Selective 1,2-Aryl-Aminoalkylation of Alkenes Enabled by Metallaphotoredox Catalysis

A highly chemo- and regioselective intermolecular 1,2-aryl-aminoalkylation of alkenes by photoredox/nickel dual catalysis is described here. This three-component conjunctive cross-coupling is highlighted by its first application of primary alkyl radicals, which were not compatible in previous reports. The readily prepared α-silyl amines could be transferred to α-amino radicals by photo-induced single electron transfer step. The radical addition/cross-coupling cascade reaction proceeds under mild, base-free and redox-neutral conditions with good functional group tolerance, and importantly, provides an efficient and concise method for the synthesis of structurally valuable α-aryl substituted γ-amino acid derivatives motifs.     

Decarboxylative Conjunctive Cross‐coupling of Vinyl Boronic Esters using Metallaphotoredox Catalysis

The synthesis of complex alkyl boronic esters through conjunctive cross‐coupling of vinyl boronic esters with carboxylic acids and aryl iodides is described. The reaction proceeds under mild metallaphotoredox conditions and involves an unprecedented decarboxylative radical addition/cross‐coupling cascade of vinyl boronic esters. Excellent functional‐group tolerance is displayed, and application of a range of carboxylic acids, including secondary α‐amino acids, and aryl iodides provides efficient access to highly functionalized alkyl boronic esters. The decarboxylative conjunctive cross‐coupling was also applied to the synthesis of sedum alkaloids.     

Gold‐Catalyzed 1,2‐Diarylation of Alkenes

Herein, we disclose the gold‐catalyzed 1,2‐diarylation of alkenes through the interplay of ligand‐enabled Au^I/Au^III catalysis with the idiosyncratic π‐activation mode of gold complexes. Unlike the classical migratory‐insertion‐based approach to 1,2‐diarylation, the present approach not only circumvents the formation of direct Ar?Ar′ coupling and Heck‐type side products but more intriguingly demonstrates reactivity and selectivity complementary to those of previously known metal catalysis (Pd, Ni, or Cu). Detailed investigations to underpin the mechanistic scenario revealed oxidative addition of aryl iodides to an Au^I complex to be the rate‐limiting step owing to the non‐innocent nature of the aryl alkene.     

Gold-Catalyzed 1,2-Diarylation of Alkenes

Herein, we disclose the gold-catalyzed 1,2-diarylation of alkenes through the interplay of ligand-enabled Au^I/Au^III catalysis with the idiosyncratic π-activation mode of gold complexes. Unlike the classical migratory-insertion-based approach to 1,2-diarylation, the present approach not only circumvents the formation of direct Ar−Ar′ coupling and Heck-type side products but more intriguingly demonstrates reactivity and selectivity complementary to those of previously known metal catalysis (Pd, Ni, or Cu). Detailed investigations to underpin the mechanistic scenario revealed oxidative addition of aryl iodides to an Au^I complex to be the rate-limiting step owing to the non-innocent nature of the aryl alkene.     

Site‐Selective 1,2‐Dicarbofunctionalization of Vinyl Boronates through Dual Catalysis

A modular, site‐selective 1,2‐dicarbofunctionalization of vinyl boronates with organic halides through dual catalysis is described. This reaction proceeds under mild conditions and is characterized by excellent chemo‐ and regioselectivity. It thus represents a complementary new technique for preparing densely functionalized alkyl boron architectures from simple and accessible precursors.     

Nickel‐Catalyzed Asymmetric Reductive 1,2‐Carboamination of Unactivated Alkenes

Starting from diverse alkene‐tethered aryl iodides and O‐benzoyl‐hydroxylamines, the enantioselective reductive cross‐electrophilic 1,2‐carboamination of unactivated alkenes was achieved using a chiral pyrox/nickel complex as the catalyst. This mild, modular, and practical protocol provides rapid access to a variety of β‐chiral amines with an enantioenriched aryl‐substituted quaternary carbon center in good yields and with excellent enantioselectivities. This process reveals a complementary regioselectivity when compared to Pd and Cu catalysis.     

Transition-Metal-Free Three-Component Radical 1,2-Amidoalkynylation of Unactivated Alkenes

A transition-metal-free radical 1,2-amidoalkynylation of unactivated alkenes is presented. α-Amido-oxy acids were used as amidyl radical precursors, which were oxidized by an organic photoredox catalyst (4CzlPN). The electrophilic N-radicals chemoselectively reacted with various aliphatic alkenes and the adduct radicals were then trapped by ethynylbenziodoxolone (EBX) reagents to eventually provide the amidoalkynylation products. These transformations, which were conducted under practical and mild conditions, showed high functional group tolerance and broad substrate scope. Mechanistic studies supported the radical nature of these cascades.     

Alkene Isomerization–Hydroarylation Tandem Catalysis: Indole C2‐Alkylation with Aryl‐Substituted Alkenes Leading to 1,1‐Diarylalkanes

A cobalt‐N‐heterocyclic carbene catalyst generated from CoBr₂, imidazolium salt, and cyclohexylmagnesium bromide was found to promote the imine‐directed C2‐alkylation of indoles with nonconjugated arylalkenes through a tandem alkene isomerization–hydroarylation process, affording 1,1‐diarylalkanes with exclusive regioselectivity. The feasibility of the tandem catalysis was demonstrated for allyl‐, homoallyl‐, and bishomoallylbenzene derivatives. The catalytic system is also applicable to a variety of β‐substituted styrene derivatives. Mechanistic experiments using deuterium‐labeled indole substrate and Grignard reagent provided insight into the cobalt‐mediated C? H activation step, which likely involves exchange of the C2‐hydrogen atom of the former and the β‐hydrogen atoms of the latter.     

Ligand‐Enabled Nickel‐Catalyzed Redox‐Relay Migratory Hydroarylation of Alkenes with Arylborons

A redox‐relay migratory hydroarylation of isomeric mixtures of olefins with arylboronic acids catalyzed by nickel complexes bearing diamine ligands is described. A range of structurally diverse 1,1‐diarylalkanes, including those containing a 1,1‐diarylated quaternary carbon, were obtained in excellent yields and with high regioselectivity. Preliminary experimental evidence supports the proposed non‐dissociated chainwalking of aryl‐nickel(II)‐hydride species along the alkyl chain of alkenes before selective reductive elimination at a benzylic position. A catalyst loading as low as 0.5 mol % proved to be sufficient in large‐scale synthesis while retaining high reactivity, highlighting the practical value of this transformation.     

Stereospecific 1,2‐Migrations of Boronate Complexes Induced by Electrophiles

The stereospecific 1,2‐migration of boronate complexes is one of the most representative reactions in boron chemistry. This process has been used extensively to develop powerful methods for asymmetric synthesis, with applications spanning from pharmaceuticals to natural products. Typically, 1,2‐migration of boronate complexes is driven by displacement of an α‐leaving group, oxidation of an α‐boryl radical, or electrophilic activation of an alkenyl boronate complex. The aim of this article is to summarize the recent advances in the rapidly expanding field of electrophile‐induced stereospecific 1,2‐migration of groups from boron to sp² and sp³ carbon centers. It will be shown that three different conceptual approaches can be utilized to enable the 1,2‐migration of boronate complexes: stereospecific Zweifel‐type reactions, catalytic conjunctive coupling reactions, and transition metal‐free sp²–sp³ couplings. A discussion of the reaction scope, mechanistic insights, and synthetic applications of the work described is also presented.     

Stereoselective Synthesis of Polysubstituted Alkenes through a Phosphine‐Mediated Three‐Component System of Aldehydes, α‐Halo Carbonyl Compounds,and Terminal Alkenes

Geometrical control : PPh₃ and methyl acrylate (or acrylamide) are able to mediate the one‐pot Wittig reaction of aldehydes with α‐halo carbonyl compounds for the synthesis of 1,2‐disubstituted and trisubstituted alkenes in an excellent stereoselective fashion. Furthermore, the first one‐pot, three‐component reaction of aldehydes, α‐halo acetates, and terminal alkenes has been developed in the presence of PPh₃ to produce trisubstituted alkenes with excellent E selectivity (see scheme).

     

Pseudo‐Stereodivergent Synthesis of Enantioenriched Tetrasubstituted Alkenes by Cascade 1,3‐Oxo‐Allylation/Cope Rearrangement

The catalytic diastereodivergent construction of stereoisomers having two or more stereogenic centers has been extensively studied. In contrast, the switchable introduction of another stereogenic element, that is, Z/E configuration involving a polysubstituted alkene group, into the optically active stereoisomers, has not been recognized yet. Disclosed here is the pseudo‐stereodivergent synthesis of highly enantioenriched tetrasubstituted alkene architectures from isatin‐based Morita–Baylis–Hillman carbonates and allylic derivatives, under the cooperative catalysis of a tertiary amine and a chiral iridium complex. The success of the switchable construction of the tetrasubstituted alkene motif relies on the diastereodivergent 1,3‐oxo‐allylation reaction between N‐allylic ylides and chiral π‐allyliridium complex intermediates by ligand and substrate control, followed by the stereoselective concerted 3,3‐Cope rearrangement process.     

Selective ortho‐Functionalization of Adamantylarenes Enabled by Dispersion and an Air‐Stable Palladium(I) Dimer

Contrary to the general belief that Pd‐catalyzed cross‐coupling at sites of severe steric hindrance are disfavored, we herein show that the oxidative addition to C?Br ortho to an adamantyl group is as favored as the corresponding adamantyl‐free system due to attractive dispersion forces. This enabled the development of a fully selective arylation and alkylation of C?Br ortho to an adamantyl group, even if challenged with competing non‐hindered C?OTf or C?Cl sites. The method makes use of an air‐stable Pd^I dimer and enables straightforward access to diversely substituted therapeutically important adamantylarenes in 5–30 min.     

Reduction of Activated Alkenes by PIII/PV Redox Cycling Catalysis

The carbon–carbon double bond of unsaturated carbonyl compounds was readily reduced by using a phosphetane oxide catalyst in the presence of a simple organosilane as the terminal reductant and water as the hydrogen source. Quantitative hydrogenation was observed when 1.0 mol % of a methyl‐substituted phosphetane oxide was employed as the catalyst. The procedure is highly selective towards activated double bonds, tolerating a variety of functional groups that are usually prone to reduction. In total, 25 alkenes and two alkynes were hydrogenated to the corresponding alkanes in excellent yields of up to 99 %. Notably, less active poly(methylhydrosiloxane) could also be utilized as the terminal reductant. Mechanistic investigations revealed the phosphane as the catalyst resting state and a protonation/deprotonation sequence as the crucial step in the catalytic cycle.     

Highly Chemo‐, Regio‐, and Enantioselective Rhodium‐Catalyzed Cross‐Cyclotrimerization of Two Different Alkynes with Alkenes

It has been established that a cationic rhodium(I)/(R)‐tol‐binap complex catalyzes the cross‐cyclotrimerization of silylacetylenes, di‐tert‐butyl acetylenedicarboxylates, and acrylamides with excellent chemo‐, regio‐, and enantioselectivities. Unsymmetrical alkynoates can also be employed in place of di‐tert‐butyl acetylenedicarboxylate for this process, but with reduced chemoselectivity.     

Aerobic Palladium‐Catalyzed Dioxygenation of Alkenes Enabled by Catalytic Nitrite

Catalytic nitrite was found to enable carbon–oxygen bond‐forming reductive elimination from unstable alkyl palladium intermediates, providing dioxygenated products from alkenes. A variety of functional groups were tolerated, and high yields (up to 94 %) were observed with many substrates, also for a multigram‐scale reaction. Nitrogen dioxide, which could form from nitrite under the reaction conditions, was demonstrated to be a potential intermediate in the catalytic cycle. Furthermore, the reductive elimination event was probed with ¹⁸O‐labeling experiments, which demonstrated that both oxygen atoms in the difunctionalized products were derived from one molecule of acetic acid.     

Zirconium‐Catalyzed Atom‐Economical Synthesis of 1,1‐Diborylalkanes from Terminal and Internal Alkenes

A general and atom‐economical synthesis of 1,1‐diborylalkanes from alkenes and a borane without the need for an additional H₂ acceptor is reported for the first time. The key to our success is the use of an earth‐abundant zirconium‐based catalyst, which allows a balance of self‐contradictory reactivities (dehydrogenative boration and hydroboration) to be achieved. Our method avoids using an excess amount of another alkene as an H₂ acceptor, which was required in other reported systems. Furthermore, substrates such as simple long‐chain aliphatic alkenes that did not react before also underwent 1,1‐diboration in our system. Significantly, the unprecedented 1,1‐diboration of internal alkenes enabled the preparation of 1,1‐diborylalkanes.     

Direct Catalytic Synthesis of Unprotected 2‐Amino‐1‐Phenylethanols from Alkenes by Using Iron(II) Phthalocyanine

Aryl‐substituted amino alcohols are privileged scaffolds in medicinal chemistry and natural products. Herein, we report that an exceptionally simple and inexpensive Fe^II complex efficiently catalyzes the direct transformation of simple alkenes into unprotected amino alcohols in good yield and perfect regioselectivity. This new catalytic method was applied in the expedient synthesis of bioactive molecules and could be extended to aminoetherification.