Heteroatom‐Guided,Palladium‐Catalyzed,Site‐Selective CH Arylation of 4H‐Chromenes: Diastereoselective Assembly of the Core Structure of Myristinin B through Dual CH Functionalization

A highly site‐selective, heteroatom‐guided, palladium‐catalyzed direct arylation of 4H‐chromenes is reported. The C?H functionalization is driven not only by the substituents and structure of the substrate but also by the coupling partner being used. The diastereoselective assembly of the core structure of Myristinin B has been achieved by using a dual C?H functionalization strategy for regioselective direct arylation.     

Unprecedented Diastereoselective Arylogous Michael Addition of Unactivated Phthalides

The first highly enantioselective arylogous Michael reaction (AMR) of 3-unsubstituted phthalides has been described. This phase-transfer methodology, which uses catalytic amounts of KOH/18-crown-6 catalyst in mesitylene in the presence of N,O-bis(trimethylsilyl)acetamide (BSA), gives access to a broad range of 3-monosubstituted phthalides with high levels of syn diastereoselectivity and good yields, starting from 3-unsubstituted derivatives and diverse α,β-unsaturated carbonyl compounds. The reaction also applies to unactivated 3-alkyl phthalides to afford 3,3-dialkyl derivatives. A plausible mechanism has been suggested. DFT analysis of possible transition states gives a rationale of the high syn diastereoselectivity observed and its correlation with the solvent's dielectric constant.     

Diastereoselective Cyclobutenol Synthesis: A Heterogeneous Palladium-Catalyzed Oxidative Carbocyclization-Borylation of Enallenols

A highly selective and efficient oxidative carbocyclization/borylation of enallenols catalyzed by palladium immobilized on amino-functionalized siliceous mesocellular foam (Pd-AmP-MCF) was developed for diastereoselective cyclobutenol synthesis. The heterogeneous palladium catalyst can be recovered and recycled without any observed loss of activity or selectivity. The high diastereoselectivity of the reaction is proposed to originate from a directing effect of the enallenol hydroxyl group. Optically pure cyclobutenol synthesis was achieved by the heterogeneous strategy by using chiral enallenol obtained from kinetic resolution.     

Which Stereoinductor Is Better for Asymmetric Functionalization of α-Amino Acids in a Nickel(II) Coordination Environment? Experimental and DFT Considerations

The results of extended comparative investigation of nickel(II) Schiff base complexes (containing various auxiliary chiral moieties) commonly used as a methodological platform for the asymmetric synthesis of tailor-made α-amino acids are provided. The following issues are addressed: 1) redox activity (determining the possibility for electrochemically induced reactions); 2) quantitative estimation of the reactivity of deprotonated complexes towards electrophiles; and 3) quantum-chemical estimation of noncovalent interactions in the metal coordination environment (which shed light on the origin of the stereochemical outcome observed for different stereoinductors). Possible mechanisms that determine the relationship between the stereochemical configuration of a molecule and its electronic structure are discussed. The DFT-calculated HOMO–LUMO energies and localization, as well as relative energies for the (S)- and (R)-alanine derivatives, that determine the stereoinduction efficiency in thermodynamically controlled reactions in nickel(II) coordination are provided. The computational data are supported by experimental results on the monobenzylation of glycine derivatives.     

Enantioselective Catalytic [4+1]-Cyclization of ortho-Hydroxy-para-Quinone Methides with Allenoates

The first highly asymmetric catalytic synthesis of densely functionalized dihydrobenzofurans is reported, which starts from ortho-hydroxy-containing para-quinone methides. The reaction relies on an unprecedented formal [4+1]-annulation of these quinone methides with allenoates in the presence of a commercially available chiral phosphine catalyst. The chiral dihydrobenzofurans were obtained as single diastereomers in yields up to 90 % and with enantiomeric ratios up to 95:5.     

Highly Diastereoselective Synthesis of Methylenecyclobutanes by Merging Boron‐Homologation and Boron‐Allylation Strategies

A highly diastereoselective synthesis of methylenecyclobutanes possessing a quaternary stereocenter is reported, in which boron homologation of an easily‐generated cyclobutenylmetal species is performed, followed by an allylation reaction. Combining three steps in a one‐pot process further optimized the method, which afforded the expected adducts in excellent yields and stereoselectivity, starting from commercially available 4‐bromobutyne.     

Four oxoindole‐linked α‐alkoxy‐β‐amino acid derivatives

Four structures of oxoindolyl α‐hydroxy‐β‐amino acid derivatives, namely, methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐methoxy‐2‐phenylacetate, C₂₄H₂₈N₂O₆, (I), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐ethoxy‐2‐phenylacetate, C₂₅H₃₀N₂O₆, (II), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐[(4‐methoxybenzyl)oxy]‐2‐phenylacetate, C₃₁H₃₄N₂O₇, (III), and methyl 2‐[(anthracen‐9‐yl)methoxy]‐2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐phenylacetate, C₃₈H₃₆N₂O₆, (IV), have been determined. The diastereoselectivity of the chemical reaction involving α‐diazoesters and isatin imines in the presence of benzyl alcohol is confirmed through the relative configuration of the two stereogenic centres. In esters (I) and (III), the amide group adopts an anti conformation, whereas the conformation is syn in esters (II) and (IV). Nevertheless, the amide group forms intramolecular N—H...O hydrogen bonds with the ester and ether O atoms in all four structures. The ether‐linked substituents are in the extended conformation in all four structures. Ester (II) is dominated by intermolecular N—H...O hydrogen‐bond interactions. In contrast, the remaining three structures are sustained by C—H...O hydrogen‐bond interactions.     

Brønsted Acid Catalysis in Visible‐Light‐Induced [2+2] Photocycloaddition Reactions of Enone Dithianes

1,3‐Dithiane‐protected enones (enone dithianes) were found to undergo an intramolecular [2+2] photocycloaddition under visible‐light irradiation (λ =405 nm) in the presence of a Brønsted acid (7.5–10 mol %). Key to the success of the reaction is presumably the formation of colored thionium ions, which are intermediates of the catalytic cycle. Cyclobutanes were thus obtained in very good yields (78–90 %). It is also shown that the dithiane moiety can be reductively or oxidatively removed without affecting the photochemically constructed ring skeleton.     

β-N-Heterocyclic Cyclobutane Carboximides: Synthesis through a Tandem Base-Catalyzed Amidation/aza-Michael Addition Protocol and Facile Transformations

A stereoselective one-pot double derivatization of cyclobutene-1-carboxylic acid via a mild organic base catalyzed amidation/aza-Michael addition of benzo[d]oxazol-2(3H)-ones has been developed. This unprecedented tandem reaction provides access to novel β-N-heterocyclic cyclobutane carboximide derivatives with a trans geometry. The carboximide moiety reacts smoothly with nucleophiles, allowing access to diverse derivatives of trans-β-N-heterocyclic cyclobutanecarboxylic acid, including peptidomimetic structures.     

Highly Diastereo‐ and Enantioselective Michael Addition of Nitroalkanes to 2‐Enoyl‐Pyridine N‐Oxides Catalyzed by Scandium(III)/Copper(II) Complexes

A C₂‐symmetric Schiff‐base ligand, derived from tridentate‐Schiff‐base, was developed and successfully applied to the asymmetric Michael addition of nitroalkanes to 2‐enoyl‐pyridine N‐oxides. With this newly catalytic system, an unprecedented diastereoselectivity was obtained in the asymmetric Michael addition of nitroalkanes to 2‐enoyl‐pyridine N‐oxides. In addition, a switch in enantioselectivity was achieved by using this newly catalytic system and our previous catalyst. After a facile reduction, the optically active adduct was converted to a biologically active dihydro‐2H‐pyrrol 4 a . Furthermore, a connection of two tridentate‐Schiff‐base subunits proved to be an effective strategy in ligand design.