Non-Directed C-H Arylation of Anisole Derivatives via Pd/S,O-Ligand Catalysis.

Non-directed C-H arylation is one of the most efficient methods to synthesize biaryl compounds without the need of the prefuctionalization of starting materials, or the installment and removal of directing groups on the substrate. A direct C-H arylation of simple arenes as limiting reactants remains a challenge. Here we disclose a non-directed C-H arylation of anisole derivatives as limiting reagents with aryl iodides under mild reaction conditions. The arylated products are obtained in synthetically useful yields and the arylation of bioactive molecules is also demonstrated. Key to the success of this methodology is the use of a one-step synthesized S,O-ligand.

meta-C-H Arylation of Aniline Derivatives via Palladium/ S,O-Ligand/Norbornene Cooperative Catalysis.

Aromatic amines are ubiquitous moieties in organic molecules and their direct functionalization is of great interest in many research areas due to their prevalence in pharmaceuticals and organic electronics. While several synthetic tools exist for the ortho- and para-functionalization of anilines, the functionalization of the less reactive meta-position is not easy to achieve with current methods. To date, the meta-C-H arylation of aniline derivatives has been restricted to either the use of directing groups & templates, or their transformation into anilides & quaternary anilinium salts. Herein, we report the first general and efficient meta-C-H-arylation of non-directed aniline derivatives via cooperative catalysis with a palladium-S,O-ligand-norbornene system. The reaction proceeds under mild conditions with a wide range of aniline derivatives and aryl iodides, while being operationally simple and scalable. Our preliminary mechanistic investigation-including the isolation of several palladium complexes and deuterium experiments-reveal useful insights into the substituent-effects of both the aniline-substrate and the norbornene-mediator during the meta-C-H activation step.

S,O-Ligand Promoted meta-C-H Arylation of Anisole Derivatives via Palladium/Norbornene Catalysis.

Reversing the conventional site-selectivity of C-H activation processes provides new retrosynthetic disconnections to otherwise unreactive bonds. Here, we report a new catalytic system based on palladium/norbornene and an S,O-ligand for the meta-C-H arylation of aryl ethers that significantly outperforms previously reported systems. We demonstrate the unique ability of this system to employ alkoxyarene substrates bearing electron donating and withdrawing substituents. Additionally, ortho-substituted aryl ethers are well tolerated, overcoming the "ortho constraint", which is the necessity to have a meta-substituent on the alkoxyarene to achieve high reaction efficiency, by enlisting novel norbornene mediators. Remarkably, for the first time the monoarylation of alkoxyarenes is achieved efficiently enabling the subsequent introduction of a second, different aryl coupling partner to rapidly furnish unsymmetrical terphenyls. Further insight into the reaction mechanism was achieved by isolation and characterization of some Pd-complexes-before and after meta C-H activation-prior to evaluation of their respective catalytic activities.

Diastereoselective Synthesis of ß-Lactams by Ligand-Controlled Stereodivergent Intramolecular Tsuji-Trost Allylation.

The diastereoselective synthesis of highly substituted ß-lactams by intramolecular Tsuji-Trost allylation is reported. Judicious selection of the ligand on palladium allows selective access to either the trans isomer (in generally good to excellent yield with very high diastereomeric excess) or cis isomer (with yields and diastereoselectivity ranging from modest to excellent depending on the substrate). The reaction proceeds under exceedingly mild conditions (rt, no additives) with a broad range of substrates, which are readily accessible by the Ugi reaction.