Kazunori Nagao

Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research, providing vital information about the biological fate of drugs and drug metabolites. Herein we demonstrate that a photoredox-mediated hydrogen atom transfer protocol can efficiently and selectively install deuterium (D) and tritium (T) at α-amino sp³ carbon-hydrogen bonds in a single step, using isotopically labeled water (D₂O or T₂O) as the source of

We found that N-heterocyclic carbene catalysis promoted the unprecedented decarboxylative coupling of aryl aldehydes and tertiary or secondary alkyl carboxylic acid-derived redox-active esters to produce aryl alkyl ketones. The mild and transition-metal-free reaction conditions are attractive features of this method. The power of this protocol was demonstrated by the functionalization of pharmaceutical drugs and natural product. A reaction pathway involving single electron transfer from an enola

The <i>N</i>-heterocyclic carbene-catalyzed radical relay enables the vicinal alkylacylation of styrenes, acrylates and acrylonitrile using aldehydes and tertiary alkyl carboxylic acid-derived redox-active esters. This protocol introduces tertiary alkyl groups and acyl groups to C-C double bonds with complete regioselectivity to produce functionalized ketone derivatives. The radical relay mechanism involves single electron transfer from the enolate form of a Breslow intermediate and radical addi

This manuscript reports a visible-light-mediated organosulfide catalysis that enables the decarboxylative coupling between simple aliphatic alcohol and tertiary or secondary alkyl carboxylic acid-derived redox active esters to produce a C(sp³)-O-C(sp³) fragment. Results of the coupling using other heteroatom nucleophiles such as water, amides, and thiols are also described.

We demonstrate Markovnikov hydroalkoxylation of unactivated alkenes using alcohols through a triple catalysis consisting of photoredox, cobalt, and Brønsted acid catalysts under visible light irradiation. The triple catalysis realizes three key elementary steps in a single catalytic cycle: (1) Co(III) hydride generation by photochemical reduction of Co(II) followed by protonation, (2) metal hydride hydrogen atom transfer (MHAT) of alkenes by Co(III) hydride, and (3) oxidation of the alkyl Co(III

Trialkylphosphine organocatalysts have enabled anti-selective vicinal silaboration and diboration of the C-C triple bond in alkynoates to produce β-boryl-α-silyl acrylates and α,β-diboryl acrylates, respectively. The anti stereoselectivity was complete and robust. A variety of functional groups were tolerated in the alkynoates. The two vicinally installed heteroatom substituents of the β-boryl-α-silyl acrylates and α,β-diboryl acrylates could be differentiated and transformed in a stepwise manne

A designed thiazolium-type N-heterocyclic carbene (NHC) catalyst having an N-neopentyl group and seven-membered backbone structure was achieved through the use of aliphatic aldehydes as acyl donors in the decarboxylative radical coupling with aliphatic carboxylic acid derived-redox active esters. The NHC catalyst also enabled the vicinal alkylacylation of vinyl arenes using aliphatic aldehydes and redox-active esters through a radical relay mechanism. These reactions provided the synthetic route

We found that trialkylphosphine organocatalysts promoted unprecedented anti-carboboration of alkynoates with alkyl-, alkenyl-, or arylboranes to form β-boryl acrylates. The regioselectivity of the carboboration across the polar C-C triple bond exhibited inverse electronic demand, with the less electronegative B atom being delivered to the positively charged β carbon atom. The regioselectivity and the anti stereoselectivity were both complete and robust. In addition, the substrate scope was broad

An NHC-catalyzed radical relay enabled the vicinal alkylacylation of alkenes using aldehydes and tertiary α-bromo esters as a versatile route to δ-keto esters bearing an all-carbon quaternary center at the position α to the ester. The protocol was applicable to the reaction of tertiary α-bromoamides to afford δ-keto amides. This protocol enabled the conversion of readily available starting materials to congested and functionalized δ-ketocarbonyls in a single step without using transition metals.

Trialkylphosphine organocatalysts have enabled regioselective anti-hydroboration of internal alkynes with pinacolborane reagents to provide ( E)-disubstituted alkenylboronate compounds. The alkenylboronate can be used for derivatizations, such as protodeborylation, Suzuki-Miyaura coupling, conjugate reduction, and Diels-Alder reactions.

The stereochemical courses of the copper-catalyzed allyl-alkyl coupling between enantioenriched chiral allylic phosphates and alkylboranes were switchable between 1,3-anti and 1,3-syn selectivities by the choice of solvents and achiral alkoxide bases with different steric demands. The reactions with γ-silylated allylic phosphates allow efficient synthesis of enantioenriched chiral allylsilanes with tertiary or quaternary carbon stereogenic centers. Cyclic and acyclic bimodal participation of alk

This manuscript describes a visible-light-mediated organophotoredox catalytic process for vicinal difunctionalization of alkenes using heteroatom nucleophiles and aliphatic redox active esters. A wide range of heteroatom nucleophiles including alcohols, water, carboxylic acids, amides, and halogens can be used for this reaction. This radical relay type reaction allows forging of C(sp³)-C(sp³) with a carbon-centered radical and C(sp³)-heteroatom bonds with a benzy

N-Heterocyclic carbene catalysis enabling vicinal trichloromethylacylation of alkenes using tetrachloromethane and aldehydes has been developed. The reaction involves single electron transfer from the enolate form of the Breslow intermediate to tetrachloromethane to generate the persistent Breslow intermediate-derived ketyl radical and a transient trichloromethyl radical. After radical addition of the trichloromethyl radical to an alkene, the prolonged alkyl radical is preferentially captured by

An organophotoredox-catalyzed decarboxylative cross-coupling between azole nucleophiles and aliphatic carboxylic acid-derived redox-active esters is demonstrated. This protocol efficiently installs various tertiary or secondary alkyl fragments onto the nitrogen atom of azole nucleophiles under mild and transition-metal-free conditions. The pyridinium additive successfully inhibits the formation of elimination byproducts from the carbocation intermediate. This reaction is applicable to the synthe