High Levels Of Diastereoselectivity Research Articles

Diastereoselective intramolecular aldol ring closures of threonine derivatives leading to densely functionalised pyroglutamates related to oxazolomycin

Intramolecular aldol reactions on oxazolidine templates derived from threonine may be used to generate libraries of densely functionalised pyroglutamates with a high level of diastereoselectivity.

Pictet–Spengler reactions of oxetan-3-ones and related heterocycles

Pictet–Spengler reactions of oxetan-3-ones and azetidin-3-ones with tryptamine and tryptophan derivatives produce spirocyclic tetrahydro-β-carbolines in good yields. Molecular iodine (5mol%) is an effective catalyst in most cases and high levels of diastereoselectivity are witnessed using 2-substituted oxetan-3-ones.

Organocatalytic formal [5+1] annulation: diastereoselective cascade synthesis of functionalized six-membered spirocyclic indane-1,3-diones/oxindoles via Michael–aldol reaction

An efficient cascade protocol has been developed for the diastereoselective synthesis of functionalized six-membered spirocyclic compounds. The reaction proceeded smoothly between indane 1,3-diones/oxindoles/coumaranone as the dinucleophilic components and (E)-5-nitro-6-aryl-hex-5-en-2-one as the dielectrophile to give the desired products with reasonable to high chemical yields (30–84%) and high levels of diastereoselectivities (upto >95:5 dr). The reaction proceeded smoothly via cascade Michael–aldol reaction.

Boron‐Containing Peptidomimetics – A Novel Class of Selective Anti‐tubercular Drugs

Medical treatment for tuberculosis is complicated nowadays by the appearance of new multiresistant strains, and therefore, new antibiotics are in great need. Here, we report the synthesis and in vitro testing of a new class of highly selective antimicrobial boron-containing peptidomimetics with compounds exhibiting activity against Mycobacterium tuberculosis at ≤5 μg/mL. The new approach developed makes it possible to synthesize variously substituted β-aminoboronic acids and their derivatives with a high level of diastereoselectivity.

Synthesis and Characterization of Monosaccharide Derivatives and Application of Sugar‐Based Prolinamides in Asymmetric Synthesis

AbstractFor the first time, the β‐anomer of N‐acetylglucosamine derivative methyl 2‐acetamido‐3,4,6‐tri‐O‐benzyl‐2‐deoxy‐β‐D‐glucopyranoside (9b) was synthesized, isolated, and used in the synthesis of sugar‐based primary amine 4b. Sugar‐based primary amine 5a, an anomeric pair of monosaccharide derivatives 6a and 6b, and precursors to all these compounds were also synthesized, isolated, and well studied by standard spectroscopic methods, including 2D NMR spectroscopy experiments such as 1H–1H COSY and HSQC. Then sugar‐based primary amines 4a, 5a, 6a, and 6b were converted into the corresponding prolinamide organocatalysts (i.e., 1a, 2a, 3a, and 3b) in high yields. The catalytic activity of these sugar‐based prolinamide organocatalysts was demonstrated in asymmetric aldol reactions in various solvents and at different temperatures. The oraganocatalyst 3a was shown to be an efficient and powerful organocatalyst for the enantioselective aldol reaction of various cyclic or acyclic ketones with aromatic aldehydes in a mild and facile reaction, which gave the corresponding aldol adducts with high levels of diastereoselectivity (up to 99:1) and enantioselectivity (up to >99 %) in almost all cases.

ChemInform Abstract: Enantioselective Synthesis of Optically Active cis‐β‐Thio‐α‐amino Acid Derivatives Through an Organocatalytic Cascade Thio‐Michael/Ring Opening Process.

Non-naturally enantioenriched cis-β-thio-α-amino acid derivatives were synthesized through one pot, cascade thio-Michael/ring opening reaction of aromatic thiols with (Z)-olefinic azlactones in good yields with high levels of diastereoselectivities and enantioselectivities, which was catalyzed by a chiral bifunctional thiourea–tertiary amine catalyst.

An acyl-Claisen approach to the synthesis of lignans and substituted pyrroles

The acyl-Claisen rearrangement, also called a zwitterionic aza-Claisen rearrangement, allows for the synthesis of 2,3-syn-substituted morpholine pent-4-eneamides with high levels of diastereoselectivity. A wide variety of alkyl and aryl substituents can be introduced with yields highly dependent on the stoichiometry of the Lewis acid catalyst. The use of these morpholine amides in the synthesis of the tetrasubstituted tetrahydrofuran lignans fragransin A2, talaumidin, and galbelgin is summarized. The conversion of the Claisen-derived amides into aryl tetraline and 1,1-diarylbutanol lignans via alteration of the protecting groups is also described. Nucleophilic addition of an organometallic reagent to the morpholine amide followed by Wacker oxidation of the alkene gives highly substituted 1,4-diketones, which can be easily converted into fully substituted pyrroles.

Enantioselective synthesis of optically active cis-β-thio-α-amino acid derivatives through an organocatalytic cascade thio-Michael/ring opening process

Non-naturally enantioenriched cis-β-thio-α-amino acid derivatives were synthesized through one pot, cascade thio-Michael/ring opening reaction of aromatic thiols with (Z)-olefinic azlactones in good yields with high levels of diastereoselectivities and enantioselectivities, which was catalyzed by a chiral bifunctional thiourea-tertiary amine catalyst.

Diastereoselective Synthesis of 1,3,5-Trisubstituted 4-Nitropyrrolidin-2-ones via a Nitro-Mannich/Lactamization Cascade

A versatile one-pot nitro-Mannich/lactamization cascade for the direct synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones has been developed. The reaction is easy to perform and broad in scope, and high levels of diastereoselectivity can be achieved.

ChemInform Abstract: FeCl3‐Promoted One‐Step Synthesis of Spiro[4.5]decane Derivatives.

AbstractDehydration of various cyclopentanol substrates followed by Prins cyclization affords the desired structural units with a high level of diastereoselectivity.

ChemInform Abstract: Cooperative N‐Heterocyclic Carbene/Lewis Acid Catalysis for Highly Stereoselective Annulation Reactions with Homoenolates.

AbstractOptically active cis‐1,3,4‐trisubstituted cyclopentenes are synthesized from enals and chalcone derivatives with high levels of diastereoselectivity and enantioselectivity by the present new method.

Modular Synthesis of 1,2-Diamine Derivatives via Palladium-Catalyzed Aerobic Oxidative Cyclization of Allylic Sulfamides.

Allylic sulfamides undergo efficient aerobic oxidative cyclization at room temperature, mediated by a new Pd catalyst system consisting of 5% Pd(TFA)(2)/10% DMSO in THF. The synthetic utility of these reactions is enhanced by several features: (1) the sulfamide substrates are accessible in multi-gram scale from the corresponding allylic and primary amines, (2) the cyclic sulfamide products are readily converted to the corresponding 1,2-diamines upon treatment with LiAlH(4), and (3) substrates derived from chiral allylic amines cyclize with very high levels of diastereoselectivity.

A double Mannich approach to the synthesis of substituted piperidones—application to the synthesis of substituted E-ring analogues of methyllycaconitine

The double Mannich reaction of acyclic α,γ-substituted β-keto esters and bis(aminol) ethers gives substituted 3,5-substituted-4-piperidones with high levels of diastereoselectivity. These piperdiones can be easily transformed into substituted E-ring analogues of the delphinium alkaloid methyllycacotine.

ChemInform Abstract: Synthesis of Enantiomerically Pure cis-2,4-Disubstituted Piperidines: Extension of Chiral Homoenolate Alkylations Toward the Preparation of Nitrogen Heterocycles.

Abstract Enantiomerically pure cis -2,4-disubstituted piperidines were synthesized from chiral thiolactam 2 in six steps via a highly diastereoselective homoenolate alkylation which set the stereochemistry at the C4 carbon. In addition, two cleavage methods were used to cleave the lactam to the desired piperidines with a high level of diastereoselection at the newly created C2 stereocenter.

ChemInform Abstract: Synthesis and Structure of Condensed Heterocycles Derived from Intramolecular 1,3-Dipolar Cycloaddition of Transient and Enantiomerically Pure α-Allylamino Nitrones and Nitrile Oxides in a High Level of Diastereoselectivity.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Study of a Tandem Aldol-Tischtschenko Reaction Between Chiral Enolsilanes and Aldehydes Catalyzed by Titanium(IV) Isopropoxide.

The synthesis and structure determination of polypropionate is presented. An allyltitanium complex is first used in an allyltitanation reaction; titanium(IV) isopropoxide is next utilized as catalyst in an aldol–Tischtschenko reaction. This method promotes the formation of esters bearing five or six stereocenters in two steps with a very high level of diastereoselectivity and very high yield.

Conjugate addition of lithium N- tert-butyldimethylsilyloxy- N-(α-methylbenzyl)amide: asymmetric synthesis of β 2,2,3-trisubstituted amino acids

Conjugate addition of the homochiral ammonia equivalent lithium N- tert-butyldimethylsilyloxy- N-(α-methylbenzyl)amide to a range of α,β-unsaturated esters gives the corresponding β-amino esters in moderate to good levels of diastereoselectivity. O-Desilylation and cyclisation furnishes homochiral isoxazolidin-5-ones in >99:1 dr after purification. Sequential alkylation of these templates proceeds to give the corresponding 3,4- anti-disubstituted and 3,4,4-trisubstituted derivatives as single diastereoisomers after purification. The first alkylation occurs with high levels of diastereoselectivity on the face of the enolate anti to the C(3)-substituent, whereas the facial selectivity of the second alkylation is governed by a chiral relay effect, which depends upon the relative steric bulk of both the C(3)- and C(4)-substituents. Subsequent hydrogenolysis promotes cleavage of both the N-α-methylbenzyl group and the N–O bond within the isoxazolidin-5-one ring in one pot to give the corresponding β 2,2,3-trisubstituted amino acids directly.

Alkylation and aldol reactions of acyl derivatives of N-1-(1′-naphthyl)ethyl- O- tert-butylhydroxylamine: asymmetric synthesis of α-alkoxy-, α-substituted-β-alkoxy- and α,β-dialkoxyaldehydes

Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1′-naphthyl)ethyl- O- tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates α-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1′-naphthyl)ethyl- O- tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH 4 to give enantiopure α-alkoxy-, α-substituted-β-alkoxy- and α,β-dialkoxyaldehydes in good yield.

Cooperative N-Heterocyclic Carbene/Lewis Acid Catalysis for Highly Stereoselective Annulation Reactions with Homoenolates

A new approach that takes advantage of N-heterocyclic carbene/Lewis acid cooperative catalysis provides access to cis-1,3,4-trisubstituted cyclopentenes from enals and chalcone derivatives with high levels of diastereoselectivity and enantioselectivity. The presence of Ti(OiPr)(4) as the Lewis acid allows for efficient substrate preorganization, which translates into high levels of diastereoselectivity. Additionally, we demonstrate the possibility of controlling the absolute stereochemistry of NHC-catalyzed reactions by employing a catalytic amount of a chiral Lewis acid as the unique source of optically active promoter.

Enantiospecific Stereodivergent Synthesis of trans‐ and cis‐N(2),3‐Dimethyl‐4‐phenyl‐1,2,3,4‐tetrahydroisoquinolines

The acid-promoted cyclizations of a range of N-benzylethanolamines (derived from pseudoephedrine or ephedrine) give the corresponding trans-N(2),3-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolines with high levels of diastereoselectivity and in good yields of isolated product. The cyclizations of the corresponding chromium tricarbonyl complexes are rendered completely stereoselective. Acid-promoted cyclization of N-(3',4'-dimethoxybenzyl)ephedrine and its chromium tricarbonyl complex occur with complementary diastereoselectivities to give trans- and cis-N(2),3-dimethyl-4-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline, respectively, in >99:1 d.r. The latter is consistent with a "double inversion" mechanism, which involves neighboring group participation by the chromium tricarbonyl moiety followed by rearomatization to give the corresponding cis-tetrahydroisoquinoline with overall retention of configuration.