Bimetallic Ru/Ru-Catalyzed Asymmetric One-Pot Sequential Hydrogenations for the Stereodivergent Synthesis of Chiral Lactones.

Asymmetric sequential hydrogenations of α-methylene γ- or δ-keto carboxylic acids are established in one-pot using a bimetallic Ru/Ru catalyst system, achieving the stereodivergent synthesis of all four stereoisomers of both chiral γ- and δ-lactones with two non-vicinal carbon stereocenters in high yields (up to 99%) and with excellent stereoselectivities (up to >99% ee and >20:1 dr). The compatibility of the two chiral Ru catalyst systems is investigated in detail, and it is found that the basicity of the reaction system plays a key role in the sequential hydrogenation processes. The protocol can be performed on a gram-scale with a low catalyst loading (up to 11000 S/C) and the resulting products allow for many transformations, particularly for the synthesis of several key intermediates useful for the preparation of chiral drugs and natural products.

PdII -Catalyzed Oxidative Tandem aza-Wacker/Heck Cyclization for the Construction of Fused 5,6-Bicyclic N,O-Heterocycles.

A PdII -catalyzed oxidative tandem cyclization was developed for the construction of fused 5,6-bicyclic N, O-heterocycles. This reaction was enabled by the combined use of a 3-methylpyridine ligand and pentafluorobenzoic acid additive. A range of heterocyclic products with different substituents could be prepared in moderate to good yields via this methodology. Several transformations, including a scaled-up preparation of product 2 a, were also carried out showing the good applicability of our methodology.

Asymmetric Aza-Wacker-Type Cyclization of N-Ts Hydrazine-Tethered Tetrasubstituted Olefins: Synthesis of Pyrazolines Bearing One Quaternary or Two Vicinal Stereocenters.

We have developed an asymmetric aza-Wacker-type cyclization of N-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the C═C double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a syn-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is cis to the intranucleophilic group participates more readily in ß-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, ß-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps.

Pd(II)-Catalyzed Asymmetric Addition of Arylboronic Acids to Isatin-Derived Ketimines.

A Pd(II)/Pyrox-catalyzed enantioselecitve addition of arylboronic acids to 3-ketimino oxindoles was developed, providing chiral 3-amino-2-oxindoles with a quaternary stereocenter in high yields and with good enantioselectivities. A variety of functionalized 3-ketimino oxindoles can be used, and the method tolerates some variation in arylboronic acid scope. This asymmetric arylation provides an alternative efficient catalytic method for the preparation of chiral 3-aryl-3-amino-2-oxindoles, which also represents the first example of a Pd(II)-catalyzed addition of arylborons to exocyclic ketimines.

Palladium-Catalyzed Aerobic Aminooxygenation of Alkenes for Preparation of Isoindolinones.

A palladium-catalyzed intramolecular isoindolinone-forming aminooxygenation of alkenes with 1 atm of oxygen as oxidant is reported. A variety of functionalized alkenes and carboxylic acids can be used, and high yields were observed. Preliminary mechanistic studies revealed that the aminooxygenation products were formed through the oxidation of a C-Pd(II) species using a strong oxidant, peroxide, which is generated in situ from a Pd(OAc)2/bpy/O2/HOAc catalytic system.