Diastereoselective Reaction Research Articles

Diastereo- and enantioselective preparation of cyclopropanol derivatives.

The diastereoselective carbocupration reaction of alkoxy-functionalized cyclopropene derivatives, followed by a subsequent trapping of the resulting cyclopropylmetal species with an electrophilic source of oxygen (oxenoid) afforded various tetrasubstituted cyclopropanol derivatives in high diastereo- and enantiomeric ratios. Similarly, the enantioselective copper-catalyzed carbomagnesiation/oxidation (or amination) sequence on achiral nonfunctionalized cyclopropenes provided the desired cyclopropanol (and cyclopropylamine) derivatives in excellent diastereo- and enantiomeric excesses.

Forming Benzylic Iodides via a Nickel Catalyzed Diastereoselective Dearomative Carboiodination Reaction of Indoles

AbstractA diastereoselective dearomative carboiodination reaction is reported. We report a novel metal‐catalyzed approach to install reactive secondary benzylic iodides. Utilizing the unique reactivity of nickel, we have expanded the carboiodination reaction to non‐activated aromatic double bonds forming a previously unattainable class of iodides. We also report a broadly applicable method to avoid the use of a metallic reducing agent by utilizing an alkyl phosphite as the ligand. The reaction is thought to proceed through a syn intramolecular carbonickelation across a 2‐substituted indole followed by a diastereoretentive reductive elimination of the carbon−iodine bond. The complex iodinated indolines generated in the reaction were obtained in moderate to good yields and good to excellent diastereoselectivity. The products were easily functionalized by a variety of synthetic methods.

Forming Benzylic Iodides via a Nickel Catalyzed Diastereoselective Dearomative Carboiodination Reaction of Indoles.

A diastereoselective dearomative carboiodination reaction is reported. We report a novel metal-catalyzed approach to install reactive secondary benzylic iodides. Utilizing the unique reactivity of nickel, we have expanded the carboiodination reaction to non-activated aromatic double bonds forming a previously unattainable class of iodides. We also report a broadly applicable method to avoid the use of a metallic reducing agent by utilizing an alkyl phosphite as the ligand. The reaction is thought to proceed through a syn intramolecular carbonickelation across a 2-substituted indole followed by a diastereoretentive reductive elimination of the carbon-iodine bond. The complex iodinated indolines generated in the reaction were obtained in moderate to good yields and good to excellent diastereoselectivity. The products were easily functionalized by a variety of synthetic methods.

Neighboring Hydroxyl Group-Assisted Allylboration and Lewis Acid-Mediated Carbonyl-Ene Reaction for Access to a Hapalindole Cyclohexane Core with Multiple Contiguous Stereogenic Centers.

A neighboring hydroxyl group-assisted allylboration of 3-indolyl ketones with γ,γ-disubstituted allylboronic acids is reported, affording various 3-indolyl-substituted homoallylic alcohols in good yields with excellent diastereoselectivies (up to >20:1 dr). The hydroxyl group not only played a vital role in the challenging allylboration but was elaborated for the subsequent construction of a hapalindole cyclohexane core by a highly diastereoselective Lewis acid-catalyzed carbonyl-ene reaction. In the overall process, four contiguous stereogenic centers including two quaternary stereogenic centers were installed.

Convenient diastereoselective synthesis of annulated 3-substituted-(5S*,6S*,Z)-2-(2-(2,4-dinitrophenyl)hydrazono)-5,6-diphenyl-1,3-thiazinan-4-ones

Racemic 2-(2,4-dinitrophenyl)hydrazono)-5,6-diphenyl-1,3-thiazinan-4-ones and (Z)-N'-(2,4-dinitrophenyl)-2,3-diphenylacrylohydrazide were formed during the diastereoselective reaction between 4-substituted 1-(2,4-dinitrophenyl)thiosemicarbazides and 2,3-diphenylcycloprop-2-enone under refluxing ethanol. The structures of the synthesized compounds were confirmed by single-crystal X-ray analyses.

Network topology and cavity confinement-controlled diastereoselectivity in cyclopropanation reactions catalyzed by porphyrin-based MOFs

In this work, we show that the stereoselectivity of a reaction can be controlled by directing groups of substrates, by network topology and by local cavity confinement of metal–organic framework (MOF) catalysts.

SA116Open Board

Cinchona-based chiral hyperbranched polymers (HBPs) were designed and successfully synthesized via the Mizoroki-Heck (MH) coupling reaction. AB2 and A2B-type chiral monomers were prepared from cinchona squaramide derivatives, where A (vinyl) reacted only with B (iodophenyl) under MH reaction conditions. The chiral HBPs obtained by the MH polymerization contained cinchona squaramide moieties and demonstrated excellent diastereoselectivity and enantioselectivity in asymmetric Michael addition reactions of methyl 2-oxocyclopentanecarboxylate and trans-β-nitrostyrene. These newly designed HBPs were structurally robust and could be reused for further reaction without losing their catalytic activity.

Tungsten anchored onto functionalized SBA-15: an efficient catalyst for diastereoselective synthesis of 2-azapyrrolizidine alkaloid scaffolds.

We used a novel hybrid catalyst in chemo-, regio-, and diastereoselective multi-component reactions (MCR) for the synthesis of the 2-aza analogue of pyrrolizidine and spirooxindole-2-azapyrrolizidine derivatives. The nanocatalyst, W(iv)/NNBIA–SBA-15 [where NNBIA = N,N′-(ethane-1,2-diyl)bis(2-aminobenzamide)] was synthesized by covalent grafting on chloro-functionalized SBA-15. The synthesis process was followed by the anchoring of WCl6 to catch the desired catalyst. The quality of the catalyst was assessed using different analytical techniques such as X-ray diffraction spectroscopy (XRD), Fourier-transform infrared spectroscopy (FT-IR), N2 adsorption analysis, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), ammonia Temperature Programmed Desorption (TPD), X-Ray photoelectron spectroscopy (XPS) and thermogravimetric, differential thermal analysis (TGA-DTA). The catalyst, W(iv)/NNBIA–SBA-15, with high catalytic performance is a good candidate for the diastereoselective synthesis of 2-azapyrrolizidine alkaloid scaffolds. The catalyst could be recovered for reuse without noticeable loss of activity.

Recent advances in the asymmetric synthesis of pharmacology-relevant nitrogen heterocycles via stereoselective aza-Michael reactions.

The prevalence of nitrogen containing heterocycles in natural products and pharmaceuticals is a doubtless fact. In this review, recent applications of a stereoselective aza-Michael reaction as an efficient tool for the asymmetric synthesis of naturally occurring nitrogen-containing heterocyclic scaffolds and their usefulness to pharmacology are reviewed and summarized. The available data are for the first time classified according to types of heterocyclic products and subdivided in accordance with synthetic methodologies used as key stereocontrolling steps (diastereoselective or enantioselective reactions, single bond-forming or cascade reactions, etc.). This classification is convenient for organic chemists and for researchers working in the areas of natural product synthesis and medicinal chemistry. Specific attention is paid to organocatalytic asymmetric versions of the aza-Michael reaction developed over the past decade.

Cu-Catalyzed highly selective reductive functionalization of 1,3-diene using H2O as a stoichiometric hydrogen atom donor.

A copper-catalyzed highly regio- and diastereo-selective reductive reaction of terminal 1,3-diene with water and aldehyde has been developed. This chemistry afforded a product containing a terminal alkenyl group, which is a versatile kind of precursor for organic synthesis, with the scope for various substrates. The present reaction system could realize the catalytic transfer of hydrogen to diene using water as a stoichiometric H atom donor. In this transformation, B2Pin2, a mild and practical kind of reductant was used as the mediator. The reaction pathway of this practical strategy was illustrated by a control experiment.

Total syntheses of several iridolactones and the putative structure of noriridoid scholarein A: an intramolecular Pauson-Khand reaction based one-stop synthetic solution.

A simple and general approach towards the total syntheses of several iridolactones such as (±)-boschnialactone, (±)-7-epi-boschnialactone, (±)-teucriumlactone, (±)-iridomyrmecin, (±)-isoboonein, (±)-7-epi-argyol, (±)-scabrol A, (±)-7-epi-scabrol A, and (±)-patriscabrol as well as the putative structure of scholarein A is delineated. The synthetic strategy features a diastereoselective intramolecular Pauson-Khand reaction (IPKR) to construct the iridoid framework followed by some strategic synthetic manipulations to access the targeted monoterpenes including those having diverse oxy-functionalization patterns and with 3-5 contiguous stereogenic centres in a highly stereocontrolled manner. Also, the present endeavour includes the first total synthesis of scabrol A.

Diastereoselective vinylogous Mannich reaction of perfluoroalkylated cyclic imines with 2-trimethylsilyloxyfuran

The reaction between 2-trimethylsilyloxyfuran and perfluoroalkylated cyclic ketimines with different ring sizes affords 5-(2-perfluoroalkyl-1-azacycloalk-2-yl)furan-2(5H)-ones in yields up to 89% and with excellent rel-(R,R)-diastereoselectivity.

Highly diastereoselective synthesis of enantioenriched anti-α-allyl-β-fluoroamines.

A highly diastereoselective synthesis of anti-α-allyl-β-fluoroamines has been developed involving enantioselective α-fluorination of aldehydes followed by a diastereoselective Petasis allyl borono-Mannich reaction. The products are obtained generally in good overall yields for the two steps and with drs of 97 : 3-99 : 1 and ees of 86-92%. Selected products were converted to 3-, 5- and 6-membered ring heterocycles, the latter two types incorporating an exo-cyclic fluorine.

A copper-catalyzed diastereoselective O-transfer reaction of N-vinyl-α,β-unsaturated nitrones with ketenes into γ-lactones through [5 + 2] cycloaddition and N–O bond cleavage

A copper-catalyzed atom economical O-transfer reaction strategy was developed for the synthesis of densely functionalized γ-lactones from N-vinyl-α,β-unsaturated nitrones and ketenes.

Copper-catalyzed highly diastereoselective cross-dehydrogenative coupling between 8-hydroxyisochromanes and 1,3-dicarbonyl compounds

A novel copper-catalyzed highly diastereoselective cross-dehydrogenative coupling reaction for the access of tricyclic chromanes from 8-hydroxyisochromanes and 1,3-dicarbonyl compounds.

Iron-mediated highly diastereoselective allylation of carbonyl compounds with cyclic allylic halides

An efficient iron-mediated highly diastereoselective allylation reaction of carbonyl compounds with cyclic allylic halides using a catalytic amount of bismuth(iii) chloride is reported.

Acetylene-based two-step diastereoselective synthesis of bridgehead dihydro-oxadiazines using ketones and hydrazine as the only reactants.

Pharmaceutically related bridgehead dihydro-1,3,4-oxadiazines are synthesized in up to 94% yield by the acid-catalyzed diastereoselective reaction of hydrazine hydrate with 6,8-dioxabicyclo[3.2.1]octanes (6,8-DOBCOs), the products of the superbase-promoted self-organization of acetylene with ketones. The synthesis covers a diverse range of alkylaromatic ketones having F-, Cl-, Br-, alkoxy-, CF3- and aryl substituents in different positions of the aromatic rings.

In(OTf)3-Catalyzed Cascade Cyclization for Construction of Oxatricyclic Compounds.

A highly diastereoselective cascade cyclization reaction has been developed for establishing a series of oxatricyclic compounds using Chan's diene and simple keto alkynal substrates with only 1 mol % of In(OTf)3 as the catalyst in 82-92% yields. The potential utility of this synthetic strategy has been demonstrated in model studies for the construction the core structures of 1α,8α:4α,5α-diepoxy-4,5-dihydroosmitopsin and cortistatin A.

Metal- and Hydride-Free Pentannulative Reductive Aldol Reaction.

Traditionally, the reductive aldol reaction is a metal-catalyzed and hydride-promoted coupling between enones and aldehydes. We present a phosphine-mediated diastereoselective intramolecular reductive aldol reaction of α-substituted dienones and aldehydes, which is metal-free and hydride-free. The synthetic utility of the reductive aldol adducts is demonstrated by elaborating them in one step to indeno[1,2- b]furanones, indeno[1,2- b]pyrans, and dibenzo[ a, h]azulen-8-ones.

Direct Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Esters/Lactones via Umpolung Strategy.

Enabled by the discovery of new cinchonium salts and coadditives, a direct and efficient asymmetric access to trifluoromethylated γ-amino esters/lactones has been realized through the enantioselective and diastereoselective umpolung reaction of trifluoromethyl imines with acrylates or α,β-unsaturated lactones as carbon electrophiles. At 0.5-5.0 mol % catalyst loadings, the newly developed catalytic system activates a variety of imine substrates as unconventional nucleophiles to mediate highly chemo-, regio-, diastereo-, and enantioselective C-C bond forming reactions. The developed synthetic protocol represents an excellent strategy to target a series of versatile and enantiomerically enriched γ-amino esters/lactones in good to excellent yields from the readily available starting materials. Additionally, we found that the epi-vinyl catalysts based on cinchonidine and quinine promote a similarly high enantioselective reaction generating the opposite configuration of chiral products in a highly efficient manner, which allows convenient access to either the R- or S-enantiomer of the chiral amine products in high yields and excellent enantioselectivities.