Palladium‐Catalyzed Enantioselective C?H Arylation for the Synthesis of P‐Stereogenic Compounds

A palladium‐catalyzed enantioselective C H arylation of N‐(o‐bromoaryl)‐diarylphosphinic amides is described for the synthesis of phosphorus compounds bearing a P‐stereogenic center. The method provides good enantioselectivities and high yields. The products were readily transformed into P‐chiral biphenyl monophosphine ligands.     

Palladium‐Catalyzed Direct C?H Arylation of Isoxazoles at the 5‐Position

A palladium‐catalyzed direct arylation of isoxazoles with aryl iodides has been achieved. The C H bond at the 5‐position is activated selectively to give coupling products in moderate to good yields. This direct arylation was applied to the synthesis of a spiro‐type chiral ligand, which proved to be most effective to the palladium‐catalyzed tandem cyclization of a dialkenyl alcohol.     

Palladium‐Catalyzed Direct C?H Arylation of Isoxazoles at the 5‐Position

A palladium‐catalyzed direct arylation of isoxazoles with aryl iodides has been achieved. The C H bond at the 5‐position is activated selectively to give coupling products in moderate to good yields. This direct arylation was applied to the synthesis of a spiro‐type chiral ligand, which proved to be most effective to the palladium‐catalyzed tandem cyclization of a dialkenyl alcohol.     

Double C?H Functionalization in Sequential Order: Direct Synthesis of Polycyclic Compounds by a Palladium‐Catalyzed C?H Alkenylation–Arylation Cascade

Palladium‐catalyzed cascade C? H alkenylation and arylation provides convenient access to polycyclic aromatic compounds. Treatment of 3‐bromoaniline derivatives bearing a bromocinnamyl group on the nitrogen atom with a catalytic amount of [Pd(OAc)₂] and PCy₃?HBF₄ in the presence of Cs₂CO₃ in dioxane affords naphthalene‐fused indole derivatives in good yields. This double cyclization reaction is also applicable to heterocyclic substrates, giving fused indoles containing a heteroaromatic ring such as dibenzofuran, dibenzothiophene, carbazole, indole, or benzofuran through heterocyclic C? H arylation. When using a 2,6‐unsubstituted aniline derivative, the first C? H arylation preferentially proceeds at the more hindered position of the aniline ring.     

C?H Bond Arylation in the Synthesis of Aryltetralin Lignans: A Short Total Synthesis of Podophyllotoxin

A short total synthesis of podophyllotoxin, the prototypical aryltetralin lignan natural product, is reported. Key to the success of this synthetic pathway is a Pd‐catalyzed C(sp³)–H arylation reaction enabled by a conformational biasing element to promote C–C reductive elimination over an alternative C N bond‐forming pathway. This strategy allows for access to the natural product in five steps from commercially available bromopiperonal, and sheds light on subtle conformational effects governing reductive elimination pathways from high‐valent palladium centers.     

Synthesis of Asymmetrically Substituted Terpyridines by Palladium‐Catalyzed Direct C?H Arylation of Pyridine N‐Oxides

The synthesis of asymmetrically substituted 2,2′:6′,2′′‐terpyridines is reported. First, palladium‐catalyzed C? H arylation of pyridine N‐oxides with substituted bromopyridines gave 2,2′‐bipyridine N‐oxides, which were further arylated in a second step to form 2,2′:6′,2′′‐terpyridine N‐oxides. Yields of up to 77 % were obtained with N‐oxides bearing an electron‐withdrawing ethoxycarbonyl substituent in the 4‐position. Pd(OAc)₂ with either P(tBu)₃ or P(o‐tolyl)₃ was used as the catalyst. Cyclometalated complexes derived from Pd(OAc)₂ and these phosphines were also effective. K₃PO₄ as the base gave better results than K₂CO₃. Subsequent deoxygenation with H₂ and Pd/C as the catalyst gave the asymmetrically substituted 2,2′:6′,2′′‐terpyridines in near quantitative yield. This reaction sequence significantly reduces the number of steps required in comparison with known cross‐coupling methods and therefore allows convenient and scalable access to substituted terpyridines.     

Oxindole Synthesis by Direct Coupling of C?H and C?H Centers

An sp ² /sp ³ get‐together : A novel and efficient method can be used to synthesize 3,3‐disubstitued oxindoles by the direct intramolecular oxidative coupling of an aryl C? H and a C? H center (see scheme; DMF=N,N‐dimethylformamide).

     

Iridium Catalysis for C?H Bond Arylation of Heteroarenes with Iodoarenes

Efficient couplings using equimolar quantities of each coupling partner and multiple C? H bond arylation reactions are achieved with an Ir‐based catalytic system for the C? H bond arylation of electron‐rich heteroarenes with iodoarenes to construct extended π‐systems. The dramatic ligand effect on reaction efficiency leads to the discovery that Crabtree's catalyst (see scheme) is the optimal catalyst precursor.