A Dual Cobalt and Photoredox Catalysis for Hydrohalogenation of Alkenes.

We demonstrate hydrohalogenation of aliphatic alkenes with collidine·HX salts through dual photoredox/cobalt catalysis. The dual catalysis enables conversion of a proton and a halide anion from collidine·HX salt to a nucleophilic hydrogen radical equivalent and an electrophilic halogen radical equivalent and delivery of them to an alkene moiety. This protocol allows for introduction of fluorine, chlorine, bromine, or iodine atom to alkene, producing highly functionalized alkyl halides.

A Quadruple Catalysis Enabling Intermolecular Branch-Selective Hydroacylation of Styrenes.

A quadruple N-heterocyclic carbene/cobalt/photoredox/Brønsted base catalysis to realize branch-selective hydroacylation of styrenes with aromatic and aliphatic aldehydes is demonstrated. This protocol allows access to branched ketones from readily available materials in an atom-economical manner. The quadruple catalysis can transfer a formyl hydrogen of aldehydes as a hydrogen radical equivalent onto the terminal carbon of an alkene by controlled electron and proton transfers.

A Triple Photoredox/Cobalt/Brønsted Acid Catalysis Enabling Markovnikov Hydroalkoxylation of Unactivated Alkenes.

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) complex to alkyl Co(IV). The precise control of protons and electrons by the three catalysts allows the elimination of strong acids and external reductants/oxidants that are required in the conventional methods.

Catalytic Reductive Cross-Coupling between Aromatic Aldehydes and Arylnitriles.

A reductive cross-coupling reaction between aromatic aldehydes and arylnitriles using a copper catalyst and a silylboronate as a reductant is reported. This protocol represents an unprecedented approach to the chemoselective synthesis of α-hydroxy ketones by electrophile-electrophile cross-coupling.

Fluorescent-Oxaboroles: Synthesis and Optical Property by Sugar Recognition.

The optical property of fluorescent unit-conjugated aliphatic oxaboroles has been investigated. The oxaboroles provide good fluorescence quantum yields and selective recognition toward D-ribose and D-ribose containing molecules. The molecular recognition induced significant fluorescence quenching. The property of the boroles showed the possibility of the boron-based nicotinamide adenine dinucleotide (NAD) sensor probe.

Organophotoredox-Catalyzed Decarboxylative C(sp3)-O Bond Formation.

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.

Transition-Metal-Free Cross-Coupling by Using Tertiary Benzylic Organoboronates.

The transition-metal-free cross-coupling of alkyl or aryl electrophiles by using tertiary benzylic organoboronates is reported. This reaction involves the generation of tertiary alkyl anions from organoboronates in the presence of an alkoxide base and then their substitution reactions. This protocol allows the simple and efficient construction of quaternary carbon centers.

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions.

The allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions is described. The synergistic palladium/copper-catalyzed reaction of aromatic aldehydes, allylic carbonates, and a silylboronate produces the corresponding homoallylic alcohol derivatives. This process involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(I) species and the subsequent palladium-catalyzed allylic substitution.

N-Heterocyclic Carbene-Catalyzed Radical Relay Enabling Vicinal Alkylacylation of Alkenes.

The N-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 addition of the resultant alkyl radical to the alkene followed by radical-radical coupling.

N-Heterocyclic Carbene-Catalyzed Decarboxylative Alkylation of Aldehydes.

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 enolate form of Breslow intermediate to a redox ester followed by recombination of the resultant radical pair to form a carbon-carbon bond is proposed.

Reductive Coupling between Aromatic Aldehydes and Ketones or Imines by Copper Catalysis.

The copper-catalyzed reductive coupling of two different carbonyl compounds has been achieved. The reaction of aromatic aldehydes and arylketones with a silylboronate in the presence of a catalytic amount of a CuCl-N-heterocyclic carbene (NHC) complex and a stoichiometric amount of alkoxide base yielded cross-coupled 1,2-diol derivatives. A reaction pathway is proposed that involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(I) species from the aromatic aldehyde and its subsequent coupling with the arylketone. This process was amenable to asymmetric catalysis. This copper catalyst system also enabled the reductive coupling between aromatic aldehydes and imines.

Asymmetric Catalysis Using Aromatic Aldehydes as Chiral α-Alkoxyalkyl Anions.

We have developed a new umpolung strategy for catalytically forming a chiral α-alkoxyalkyl anion from an aromatic aldehyde for use in asymmetric synthesis. The reaction between aromatic aldehydes and aryl or allyl electrophiles with a silylboronate utilizing a chiral copper-N-heterocyclic carbene catalyst and a palladium-bisphosphine catalyst in a synergistic manner occurred with high enantioselectivities to deliver the three-component coupling products, chiral silyl-protected secondary alcohol derivatives. Our method features the catalytic generation of enantioenriched chiral α-alkoxyalkylcopper(I) intermediates from aldehydes and their subsequent palladium-catalyzed stereospecific cross-coupling.

Dehydrative Allylation between Aldehydes and Allylic Alcohols through Synergistic N-Heterocyclic Carbene/Palladium Catalysis.

Dehydrative allylation between widely available aldehydes and allylic alcohols to afford ß,γ-unsaturated ketones was enabled by a synergistic merger of a thiazolium N-heterocyclic carbene catalyst and a palladium-bisphosphine catalyst.

Phosphine-Catalyzed anti-Carboboration of Alkynoates with 9-BBN-Based 1,1-Diborylalkanes: Synthesis and Use of Multisubstituted γ-Borylallylboranes.

Trialkylphosphine organocatalysis has enabled the regioselective anti-carboboration of alkynoates with 9-BBN-based 1,1-diborylalkanes to produce secondary allylboranes with ß-alkoxycarbonyl and γ-boryl substituents. The utility of the densely functionalized allylboranes was demonstrated by the highly diastereoselective allylation of N-(trimethylsilyl)aldimines to produce homoallylamines containing tertiary allylborane and acrylate moieties.

Copper-Catalyzed γ-Selective and Stereospecific Allylic Cross-Coupling with Secondary Alkylboranes.

The scope of the copper-catalyzed coupling reactions between organoboron compounds and allylic phosphates is expanded significantly by employing triphenylphosphine as a ligand for copper, allowing the use of secondary alkylboron compounds. The reaction proceeds with complete γ-E-selectivity and preferential 1,3-syn stereoselectivity. The reaction of γ-silicon-substituted allylic phosphates affords enantioenriched α-stereogenic allylsilanes.

Synthesis of 1,1-Diborylalkenes through a Brønsted Base Catalyzed Reaction between Terminal Alkynes and Bis(pinacolato)diboron.

A method for the synthesis of 1,1-diborylalkenes through a Brønsted base catalyzed reaction between terminal alkynes and bis(pinacolato)diboron has been developed. The procedure allows direct synthesis of functionalized 1,1-diborylalkenes from various terminal alkynes including propiolates, propiolamides, and 2-ethynylazoles.

Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates.

A copper-catalyzed conjugate addition of alkylboron compounds (alkyl-9-BBN, prepared by hydroboration of alkenes with 9-BBN-H) to alkynoates to form ß-disubstituted acrylates is reported. The addition occurred in a formal syn-hydroalkylation mode. The syn stereoselectivity was excellent regardless of the substrate structure. A variety of functional groups were compatible with the conjugate addition.

Phosphine-catalyzed anti-carboboration of alkynoates with alkyl-, alkenyl-, and arylboranes.

We found that trialkylphosphine organocatalysts promoted unprecedented anti-carboboration of alkynoates with alkyl-, alkenyl-, or arylboranes to form ß-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 ß carbon atom. The regioselectivity and the anti stereoselectivity were both complete and robust. In addition, the substrate scope was broad with excellent functional group compatibility.

Synthesis of trisubstituted alkenylstannanes through copper-catalyzed three-component coupling of alkylboranes, alkynoates, and tributyltin methoxide.

A versatile route to trisubstituted alkenylstannanes is presented. The alkyl and Sn moieties were introduced at the ß and α carbon atoms of alkynoates, respectively, in a formal syn addition mode with complete regioselectivity. A variety of functional groups were tolerated in the alkylboranes and alkynoates.

Biomimetic design of an α-ketoacylphosphonium-based light-activated oxygenation auxiliary.

The biomimetic design of a transition metal complex based on the iron(iv)-oxo porphyrin π-cation radical species in cytochrome P450 enzymes has been studied extensively. Herein, we translate the functions of this iron(iv)-oxo porphyrin π-cation radical species to an α-ketoacyl phosphonium species comprised of non-metal atoms and utilize it as a light-activated oxygenation auxiliary for ortho-selective oxygenation of anilines. Visible light irradiation converts the α-ketoacyl phosphonium species to the excited state, which acts as a transiently generated oxidant. The intramolecular nature of the process ensures high regioselectivity and chemoselectivity. The auxiliary is easily removable. A one-pot protocol is also described.