbaldehyde with better yield 55% by the modification of literature procedure. This aldehyde was condensed with the following achiral and chiral amines or 1,2‐diamines: ethanamine, propan‐1‐amine, butan‐1‐amine, 2‐methylpropan‐1‐amine, cyclohexanamine, (2R)‐ and (2S)‐3‐methylbutan‐2‐amine, (1R)‐ and (1S)‐1‐cyclohexylethanamine, (S)‐1‐aminopropan‐2‐ol, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)ethanamine, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)‐2‐methylpropan‐1‐amine, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)‐3‐methylbutan‐1‐amine, ethane‐1,2‐diamine, and (1R,2R)‐ and (1S,2S)‐cyclohexane‐1,2‐diamine. Sixteen condensation products, especially chiral imines and bisimines, were prepared by founded procedures in 45–99% of yields and characterized by the 1H NMR spectroscopy in solution, mass spectrometry, and elemental analyses. The optical rotation values in the case of chiral ones were also observed. Stability constants of Cu(II) complexes of selected prepared imines/bisimines were determined.

Remote stereocontrol in reactions between 4- and 5-alkoxyalk-2-enylstannanes and 1-alkoxycarbonylimines and analogues: stereoselective approaches to novel α-amino acids

Reactions of the allyltin trichloride 45 generated from (4S)-4-benzyloxypent-2-enyl(tributyl)stannane 1 with imines prepared from glyoxylates proceed with useful levels of 1,5-stereocontrol in favour of (4E)-2,6-anti-2-(alkylamino)-6-benzyloxyhept-4-enoates 49. This stereoselectivity, controlled by the chirality of the stannane, dominates over any intrinsic stereochemical bias of the imine although a small amount of matching and mis-matching was observed. The allyltin trichloride 77 prepared from (4S)-4-(tert-butyldimethylsilyloxy)pent-2-enyl(tributyl)stannane 52 reacts with 1-alkoxycarbonylimines with the opposite 1,5-stereoselectivity to give the (4E)-2,6-syn-diastereoisomers 79. Matching and mismatching was more pronounced for tin(IV) chloride mediated reactions of (4R)-5-benzyloxy-4-methylpent-2-enyl(tributyl)stannane 80 with chiral 1-alkoxycarbonylimines but useful stereoselectivity in favour of (4E)-2,6-syn-2-alkyl- and arylthio-amino-7-benzyloxy-6-methylhept-4-enoates 177 was observed for reactions with achiral imines and similar, but reduced, stereoselectivity was observed for the 5-tert-butyldimethylsilyloxypentenylstannane 82. However, excellent 1,5-stereocontrol in favour of the (4E)-2,6-anti-isomers 179 was found using the 4,5-bis-alkoxypent-2-enylstannane 106. Modest (4E)-2,7-anti-stereoselectivity was observed in the analogous tin(IV) bromide mediated reactions of (S)-5-methoxy- and (S)-5-hydroxyhex-2-enyl(tributyl)stannanes (S)-123 and (S)-122 with achiral 1-alkoxycarbonylimines but in this series the intrinsic stereochemical bias of the imine controls the facial selectivity of reactions of chiral 1-alkoxycarbonylimines. Useful (4E)-2,6-anti-stereoselectivity was also observed in the tin(IV) chloride promoted reaction of the 4-benzyloxypent-2-enylstannane 1 with an oxime O-benzyl ether.

Asymmetric addition of diethylzinc to aldehydes catalyzed by new zinc-amides prepared by a rhodium-catalyzed asymmetric addition

A new chiral zinc-amide 2s′ was found to be an effective catalyst for the asymmetric addition of diethylzinc to aldehydes 3 through a screening method for asymmetric catalysts, in which two catalytic asymmetric reactions are connected. The chiral zinc catalyst can be readily prepared catalytically from achiral imine 1 by the chiral rhodium–diene complex mediated asymmetric addition of dimethylzinc.

ChemInform Abstract: A Stereoselective Synthesis of the (2R,3S)- and (2S,3R)-3-Amino-2- hydroxybutyric Acid Derivatives, the Key Components of a Renin Inhibitor and Bestatin.

Abstract The title synthesis was achieved by featuring the [2+2]-cycloaddition reaction of benzyloxyketene with a chiral imine derived from methyl (R)- or (S)-mandelate, alcoholysis of the formed 3,4-cis disubstituted β-lactam under acidic conditions, and reductive removal obtained by the [2+2]-cycloaddition reaction employing achiral and chiral imines derived from benzylamine, p-anisidine, di-panisylmethylamine, and (S)-l-phenylethylamine were also reported. Stereoselectivity of the [2+2]-cycloaddition reaction could be explained by the initial formation of a zwitter-ionic intermediate and its subsequent conrotatory ring closure.

Asymmetric synthesis of anticancer β-lactams via Staudinger reaction: Utilization of chiral ketene from carbohydrate

We describe herein asymmetric synthesis of a novel anticancer β-lactam following Staudinger reaction with chiral carbohydrate as the ketene component with an achiral imine. The in vitro cytotoxicity studies of these β-lactams are also reported here.

Boron‐Based Diastereomerism and Enantiomerism in Imine Complexes – Determination of the Absolute Configuration at Boron by CD Spectroscopy

AbstractBoron turns out to be a stable stereogenic center in imine complexes of aryl and alkyl boronates. Diastereomerically pure complexes 7a–c are obtained from chiral imine ligands 5a,b that are derived from the amino alcohol (R)‐4. The configuration at the boron atom is determined by crystal structure analyses. Racemic boronates 10a–c, available from a condensation of aryl boronic acids 6 with the achiral imine ligand 9, can be separated into stable enantiomers by HPLC on a chiral column. The racemization barrier ΔG≠ has been determined to amount to 105–115 kJ mol–1. The comparison of calculated and measured CD spectra permits to assign unambiguously the absolute configuration to boron in the enantiomeric boronate‐imine complex 10a.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Asymmetric aza-Michael reactions of alpha,beta-unsaturated ketones with bifunctional organic catalysts.

Asymmetric aza-Michael reactions of alpha,beta-unsaturated ketones with bifunctional organic catalysts.

Imino‐Diels–Alder Reactions of 1‐Aryl‐3‐(trialkylsiloxy)‐1,3‐butadienes in Solution and the Solid Phase

AbstractImino‐Diels–Alder reactions between 1‐aryl‐ or 1‐heteroaryl‐3‐(trialkylsiloxy)‐1,3‐butadienes and imines derived from ethyl glyoxylate have been studied. When an achiral imine was used, the diastereoselectivity depended on the nature of the aryl or heteroaryl system; diastereoselectivities > 90 % were observed with methoxyphenyl or indolyl substituents, but were much lower for nitro substituents. High diastereoselectivities were also achieved if a chiral imine derived from methylbenzylamine was used as the dienophile. Solid‐supported imine dienophiles yielded the N‐deprotected cycloadducts by direct cleavage from the resin with no diastereoselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Asymmetric Intramolecular Alkylation of Chiral Aromatic Imines via Catalytic C-H Bond Activation

The asymmetric intramolecular alkylation of chiral aromatic aldimines, in which differentially substituted alkenes are tethered meta to the imine, was investigated. High enantioselectivities were obtained for imines prepared from aminoindane derivatives, which function as directing groups for the rhodium-catalyzed C-H bond activation. Initial demonstration of catalytic asymmetric intramolecular alkylation also was achieved by employing a sterically hindered achiral imine substrate and catalytic amounts of a chiral amine.

Highly Stereoselective Reactions of γ‐Sulfinyl Carbanions with Achiral Imines

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Stereoselective Reactions of γ-Sulfinyl Carbanions with Achiral Imines

Lithium 2-p-tolylsulfinylbenzyl carbanions react with different N-substituted imines affording 1,2-diaryl ethyl (and propyl) amines with a high stereoselectivity control at both benzyllic (only dependent of the sulfur configuration) and iminic carbons. The anti:syn ratio, ranging between > 96: < 4 and < 2: > 98, dependent on the electronic density at nitrogen.

Phase Transfer Catalyzed Asymmetric Alkylations of Imine Glycinamides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Phase transfer catalyzed asymmetric alkylations of imine glycinamides

Herein we report the use of achiral imine glycinamides as substrates for asymmetric alkylations using chiral phase-transfer catalysts for the first time. Initially tried for obtaining a key intermediate for the synthesis of levobupivacaine, we expanded the study to other N-mono and N, N-disubstituted imine glycinamides. A possible explanation for the lower enantioselectivity observed in the case of alkylation of N-monosubstituted as compared to N, N-disubstituted glycinamides is also provided.

A Switch of Enantiofacial Selectivities Using Designed Similar Chiral Ligands in Zirconium-Catalyzed Asymmetric Aza Diels−Alder Reactions

Synthesis of both enantiomers is a very important task not only in organic chemistry but also in medicinal and bioorganic chemistry.1 In chemical transformations, syntheses of both enantiomers are generally carried out using both enantiomers of chiral sources. While there are many chiral sources in nature, it is sometimes difficult to obtain both enantiomers, for instance, those of amino acids, monosaccharides, alkaloids, etc. When such chiral sources are employed in asymmetric syntheses, preparation of both enantiomers is difficult. On the other hand, from a mechanistic point of view, both enantiomers can be produced by controlling the enantiofaces of prochiral compounds. Therefore, it would be possible to control them by designing ligands that even have the same chirality.2,3 In this paper, we report an example of this; a switch of enantiofacial selectivities using similar types of ligands in chiral zirconiumcatalyzed aza Diels-Alder reactions. Recently, we reported the first enantioselective aza DielsAlder reactions of imino dienophiles using a chiral zirconium catalyst (1) prepared from Zr(O-t-Bu)4, (R)-6,6′-dibromo-1,1′binaphthol ((R)-Br-BINOL), and N-methylimidazole (NMI).4-6 According to these reactions, optically active piperidine derivatives having an S-configuration were prepared from achiral imines and 1-methoxy-3-trimethylsiloxy-1,3-butadiene (Danishefsky’s diene,7 2) in high enantioselectivities. In the course of our investigations to examine the catalystsubstrate interaction including the reaction course and to improve selectivities, it was indicated from both experiments and modeling studies that the substituents on the 3,3′positions of the BINOL ligand influenced the enantioselectivities strongly.8 We prepared 3,3′-substituted BINOL (3 and 4).9 In the presence of Zr(OBu)4 (20 mol %), (R)-6,6′-

Catalytic asymmetric aza Diels-Alder reactions using a chiral lanthanide Lewis acid. Enantioselective synthesis of tetrahydroquinoline derivatives using a catalytic amount of a chiral source

In the presence of a catalytic amount of the chiral ytterbium Lewis acid, which was prepared from Yb(OTf) 3, (R)-(+)-BINOL, diazabicyclo[5.4.0]undec-7-ene (DBU), and an additive, achiral imines reacted with achiral dienophiles to afford the corresponding tetrahydroquinoline derivatives in high yields with high diastereo- and enantioselectivities. This is the first example of aza Diels-Alder reactions using a catalytic amount of a chiral source.

β‐ラクタム環構築における異なる金属種を用いる立体化学のスイッチング

The importance of the stereodivergent synthesis of both enantiomers of β-lactams is ever increasing in connection with the structure-activity relationship study and the development of new derivatives in the β-lactam antibiotics. In this account stereocontrol at the C-3 and C-4 carbons of β-lactams using metal ester enolate-imine condensation reactions is discussed. The addition of an achiral ester enolate with a chiral imine possessing a dioxolane ring derived from (2S, 3S)-1, 4-dimethoxy-2, 3-butanediol as a chiral auxiliary is presented, in which 4-monosubstituted, 3, 4-disubstituted, and 3, 3, 4-trisubstituted β-lactams are prepared in a highly stereodivergent manner simply by switching metal ester enolate species. The application to the stereoselective synthesis of 1β-methylcarbapenem from 4-monosubstituted β-lactam is conducted by the use of selective hydrogenation reaction as a crucial step. The addition of an achiral ester enolate with a chiral imine having an auxiliary derived from phenylglycine at the nitrogen and the reaction of a chiral ester possessing arylsulfinyl group as an auxiliary at the α-position to the carbonyl with an achiral imine are also described for the stereodivergent synthesis of each of β-lactams from a single chiral source.