Chuan-Zhi Yao

Pharmaceutical-Oriented Selective Synthesis of Mononitriles and Dinitriles Directly from Methyl(hetero)arenes: Access to Chiral Nitriles and Citalopram

A pharmaceutical-oriented, transition-metal-free, cyanide-free one-step direct transformation of methylarenes to aryl nitriles is described. For the dimethylarenes, the selectivity can be well-controlled to form mononitriles or dinitriles. Enantioenriched nitriles can also be synthesized by this method. As a pharmaceutically practical method, the antidepressant drug citalopram was synthesized from cheap and commercially abundant m-xylene on a gram scale in high yield, avoiding transition-metal residues and toxic cyanides.

Transition-Metal-Free Deacylative Cleavage of Unstrained C(sp3)–C(sp2) Bonds: Cyanide-Free Access to Aryl and Aliphatic Nitriles from Ketones and Aldehydes

A transition-metal-free deacylative C(sp(3))-C(sp(2)) bond cleavage for the synthetically practical oxidative amination of ketones and aldehydes to nitriles is first described, using cheap and commercially abundant NaNO2 as the oxidant and the nitrogen source. Various nitriles bearing aryl, heteroaryl, alkyl, and alkenyl groups could be smoothly obtained from ketones and aldehydes in high yields, avoiding highly toxic cyanides or transition metals.

Ruthenium-catalyzed asymmetric N-demethylative rearrangement of isoxazolidines and its application in the asymmetric total syntheses of (-)-(1R,3S)-HPA-12 and (+)-(1S,3R)-HPA-12.

An asymmetric N-demethylative rearrangement of 1,2-isoxazolidines catalyzed by ruthenium is described. Enantioenriched syn-1,3-aminoalcohols as well as cis-1,3-oxazinanes, which are useful building blocks, can be efficiently prepared stereospecifically by this reaction in good yields, via the isoxazolidine intermediates in situ generated from a nitrone bearing a chiral auxiliary and styrenes. This asymmetric reaction was also applied in the asymmetric total syntheses of both (-)-(1R,3S)-HPA-12 and (+)-(1S,3R)-HPA-12.

Synthesis of syn-1,3-Aminoalcohols via a Ru-Catalyzed N-Demethylative Rearrangement of Isoxazolidines and Its Application in a Three-Step Total Synthesis of HPA-12

A highly efficient ruthenium-catalyzed stereospecific N-demethylative rearrangement of isoxazolidines to synthetically useful N-H-1,3-oxazinanes is described. 1,3-Oxazinanes are useful building blocks, which can be further converted to N-H-1,3-aminoalcohols in one step. This new method was used in a three-step gram-scale total synthesis of HPA-12 in an overall 24% yield.

Ru-catalyzed rearrangement of N-methyl isoxazolidines to N-H 1,3-oxazinanes: a strategy of self-hydride transferring cleavage of N-O bonds.

A strategy of ruthenium-catalyzed self-hydride transferring cleavage of N-O bonds was designed and utilized in a cascade 1,3-dipolar cyclization of alkenes and N-methyl nitrones followed by an N-demethylative rearrangement, furnishing synthetically useful N-H 1,3-oxazinanes.

tert-Butyl Nitrite: Organic Redox Cocatalyst for Aerobic Aldehyde-Selective Wacker–Tsuji Oxidation

An aldehyde-selective aerobic Wacker-Tsuji oxidation is developed. Using tert-butyl nitrite as a simple organic redox cocatalyst instead of copper or silver salts, a variety of aldehydes were achieved as major products in up to 30/1 regioselectivity as well as good to high yields at room temperature.

Transition-Metal-Free Self-Hydrogen-Transferring Allylic Isomerization

Phenanthroline and tert-butoxide have been established as powerful radical initiators in reactions such as the SRN1-type coupling reactions due to the cooperation of large heteroarenes and a special feature of tert-butoxide. The first phenanthroline-tert-butoxide-catalyzed transition-metal-free allylic isomerization is described. The resulting ketones are key intermediates for indenes. The control experiments rule out the base-promoted allylic anion pathway. The radical pathway is supported by experimental evidence that includes kinetic study, kinetic isotope effect, isotope-labeling experiments, trapping experiments, and EPR experiments.

n Bu4NOTf-promoted radical self-hydrogen transferring isomerization under transition metal-free conditions

We report the first allylic isomerization of alcohols catalyzed by nBu4NOTf generated in situ from tetrabutylammonium triflate and potassium tert-butoxide. Substituted ketones could be prepared under mild conditions in good to excellent yields. The relationship between catalysts and their reactivity has been investigated by systematic kinetic studies. The radical nature of this isomerization reaction has also been confirmed.