Diastereoselective Ring Opening Research Articles

Mono- and bis(steroids) containing a cyclooctane core: Synthesis, antiproliferative activity, and action on cell cytoskeleton microtubules.

Steroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring-opening of mono- and polyoxiranes, containing a cyclooctane core, by azide-anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper-catalyzed azyde-alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.

Palladium-catalyzed stereocontrolled ring-opening of 7-oxabenzonorbornadienes with organic carboxylic acids.

A palladium-catalyzed tandem reaction of 7-oxabenzonorbornadienes with organic carboxylic acids that provides cis-1,2-dihydro-l-naphthyl derivatives in moderate to good yields in a highly diastereoselective manner is described. A possible reaction mechanism involving syn acylation followed by insertion and diastereoselective ring-opening with 7-oxabenzonorbornadienes is proposed to account for the reaction.

Lewis acid-catalyzed diastereoselective carbofunctionalization of bicyclobutanes employing naphthols.

Traditional radical-mediated ring-opening of bicyclo[1.1.0]butanes (BCBs) for cyclobutane synthesis suffers from poor diastereoselectivity. Although few reports on BCB ring-opening via polar mechanisms are available, the Lewis acid-catalyzed diastereoselective ring-opening of BCBs using carbon nucleophiles is still underdeveloped. Herein, we report a mild and diastereoselective Bi(OTf)3-catalyzed ring-opening of BCBs employing 2-naphthols. The anticipated carbofunctionalized trisubstituted cyclobutanes were obtained via a bicoordinated bismuth complex and the products are formed in good to excellent yields with high regio- and diastereoselectivity. The scope of the reaction was further extended using electron-rich phenols and naphthylamine. The functionalization of the synthesized trisubstituted cyclobutanes shows the synthetic utility of the present method.

Catalytic Asymmetric Chlorination of Isoxazolinones

AbstractOrganic compounds featuring a chlorine substituted stereocenter are frequently found in nature and are interesting for pharmaceutical applications and as synthetic building blocks. Catalytic methods to generate such stereocenters by C,H bond functionalization are still relatively rare. Here we report the first catalytic asymmetric chlorination of isoxazolinones, a synthetically and biologically interesting class of heterocycles, which can be considered as precursors for β‐aminoacids. The title reaction was catalyzed with high enantioselectivity by a planar chiral ferrocene based palladacycle in high to excellent yields. It is showcased that the products are valuable for post‐synthetic transformations. An SN2 reaction proceeded with smooth inversion of the absolute configuration. The substitution product could then be transformed into an α‐azido β‐aminoacid derivative via a reductive, diastereoselective ring opening.

Diastereoselective ring opening of fully-substituted cyclopropanes via intramolecular Friedel–Crafts alkylation

Diastereoselective ring opening of fully-substituted cyclopropanes via intramolecular Friedel–Crafts alkylation

Diastereoselective ring opening of fully-substituted cyclopropanes via intramolecular Friedel-Crafts alkylation.

We herein disclose a diastereoselective ring opening of non-donor-acceptor cyclopropanes via an intramolecular Friedel-Crafts alkylation en route to functionalized dihydronaphthalene scaffolds possessing quaternary carbon stereocentres. The transformation proceeds through a selective bond breaking at the most alkylated carbon centre with a pure retention of configuration. Mechanistic investigations and computational studies revealed that alkoxy functionality is the key for selective bond breaking leading to a complete retention of configuration.

Total Synthesis of C30 Botryococcene and epi‐Botryococcene by a Diastereoselective Ring Opening of Alkenylcyclopropanes

AbstractTrialkylaluminum compounds perform a diastereoselective 1,6‐ring fragmentation of alkenylcyclopropane. This new tool allows the preparation of hydrocarbon compounds containing two distant stereocenters with a good diastereocontrol. Inspired by the biosynthesis of botryococcene this methodology was applied successfully to the diastereo‐ and enantioselective preparation of this triterpene and its epimer.

Total Synthesis of C30 Botryococcene and epi-Botryococcene by a Diastereoselective Ring Opening of Alkenylcyclopropanes.

Trialkylaluminum compounds perform a diastereoselective 1,6-ring fragmentation of alkenylcyclopropane. This new tool allows the preparation of hydrocarbon compounds containing two distant stereocenters with a good diastereocontrol. Inspired by the biosynthesis of botryococcene this methodology was applied successfully to the diastereo- and enantioselective preparation of this triterpene and its epimer.

Visible-Light Promoted Distereodivergent Intramolecular Oxyamidation of Alkenes.

The visible-light-promoted diastereodivergent intramolecular oxyamination of alkenes is described to construct oxazolindinones, pyrrolidinones and imidazolidones via mild generation of primary amidyl radicals from functionalized hydroxylamines. A unique phenomenon of highly diastereoselective ring-opening of aziridines controlled by electron sacrifices was observed. Highly diastereoselective amino alcohols derivatives were obtained efficiently through this protocol in gram scales. The mechanistic studies suggested the isolatable anti-aziridine intermediates were generated quickly from primary amidyl radicals and the diastereoselectivities were controlled by pKa values of the electron sacrifices.

Efficient and Easy Access to Optically Pure Tetrasubstituted Tetra­hydrofurans via Stereoselective Opening of C2‐Symmetric Epoxide and Aziridine Rings

AbstractAn efficient and facile protocol to functionalize position C‐3 of 2,5‐anhydro‐D‐mannitol via diastereoselective ring opening of a C2‐symmetric epoxide 2,5:3,4‐dianhydro‐D‐allitol 3 has been developed. This method is protecting‐group‐free, high‐yielding, and provides access to C‐3‐modified 2,5‐anhydro‐D‐mannitols 5a, 11a–15a and 16–17. This method was then extrapolated to the synthesis of a C2‐symmetric aziridine, which underwent ring opening with various nucleophiles to provide access to C‐3‐ and C‐4‐modified 2,5‐anhydro‐D‐mannitols 19–27 in excellent global yields and moderate to good diastereoselectivities. These structures and their derivatives are potentially useful in a variety of applications, including organocatalysis of asymmetric Michael additions as demonstrated with diamine monosulfonamides 28a and 28b, which provide adducts with complementary enantioselectivity.

Experimental and theoretical investigations of the stereoselective synthesis of p-stereogenic phosphine oxides.

An efficient enantioselective strategy for the synthesis of variously substituted phosphine oxides has been developed, incorporating the use of (1S,2S)-2-aminocyclohexanol as the chiral auxiliary. The method relies on three key steps: 1) Highly diastereoselective formation of P(V) oxazaphospholidine, rationalized by a theoretical study; 2) highly diastereoselective ring-opening of the oxazaphospholidine oxide with organometallic reagents that takes place with inversion of configuration at the P atom; 3) enantioselective synthesis of phosphine oxides by cleavage of the remaining P-O bond. Interestingly, the use of a P(III) phosphine precursor afforded a P-epimer oxazaphospholidine. Hence, the two enantiomeric phosphine oxides can be synthesized starting from either a P(V) or a P(III) phosphine precursor, which constitutes a clear advantage for the stereoselective synthesis of sterically hindered phosphine oxides.

Enantioselective Formal Synthesis of (−)-Podophyllotoxin from (2S,3R)-3-Arylaziridine-2-carboxylate

Meyers' 4-aryl-1-tetralone-lactone and ent-Zhang's 2-diarylmethyl-4-oxobutanoate were synthesized in the formal synthesis of (-)-podophyllotoxin from (2S,3R)-3-arylaziridine-2-carboxylate, via 3,3-diarylpropanoate as a common intermediate, in an overall 42% yield through 10 steps and 31% yield through 6 steps, respectively. The key steps in the synthesis were regio- and diastereoselective ring opening with an aromatic nucleophile, samarium iodide promoted reductive C-N bond cleavage, and Stille coupling for introducing the vinyl functionality. The starting aziridine was enantioselectively prepared from 3,4,5-trimethoxybenzaldehyde by guanidinium ylide mediated asymmetric aziridination. All nitrogen components used in the reaction sequence are reusable as the starting guanidinium source.

Carbon-based solid acid: an efficient and reusable catalyst for the diastereoselective ring opening reaction of α-epoxyketones

Carbon-based solid acid efficiently catalyzes diastereoselective ring opening of α-epoxyketones in the presence of methanol to produce the corresponding α-hydroxy-β-methoxyketones in excellent yield.

Synthesis of β-Fluoroamines by Lewis Base Catalyzed Hydrofluorination of Aziridines

Lewis base catalysis promotes the in situ generation of amine-HF reagents from benzoyl fluoride and a non-nucleophilic alcohol. The hydrofluorination of aziridines to provide β-fluoroamines using this latent HF source is described. This protocol displays a broad scope with respect to aziridine substitution and N-protecting groups. Examples of regio- and diastereoselective ring opening to access medicinally relevant β-fluoroamine building blocks are presented.

Highly Facialselective Synthesis of Pyranose 1,3-Oxazines and Their Ring Opening with Nucleophiles: A Novel Entry to 2-C-Branched Glycosides

A TMSOTf-promoted cycloaddition of N-benzoyl-N,O-acetals with various glycals and 3-deoxy glycals affords pyranose 1,3-oxazines with high facial selectivity. In addition, a highly diastereoselective ring opening of the resulting pyranose 1,3-oxazines is reported. With diverse nucleophiles, these reactions take place upon heating at 80 °C. This novel ring-opening reaction affords structurally diversified 2-C-branched glycosides with three newly formed contiguous stereocenters.

A Synthetic Route to Highly Substituted 1,2,3,4‐Tetrahydroisoquinolines via Yb(OTf)3‐Catalyzed Diastereoselective Ring Opening of Bridged Oxazolidines: Asymmetric Synthesis of 2‐Azapodophyllotoxin

We herein report a robust and efficient synthetic route to highly functionalized enantiopure 1,2,3,4-tetrahydroisoquinolines (THIQs) from Garner aldehyde. We utilized the inherent chirality of Garner aldehyde through 1,2- and 1,3-/1,4-asymmetric inductions iteratively to obtain 1,2,3,4-tetrasubstitued THIQs using rigid and isolable bridged oxazolidines without any external chiral sources. All possible stereoisomers of bridged oxazoliodines were efficiently synthesized from L- and D-Garner aldehydes and transformed into fully functionalized THIQs via diastereoselective ring opening with various nucleophiles in the presence of Yb(OTf)(3). This methodology furnished four out of eight possible diastereomers of 1,2,3,4-tetrasubstituted THIQs despite the electronic nature of substituents on the aryl rings. Finally, the enantioselective synthesis of 2-azapodophyllotoxin was achieved with an overall yield of 35.4% (eight steps) from D-Garner aldehyde using this synthetic route.

Diastereoselective reactions of 1,1,1-trichloro(trifluoro)-3-nitrobut-2-enes with 2-morpholinoalk-1-enes

Reactions of (E)-1,1,1-trichloro(trifluoro)-3-nitrobut-2-enes with 3,3-dimethyl-2-morpholinobutene in benzene give (4R*,6R*)6-tert-butyl-3-methyl-6-morpholino-4-trihalomethyl-5,6-dihydro-4H-1,2-oxazine 2-oxides. In a dichloromethane solution, these cyclic nitronates undergo diastereoselective ring opening to produce nitroalkylated anti-CCl3- and syn-CF3-enamines, which are hydrolysed with dilute HCl to afford the respective anti-CCl3- and syn-CF3-g-nitroketones.

ChemInform Abstract: Diastereoselective Ring Opening of 2-Substituted N-Benzyl-4,4,7α- trimethyl-trans-octahydro-1,3-benzoxazines by Grignard Reagents. Highly Enantioselective Synthesis of Primary Amines.

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: Novel Concepts in Directed Biaryl Synthesis. Part 4. Diastereoselective Ring Opening of Achiral Bridged Biaryls Using Chiral O- and N-Nucleophiles: First Atropo-Enantioselective Synthesis of (-)-4,4′-Bis(orcinol).

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: A New Diastereoselective Synthesis of a 1β-Methylcarbapenem Intermediate.

A 1β-methylcarbapenem key intermediate is synthesized from methyl (R)-3-hydroxybutyrate via the diastereoselective alkylation and regioselective cuprate ring opening of a chiral epoxide which is readily prepared from Sharpless asymmetric epoxidation of the corresponding allylic alcohol.