Reductive coupling of polyfunctionalized organobismuth and organolead arylating reagents in the synthesis of benzopyran derivatives

Benzopyran derivatives were synthesized in good yields by the reactions of tris[2-(chloromethyl)phenyl]bismuth diacetate and 2-(halomethyl)aryllead triacetates with phenols and naturally occurring 4-hydroxycoumarins in the presence of bases according to a three-step one-pot procedure. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2520–2529, November, 2005.     

N-Arylation of azoles with low basicity by 1,4-dimethoxybenzene during undivided electrolysis

The reactions of 1,4-dimethoxybenzene with 4-nitropyrazole, 3,4-dinitro-5-methylpyrazole, 1,2,4-triazole, 3-nitro-1,2,4-triazole, and tetrazole were studied during undivided amperostatic electrolysis on a Pt electrode in MeCN, CH₂Cl₂, and MeOH. The main reaction products were 2-azolyl-1,4-dimethoxybenzenes and (or) 1,4-diazolyl-1,4-dimethoxycyclohexa-2,5-dienes. In all cases except 1,2,4-triazole, N-arylation occurs only in the presence of the Alk₄N⁺ salts of azoles or 2,4,6-trimethylpyridine as a base. The mechanism of the reactions is discussed.     

Synthesis of novel 9-aryl and heteroarylpurine derivatives via copper mediated coupling reaction

A series of 9-(hetero)arylpurine derivatives has been prepared through N-arylation of 6-chloropurine with boronic acids in the presence of copper(II) acetate. Screening reaction conditions in terms of bases and solvents led to the successful coupling of a series of sterically demanding (hetero)arylboronic acids, never described so far. The coupling products were next readily converted into the target adenine derivatives. The described procedure provides easy access to original fragments for screening applications. Moreover these 9-aryl-6-chloropurine derivatives might be useful as intermediates for the preparation of purine derivatives with potential biological properties.     

α-Arylation and Ring Expansion of Annulated Cyclobutanones: Stereoselective Synthesis of Functionalized Tetralones

α-Arylcyclobutanones display unique reactivity that makes them valuable synthetic intermediates and target molecules. We describe the preparation of α-aryl- and α-heteroarylcyclobutanones through a direct α-arylation reaction. Problematic fragmentations are avoided by the use of LiO^tBu, which promotes a rapid but reversible self-aldol reaction that slowly releases the enolate required for α-arylation. We also demonstrate the ring expansion of α-arylcyclobutanones, a process that is highlighted in the stereoselective synthesis of 1-methoxy coniothyrinone D.     

Preparation and Application of Solid,Salt‐Stabilized Zinc Amide Enolates with Enhanced Air and Moisture Stability

The treatment of various N‐morpholino amides with TMPZnCl⋅LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) and Mg(OPiv)₂ in THF at 25 °C provides solid zinc enolates with enhanced air and moisture stability (t _1/2 in air: 1–3 h) after solvent evaporation. These enolates undergo Pd‐ and Cu‐catalyzed cross‐couplings with (hetero)aryl bromides as well as allylic and benzylic halides. The arylated N‐morpholino amides were converted into various ketones by LaCl₃⋅2 LiCl mediated acylation with Grignard reagents. The new, solid enolates were used to prepare a potent anti‐breast‐cancer drug candidate in six steps and 23 % overall yield.     

Vinyl Cation Stabilization by Silicon Enables a Formal Metal‐Free α‐Arylation of Alkyl Ketones

The ability of silicon to stabilize vinyl cationic species leads to a redox arylation of alkynes whereby the stringent limitations of reactivity and regioselectivity of alkyl‐substituted alkynes are lifted. This allows the synthesis of a range of α‐silyl‐α′‐arylketones under mild conditions in good to excellent yields and with high functional group tolerance, whereby the silicon moiety in the final products can either be removed for a formal acetone monoarylation transform, or capitalized upon for subsequent electrophilic substitutions at either side of the carbonyl group.     

Chiral Primary Amine Catalyzed α-Arylation of Simple Ketones via Asymmetric Retro-Claisen Cleavage

Highly enantioselective α-arylation of simple ketones has been achieved by chiral primary amine catalyzed asymmetric retro-Claisen cleavage of β-diketones. This mild organocatalytic strategy enables the construction of α-aryl tertiary carbon stereocenters in good yields and excellent enantioselectivities (up to 98 % ee) with the para-quinone monoimines as aryl sources. Furthermore, oxidative catalytic asymmetric α-arylation has also been realized with free p-aminophenols.     

Synthetic and mechanistic aspects of α-alkylation and α-arylation of β-dicarbonyl compoundsvia their transition metal complexes

Some transition metal complexes of β-dicarbonyl compounds react with electrophiles at α-C. These reactions, carried out under neutral conditions, offer a broader scope than their conventional counterparts, and are generally performed in the presence of stoichiometric or catalytic amounts of strong bases. Mechanistic observations using different reaction conditions are also relevant from a synthetic point of view. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 418–427, March, 1997.     

Exploring organic reactions using simple cyclodiphosphazanes

Phosphine-activated reactions of alkynes/alkenes/allenes as well as the Mitsunobu reaction involve a rich phosphorus chemistry. With the aid of simple cyclodiphosphazanes, characterization of many compounds analogous to the proposed intermediates in such reactions has been accomplished. Use of a cyclodiphosphazane in Pd-catalyzed N-arylation reactions is highlighted. Results on molecular non-stoichiometry in phosphorus compounds and on the use of chiral phosphorus systems are discussed. Synthesis of allenylphosphoramides involving a cyclodiphosphazane is also described. X-ray structures of the new compounds [(t-BuNH)(PhCH₂CH(CN)CH₂-)P(μ-N-t-Bu)₂P(NH-t-Bu)]⁺[HCO₃]⁻ (13), [(t-BuNH)P(μ-N-t-Bu)₂P(N-t-Bu)-C(CH₂)CH(C₆H₄-4-Me)-P(O)(OCH₂CMe₂CH₂O)] (18), [(i-PrNH)P(μ-N-t-Bu)₂P(N-i-Pr)-N(CO₂-i-Pr)-NH(CO₂-i-Pr)] (24), [(S)-(2-OH-1-C₁₀H₆-1′-C₁₀H₆-2′-O-P(O)(NH-t-Bu)₂] (36) and [(t-BuNH)(O)P(μ-N-t-Bu)₂P(O)(CHCCMe₂)] (40) are also reported.     

Palladium-catalyzed intramolecular γ-lactam formation of an aryl halide and an enolate: synthesis of isoindolobenzazepine alkaloids, lennoxamine, 13-deoxychilenine, and chilenine

A facile synthetic path to isoindolobenzazepine alkaloids, lennoxamine, 13-deoxychilenine, and chilenine, was established by employing a palladium-catalyzed intramolecular α-arylation of the ketone, as the key step.