Aryl Nucleophiles Research Articles

A Sc(OTf)3 catalyzed dehydrogenative reaction of electron-rich (hetero)aryl nucleophiles with 9-aryl-fluoren-9-ols.

A highly efficient dehydrogenative reaction of a series of nucleophiles with 9-aryl-fluoren-9-ols has been realized by using only 2 mol% of Sc(OTf)3 as a catalyst. The corresponding indole-containing 9,9-diarylfluorenes were obtained in up to 99% yield as well as other electron-rich (hetero)arene adducts. The protocol exhibits high selectivity, mild reaction conditions and good substrate compatibility (32 examples). This protocol is further highlighted by its applications in the construction of potential electroluminescent materials.

Lewis-Acid-Mediated Union of Epoxy-Carvone Diastereomers with Anisole Derivatives: Mechanistic Insight and Application to the Synthesis of Non-natural CBD Analogues.

The use of trimethylsilyl trifluoromethanesulfonate as a mild means to unite epoxy-carvone silyl ethers with anisole derivatives to yield products that are structurally similar to the CBD scaffold is reported. Importantly, unlike related methods, this process can utilize both epoxy-carvone diastereomers and does not require the use of air/moisture-sensitive organometallic reagents. Several examples of aryl nucleophiles as well as mechanistic insight based on in silico computational analysis are presented.

Ketone C–C Bond Activation Meets the Suzuki-Miyaura Cross-coupling

In a recent issue of the Journal of the American Chemical Society, Dong and coworkers report that ketones can participate as electrophiles in the Suzuki-Miyaura cross-coupling reaction under Rh(I) catalysis. They show that activation of C–C bonds of unstrained ketones is a versatile process that can engage in cross-coupling reaction with aryl boronates.

Carboxylate-Directed Addition of Aromatic C–H Bond to Aromatic Aldehydes under Ruthenium Catalysis

We report that ruthenium complexes effectively catalyzed the carboxylate-directed addition of aromatic C–H bonds to aldehydes. The reactions of aromatic acids with a variety of aromatic aldehydes including unactivated ones proceeded efficiently to give the corresponding isobenzofuranone derivatives in high yields. The combination of ruthenium(II) complexes with tricyclohexylphosphine led to highly nucleophilic aryl–metal species, which enabled versatile [3 + 2] cycloaddition in the absence of a Lewis acid. This paper also demonstrates the application of supported ruthenium catalysts to the title reaction.

Acid-catalyzed oxidative cleavage of S–S and Se–Se bonds with DEAD: efficient access to sulfides and selenides

An acid/DEAD system for oxidative cleavage of S–S and Se–Se bonds to generate chalcogenium ions has been developed. These ions could be captured by nucleophile-tethered alkenes and nucleophilic aryl reagents such as arylboronic acids and arenes to give chalcogenides.

Tertiary and Quaternary Carbon Formation via Gallium-Catalyzed Nucleophilic Addition of Organoboronates to Cyclopropanes

GaCl3 and (IPr)GaCl3/AgSbF6 formed γ-tertiary and γ-quaternary carbons via homoconjugate addition of organoboron nucleophiles to diester- and ketone-functionalized cyclopropanes. Electron donor group cyclopropane substituents were not needed, allowing electron-deficient aryl, alkenyl, alkyl, and hydrogen-substituted cyclopropanes to be used. The catalytic conditions were compatible with alkenyl, alkynyl, and aryl nucleophiles, including ortho-substituted aromatics, to synthesize highly hindered quaternary carbons. Alkynyl nucleophiles formed substituted cyclopentenes. A control experiment supports an intermediate carbocation in quaternary carbon center formation.

Nucleophilic Arylation of N,O-Ketene Acetals with Triaryl Aluminum Reagents: Access to α-Aryl Amides through an Umpolung Process.

A novel approach for the umpolung α-arylation of amides is presented. By the nucleophilic phenylation of O-silyl N,O-ketene acetals, generated in situ from N-alkoxy amides, a phenyl group can be introduced onto the α-carbon atom of amides through N-O bond cleavage in a two-step, one-pot process. The asymmetric synthesis of α-aryl amides through the diastereoselective arylation of a chiral N,O-ketene acetal is also described.

Nucleophilic Arylation of N,O‐Ketene Acetals with Triaryl Aluminum Reagents: Access to α‐Aryl Amides through an Umpolung Process

AbstractA novel approach for the umpolung α‐arylation of amides is presented. By the nucleophilic phenylation of O‐silyl N,O‐ketene acetals, generated in situ from N‐alkoxy amides, a phenyl group can be introduced onto the α‐carbon atom of amides through N−O bond cleavage in a two‐step, one‐pot process. The asymmetric synthesis of α‐aryl amides through the diastereoselective arylation of a chiral N,O‐ketene acetal is also described.

Remarkable Reactivity Differences between Glucosides with Identical Leaving Groups.

Two isomeric aryl 2-deoxy-2-fluoro-β-glucosides react with a β-glucosidase at rates differing by 106-fold, despite the fact that they release the same aromatic aglycone. In contrast, the equivalent glucoside substrates react with essentially identical rate constants. Insight into the source of these surprising rate differences was obtained through a comprehensive study of the nonenzymatic (spontaneous) hydrolysis of these same substrates, wherein an approximate 105-fold difference in rates was measured, clarifying that the differences were inherent rather than being due to specific interactions with the enzyme. The possibility that an alternate nucleophilic aryl substitution mechanism was responsible for the rapid reaction of the faster substrate was excluded through 18O-labeling studies. Further exploration of the origins of these rate differences involved analysis of X-ray crystal structures as well as quantum chemical calculations, which surprisingly revealed that ground state destabilization and transition state stabilizing effects contribute almost equally to the observed reactivity differences. These studies highlight the dangers of using simple reference equilibria such as pKa values as measures of leaving group ability.

Regio-specific synthesis of new 1-(tert-butyl)-1H-pyrazolecarboxamide derivatives

Regio-specific and non-regiospecific condensation reactions on 1,3-dicarbonyl compounds rendered 1,3,5-trisubstituted pyrazoles. Herein, the control of regio-specificity was a significant improvement in pyrazole research. A high yield acylation of poorly nucleophilic aryl amines, which resulted in mono- or diacylated products depending on the reaction conditions, is described. As a result, a library of potentially bioactive compounds was obtained.

Palladium‐Catalyzed Direct β‐C−H Arylation of Ketones with Arylboronic Acids in Water

AbstractA palladium‐catalyzed direct β‐C−H arylation of ketones was developed under mild conditions in water, featuring commercially available arylboronic acids as nucleophilic aryl sources and o‐iodoxybenzoic acid as the oxidant. The method provides a concise route to access β‐arylated ketones. Preliminary studies indicated that direct asymmetric β‐C−H arylation of ketones could be achieved by this strategy.magnified image

Synthesis of Benzodioxane and Benzofuran Scaffolds Found in Neolignans via TMS Triflate Mediated Addition to 1,4-Benzo­dioxane Hemiacetals

This research reports the successful asymmetric synthesis of both a 9-hydroxy-5′-methoxy-1,4-benzodioxane framework and a highly functionalised benzofuran scaffold. Both synthetically desirable structures are the result of a Lewis acid catalysed addition of an aryl nucleophile to 1,4-benzodioxane hemiacetals and offer a route towards the synthesis of a number of naturally occurring neolignans.

Oxidative coupling of Michael acceptors with aryl nucleophiles produced through rhodium-catalyzed C-C bond activation.

Utilizing rhodium catalysis, aryl nucleophiles generated via carbon-carbon single bond activation successfully undergo oxidative coupling with Michael acceptors. The reaction scope encompasses a broad range of nucleophiles generated from quinolinyl ketones as well as a series of electron deficient terminal alkenes, illustrating the broad potential of intersecting carbon-carbon bond activation with synthetically useful coupling methodologies. The demonstrated oxidative coupling produces a range of cinnamyl derivatives, several of which are challenging to prepare via conventional routes.

Asymmetric cross-coupling of alkyl, alkenyl and (hetero)aryl nucleophiles with racemic allyl halides.

Single enantiomer molecules are important for the pharmaceutical and agrochemical industries and increasingly so in materials science. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. Dynamic asymmetric processes are powerful methods that use racemic mixtures of chiral substrates as starting material. This Feature Article focuses on asymmetric additions to racemic substrates using non-stabilized sp2- and sp3-hybridized nucleophiles. These reactions bear considerable resemblance to traditional sp2-sp2 cross-coupling reactions in terms of the starting materials used and the products obtained, but the reaction mechanisms are necessarily different.

2,2,2-Trifluoroethanol as a solvent to control nucleophilic peptide arylation.

The SNAr arylation of peptides with perfluoroaromatics provides a route by which to install a useful chemical handle that enables both 19F-NMR analysis and further chemical modification. However, chemo-selective arylation in peptides containing multiple nucleophilic side chains currently presents a challenge to the field. Herein, we demonstrate that employing 2,2,2-trifluoroethanol (TFE) as a solvent in peptide SNAr reactions significantly improves nucleophile-selectivity when compared to N,N'-dimethylformamide (DMF).

Atom- and step-economical nucleophilic arylation of azaaromatics via electrochemical oxidative cross C–C coupling reactions

A simple and efficient electrochemical method for the synthesis of asymmetrical bi(het)aryls through direct functionalization of the C(sp2)–H bond in azaaromatics with fragments of (hetero)aromatic nucleophiles has been developed.

ChemInform Abstract: Conjugate Addition of Aryl Nucleophiles to α,β‐Unsaturated Cinnamic Acid Derivatives Containing Evans Type Chiral Auxiliaries.

ChemInform Abstract: Conjugate Addition of Aryl Nucleophiles to α,β‐Unsaturated Cinnamic Acid Derivatives Containing Evans Type Chiral Auxiliaries.

ChemInform Abstract: Recent Developments for the Photoinduced Ar—X Bond Dissociation Reaction

AbstractReview: 56 refs.

Synthesis and Intramolecular Azo Coupling of 4-Diazopyrrole-2-carboxylates: Selective Approach to Benzo and Hetero [c]-Fused 6H-Pyrrolo[3,4-c]pyridazine-5-carboxylates.

A high yield synthesis of fluorescent benzo, thieno, and furo [c]-fused methyl 7-aryl-6H-pyrrolo[3,4-c]pyridazine-5-carboxylates, including unprecedented heterocyclic skeletons, was performed by the transformation of methyl 4-aminopyrrole-2-carboxylate into the corresponding diazo compound, followed by intramolecular azo coupling under acid conditions onto a nucleophilic aryl or hetaryl group in the 3-position. Azo coupling is completely regioselective and, according to DFT calculations, a kinetically controlled reaction. N-Methylation of 1,3-disubstituted 2H-pyrrolo[3,4-c]cinnolines occurs selectively at N5 under kinetic control, leading exclusively to 5-methyl-5H-pyrrolo[3,4-c]cinnoline derivatives.

Conjugate addition of aryl nucleophiles to α,β-unsaturated cinnamic acid derivatives containing Evans type chiral auxiliaries

Cinnamides containing oxazolidin-2-one type auxiliaries have been prepared. A novel pathway to chiral 4-aryl-6-methyl-3,4-dihydrocoumrines via the asymmetric conjugate addition of arylmagnesium bromides to these cinnamides is described.