Yusuke Sasano

Highly Efficient, Organocatalytic Aerobic Alcohol Oxidation

5-Fluoro-2-azaadamantane N-oxyl (5-F-AZADO) realizes a simple, organocatalytic aerobic alcohol oxidation system that has a wide scope under mild conditions at ambient pressure and temperature and is weakly acidic and halogen- and transition-metal-free. The oxoammonium nitrate (5-F-AZADO(+)NO(3)(-)) works as a bifunctional catalyst of 5-F-AZADO and NO(x) that enables the catalytic aerobic oxidation of alcohols by itself (a metal-salt-free system).

An Expeditious Entry to 9-Azabicyclo[3.3.1]nonane N-Oxyl (ABNO): Another Highly Active Organocatalyst for Oxidation of Alcohols

A practical, three-step synthetic route to 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO, 3), an unhindered, stable class of nitroxyl radical, has been developed. ABNO exhibits a highly active nature compared with TEMPO in the catalytic oxidation of alcohols to their corresponding carbonyl compounds.

Highly chemoselective aerobic oxidation of amino alcohols into amino carbonyl compounds.

The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has constrained chemists to adopting an indirect route, such as a protection/deprotection strategy, to attain their goal. Described herein is a highly chemoselective aerobic oxidation of unprotected amino alcohols to their amino carbonyl compounds in which 2-azaadamantane N-oxyl (AZADO)/copper catalysis is used. The catalytic system developed leads to the alcohol-selective oxidation of various unprotected amino alcohols, carrying a primary, secondary, or tertiary amino group, in good to high yield at ambient temperature with exposure to air, thus offering flexibility in the synthesis of nitrogen-containing compounds.

Highly enantioselective organocatalytic oxidative kinetic resolution of secondary alcohols using chiral alkoxyamines as precatalysts: catalyst structure, active species, and substrate scope.

The development and characterization of enantioselective organocatalytic oxidative kinetic resolution (OKR) of racemic secondary alcohols using chiral alkoxyamines as precatalysts are described. A number of chiral alkoxyamines have been synthesized, and their structure-enantioselectivity correlation study in OKR has led us to identify a promising precatalyst, namely, 7-benzyl-3-n-butyl-4-oxa-5-azahomoadamantane, which affords various chiral aliphatic secondary alcohols (ee up to >99%, k(rel) up to 296). In a mechanistic study, chlorine-containing oxoammonium species were identified as the active species generated in situ from the alkoxyamine precatalyst, and it was revealed that the chlorine atom is crucial for high reactivity and enantioselectivity. The present OKR is the first successful example applicable to various unactivated aliphatic secondary alcohols, including heterocyclic alcohols with high enantioselectivity, the synthetic application of which is demonstrated by the synthesis of a bioactive compound.

3‐Methyl‐4‐oxa‐5‐azahomoadamantane: Alkoxyamine‐Type Organocatalyst for Alcohol Oxidation

The unique behavior and eminent reactivity of organic/ inorganic nitrogen oxides have continuously attracted the attention of chemists not only because of their profound chemistry, but also because of their use in various fields of material and life sciences. Herein, we report the discovery of a novel alkoxyamine-type organocatalyst, 3-methyl-4-oxa-5azahomoadamantane (1), which enables highly efficient oxidation of primary and secondary alcohols into their corresponding carbonyl compounds using NaOCl as the terminal oxidant. The present work first shows a useful pathway from an alkoxyamine/alkoxyaminyl radical to a nitroxyl radical/oxoammonium ion under oxidative conditions (Figure 1). 3]

Synthesis of 1,3-Cycloalkadienes from Cycloalkenes: Unprecedented Reactivity of Oxoammonium Salts.

Few methods allow for the direct conversion of cycloalkenes into cycloalkadienes with high chemo- and regioselectivity. Herein, we report a convenient one-pot process for this transformation that involves the unprecedented N-preferential group transfer of N-oxoammonium salts to cycloalkenes, followed by Cope elimination, to afford cycloalkadienes at room temperature and pressure.

Highly Efficient Aerobic Oxidation of Alcohols by Using Less‐Hindered Nitroxyl‐Radical/Copper Catalysis: Optimum Catalyst Combinations and Their Substrate Scope

The oxidation of alcohols into their corresponding carbonyl compounds is one of the most fundamental transformations in organic chemistry. In our recent report, 2-azaadamantane N-oxyl (AZADO)/copper catalysis promoted the highly chemoselective aerobic oxidation of unprotected amino alcohols into amino carbonyl compounds. Herein, we investigated the extension of the promising AZADO/copper-catalyzed aerobic oxidation of alcohols to other types of alcohol. During close optimization of the reaction conditions by using various alcohols, we found that the optimum combination of nitroxyl radical, copper salt, and solution concentration was dependent on the type of substrate. Various alcohols, including highly hindered and heteroatom-rich ones, were efficiently oxidized into their corresponding carbonyl compounds under mild conditions with lower amounts of the catalysts.

Catalytic Oxygenative Allylic Transposition of Alkenes into Enones with an Azaadamantane-Type Oxoammonium Salt Catalyst

The first catalytic oxygenative allylic transposition of unactivated alkenes into enones has been developed using an oxoammonium salt as the catalyst. This reaction converts various tri- and trans-disubstituted alkenes into their corresponding enones with transposition of their double bonds at ambient temperature in good yields. The use of a less-hindered azaadamantane-type oxoammonium salt as the catalyst and a combination of two distinct stoichiometric oxidants, namely, iodobenzene diacetate and magnesium monoperoxyphthalate hexahydrate (MMPP⋅6 H2 O) are essential to facilitate the enone formation efficiently.

Nazarov Cyclization Entry to Chiral Bicyclo[5.3.0]decanoid Building Blocks and Its Application to Formal Synthesis of (−)-Englerin A

A divergent entry to the chiral bicyclo[5.3.0]decane skeletons relevant to sesqui- and higher terpenoids has been achieved. Its usefulness was demonstrated by formal synthesis of a guaiane sesquiterpenoid (-)-englerin A. The key reactions are (i) diastereoselective Nazarov cyclization for stereoselective construction of the bicyclo[5.3.0]decane skeleton, (ii) intramolecular C-H amination for tuning an oxidation state, and (iii) introduction of an alkyl group to a β-alkoxy ketone with a zinc(II) ate complex.

2-Azaadamantane N-oxyl (AZADO)/Cu Catalysis Enables Chemoselective Aerobic Oxidation of Alcohols Containing Electron-Rich Divalent Sulfur Functionalities

The chemoselective oxidation of alcohols containing electron-rich sulfur functionalities (e.g., 1,3-dithianes and sulfides) into their corresponding carbonyl compounds with the sulfur groups can sometimes be a demanding task in modern organic chemistry. A reliable method for this transformation, which features azaadamantane-type nitroxyl radical/copper catalysis using ambient air as the terminal oxidant is reported. The superiority of the developed method was demonstrated by comparing it with various conventional alcohol oxidation methods.