199277-70-8

Upstream product

• 16369-05-4 valinol 
• 1343099-21-7 C₉H₁₂N₂O 
• 1620-75-3 2-Cyano-6-methylpyridine 
• 931-19-1 2-methylpyridine N-oxide 
• 109-06-8 α-picoline 
• 129821-92-7 methyl 6-methylpicolinimidate 
• 2026-48-4 (S)-valinol 

Downstream Products

• 2417528-13-1 (S)-2-(6-benzhydrylpyridin-2-yl)-4-isopropyl-4,5-dihydrooxazole 

Relevant academic research and scientific papers

Site-Selective Ni-Catalyzed Reductive Coupling of α-Haloboranes with Unactivated Olefins

A mild, chemo- and site-selective catalytic protocol that allows for incorporating an alkylboron fragment into unactivated olefins is described. The use of internal olefins enables C-C bond-formation at remote sp3 C-H sites, constituting a complementary and conceptually different approach to existing borylation techniques that are currently available at sp3 centers.

Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enecarbamates

Chiral alkyl amines are omnipresent as bioactive molecules and synthetic intermediates. The catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enecarbamates (N-Cbz-protected enamines) and alkyl halides with high regio- and enantioselectivity. The method works for both nonactivated and activated alkyl halides and is able to produce enantiomerically enriched amines with two minimally differentiated α-alkyl substituents. The mild conditions lead to high functional group tolerance, which is demonstrated in the postproduct functionalization of many natural products and drug molecules, as well as the synthesis of chiral building blocks and key intermediates to bioactive compounds.

Ligand-Controlled Regiodivergence in Nickel-Catalyzed Hydroarylation and Hydroalkenylation of Alkenyl Carboxylic Acids**

A nickel-catalyzed regiodivergent hydroarylation and hydroalkenylation of unactivated alkenyl carboxylic acids is reported, whereby the ligand environment around the metal center dictates the regiochemical outcome. Markovnikov hydrofunctionalization products are obtained under mild ligand-free conditions, with up to 99 % yield and >20:1 selectivity. Alternatively, anti-Markovnikov products can be accessed with a novel 4,4-disubstituted Pyrox ligand in excellent yield and >20:1 selectivity. Both electronic and steric effects on the ligand contribute to the high yield and selectivity. Mechanistic studies suggest a change in the turnover-limiting and selectivity-determining step induced by the optimal ligand. DFT calculations reveal that in the anti-Markovnikov pathway, repulsion between the ligand and the alkyl group is minimized (by virtue of it being 1° versus 2°) in the rate- and regioselectivity-determining transmetalation transition state.

Enantioselective Ni-Catalyzed Electrochemical Synthesis of Biaryl Atropisomers

A scalable enantioselective nickel-catalyzed electrochemical reductive homocoupling of aryl bromides has been developed, affording enantioenriched axially chiral biaryls in good yield under mild conditions using electricity as a reductant in an undivided cell. Common metal reductants such as Mn or Zn powder resulted in significantly lower yields in the absence of electric current under otherwise identical conditions, underscoring the enhanced reactivity provided by the combination of transition metal catalysis and electrochemistry.

Chemoselective oxidation of polyols with chiral palladium catalysts

Chiral palladium-based catalysts derived from pyridinyl oxazoline (pyOx) ligands catalyze the oxidation of alcohols, including 1,2-diols, triols, and tetraols, with high regio- and chemoselectivity. Screening of various chiral oxazoline-derived ligands for the oxidation of a model diol, 1,2-propanediol (1,2-PD), revealed that the nature of the ligand had a significant influence on the activity and chemoselectivity for oxidation of vicinal diols. The PyOx ligands containing an α-methyl substituent were the most active for the oxidation of 1,2-PD using benzoquinone as the terminal oxidant. Oxidation of vicinal diols and polyols occurs selectively at the secondary alcohol to afford α-hydroxy ketones in isolated yields of 62-87%. Chemoselective oxidation of meso-erythritol with the chiral [(S)-(α-Me(tert-Bu)PyOx)Pd(OAc)] 2[OTf]2 afforded (S)-erthyrulose in 62% yield and 24% ee.

Chiral oxazolinylpyridines as ligands for enantioselective palladium catalysed allylic substitution

Chiral oxazolinylpyridines were prepared and assessed in the enantioselective palladium catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate. Enantioselectivity up to 91% was obtained.