Iridium‐Catalyzed Enantioselective Allyl–Allylsilane Cross‐Coupling

An enantioselective allyl–allylsilane cross‐coupling involving racemic branched allylic alcohols and allylsilanes is reported. An iridium‐(P,olefin) phosphoramidite complex enables the transformation with high regio‐ and stereoselectivity under operationally simple conditions. The utility of the coupling is demonstrated in a concise catalytic, enantioselective synthesis of a pyrethroid insecticide protrifenbute.     

Aromatic Chemistry in the Excited State: Facilitating Metal‐Free Substitutions and Cross‐Couplings

Transition‐metal‐catalyzed cross‐couplings between aromatic electrophiles and nucleophiles have revolutionized modern chemical syntheses. Nevertheless, transition‐metal‐free approaches are preferable, considering the various issues caused by metal catalysts. This Minireview summarizes the recent progress in the light‐enabled transition‐metal‐free formation of carbon–carbon and carbon–heteroatom bonds in aromatics, which opens a new avenue in aromatic reactions. From the mechanistic perspective, it classifies different reaction types of aryl electrophiles in an excited state with various nucleophiles. We believe this will provide more rationales for metal‐free aromatic substitutions and cross‐couplings with light, and guide the development of novel transformations of aromatic compounds facilitated by light.     

Copper‐Catalyzed Borylative Allyl–Allyl Coupling Reaction

Borylative allyl–allyl coupling using allenes, bis(pinacolato)diboron, and allyl phosphates has been developed in the presence of a copper catalyst bearing an N‐heterocyclic carbene ligand. The reaction affords boryl‐substituted 1,5‐diene derivatives in good to high yields with high regioselectivity and Z selectivity.     

Transition‐Metal‐Free C(sp2)–C(sp2) Cross‐Coupling of Diazo Quinones with Catechol Boronic Esters

A transition‐metal‐free C(sp²)?C(sp²) bond formation reaction by the cross‐coupling of diazo quinones with catechol boronic esters was developed. With this protocol, a variety of biaryls and alkenyl phenols were obtained in good to high yields under mild conditions. The reaction tolerates various functionalities and is applicable to the derivatization of pharmaceuticals and natural products. The synthetic utility of the method was demonstrated by the short synthesis of multi‐substituted triphenylenes and three bioactive natural products, honokiol, moracin M, and stemofuran A. Mechanistic studies and density functional theory (DFT) calculations revealed that the reaction involves attack of the boronic ester by a singlet quinone carbene followed by a 1,2‐rearrangement through a stepwise mechanism.     

Transition‐Metal‐Free Borylation of Allylic and Propargylic Alcohols

The base‐catalyzed allylic borylation of tertiary allylic alcohols allows the synthesis of 1,1‐disubstituted allyl boronates, in moderate to high yield. The unexpected tandem performance of the Lewis acid–base adduct, [Hbase]⁺[MeO‐B₂pin₂]^? favored the formation of 1,2,3‐triborylated species from the tertiary allylic alcohols and 1‐propargylic cyclohexanol at 90 °C.     

Synthesis of Heterocycles through Transition‐Metal‐Catalyzed Isomerization Reactions

Metal‐catalyzed isomerization of N‐ and O‐allylic systems is emerging as an effective method to form synthetically useful iminium and oxocarbenium intermediates. In the presence of tethered nucleophiles, several recent examples illuminate this approach as a powerful strategy for the synthesis of structurally complex and diverse heterocycles. In this Concept article, we attempt to cover this area of research through a selection of recent versatile examples.     

Copper‐Catalyzed Enantioselective Allyl–Allyl Coupling between Allylic Boronates and Phosphates with a Phenol/N‐Heterocyclic Carbene Chiral Ligand

Copper‐catalyzed enantioselective allyl–allyl coupling between allylboronates and either Z‐acyclic or cyclic allylic phosphates using a new chiral N‐heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional S_N2′‐type regioselectivities and high enantioselectivities to deliver chiral 1,5‐diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position.     

Transition‐Metal‐Free BF3‐Mediated Oxidative and Non‐Oxidative Cross‐Coupling of Pyridines

We report a BF₃‐mediated direct alkynylation of pyridines at C(2) by using a variety of alkynyllithium reagents (oxidative cross‐coupling). Moreover, we have developed a novel transition‐metal‐free cross‐coupling method between alkylmagnesium reagents and 4‐substituted pyridines, such as isonicotinonitrile and 4‐chloropyridine, by employing BF₃?OEt₂ as a promoter. The combination of these methods enabled us to efficiently prepare a range of di‐, tri‐, and tetrasubstituted pyridines.     

A Transition‐Metal‐Free Synthesis of Fluorinated Naphthols

Herein, we describe a transition‐metal‐free protocol for the conversion of simple 2‐allyl‐3‐(trifluoromethyl)phenols into substituted 5‐fluoronaphthalen‐1‐ols. The key events of this reaction include the selective activation of two C?F bonds and formation of an intermediate hexatriene system, which undergoes a 6π electrocyclization, followed by rearomatization. This concept enables the rapid conversion (three steps) of various commercially available 3‐(trifluoromethyl)phenols into novel fluorine‐containing naphthols, which are difficult to prepare by previous methods. The reported sequence was also extended to a one‐pot transformation of 3‐(trifluoromethyl)phenols into 5‐fluoronaphthalen‐1‐ols.     

Direct Cross‐Couplings of Propargylic Diols

[Pd(PPh₃)₄] catalyzes a Suzuki–Miyaura‐like twofold cross‐coupling sequence between underivatized propargylic diols and either aryl or alkenyl boronic acids to furnish highly substituted 1,3‐dienes. Thus, 2,3‐diaryl‐1,3‐butadienes and their dialkenic congeners ([4]dendralenes) are delivered in a (pseudo)halogen‐free, single‐step synthesis which supersedes existing methods. Allenols are also readily formed. Treatment of these single‐ and twofold cross‐coupled products with acid leads to remarkably short syntheses of highly‐substituted benzofulvenes and aryl indenes, respectively.     

Functionalization of Hydrogenated Graphene: Transition‐Metal‐Catalyzed Cross‐Coupling Reactions of Allylic C−H Bonds

The chemical functionalization of hydrogenated graphene can modify its physical properties and lead to better processability. Herein, we describe the chemical functionalization of hydrogenated graphene through a dehydrogenative cross‐coupling reaction between an allylic C?H bond and the α‐C?H bond of tetrahydrothiophen‐3‐one using Cu(OTf)₂ as the catalyst and DDQ as the oxidant. The chemical functionalization was confirmed by X‐ray photoelectron spectroscopy and Fourier transform infrared spectroscopy and visualized by scanning electron microscopy. The functionalized hydrogenated graphene material demonstrated improved dispersion stability in water, bringing new quality to the elusive hydrogenated graphene (graphane) materials. Hydrogenated graphene provides broad possibilities for chemical modifications owing to its reactivity.     

Sulfur(IV)‐Mediated Unsymmetrical Heterocycle Cross‐Couplings

Despite the tremendous utilities of metal‐mediated cross‐couplings in modern organic chemistry, coupling reactions involving nitrogenous heteroarenes remain a challenging undertaking – coordination of Lewis basic atoms into metal centers often necessitate elevated temperature, high catalyst loading, etc. Herein, we report a sulfur (IV) mediated cross‐coupling amendable for the efficient synthesis of heteroaromatic substrates. Addition of heteroaryl nucleophiles to a simple, readily‐accessible alkyl sulfinyl (IV) chloride allows formation of a trigonal bipyramidal sulfurane intermediate. Reductive elimination therefrom provides bis‐heteroaryl products in a practical and efficient fashion.     

Transition‐Metal‐Free Oxidative Cross‐Coupling of Tetraarylborates to Biaryls Using Organic Oxidants

Readily prepared tetraarylborates undergo selective (cross)‐coupling through oxidation with Bobbitt's salt to give symmetric and unsymmetric biaryls. The organic oxoammonium salt can be used either as a stoichiometric oxidant or as a catalyst in combination with in situ generated NO₂ and molecular oxygen as the terminal oxidant. For selected cases, oxidative coupling is also possible with NO₂/O₂ without any additional nitroxide‐based cocatalyst. Transition‐metal‐free catalytic oxidative ligand cross‐coupling of tetraarylborates is unprecedented and the introduced method provides access to various biaryl and heterobiaryl systems.     

Stereoselective Csp3−Csp2 Cross‐Couplings of Chiral Secondary Alkylzinc Reagents with Alkenyl and Aryl Halides

We report palladium‐catalyzed cross‐coupling reactions of chiral secondary non‐stabilized dialkylzinc reagents, prepared from readily available chiral secondary alkyl iodides, with alkenyl and aryl halides. This method provides α‐chiral alkenes and arenes with very high retention of configuration (dr up to 98:2) and satisfactory overall yields (up to 76 % for 3 reaction steps). The configurational stability of these chiral non‐stabilized dialkylzinc reagents was determined and exceeded several hours at 25 °C. DFT calculations were performed to rationalize the stereoretention during the catalytic cycle. Furthermore, the cross‐coupling reaction was applied in an efficient total synthesis of the sesquiterpenes (S)‐ and (R)‐curcumene with control of the absolute stereochemistry.     

Integrating Allyl Electrophiles into Nickel‐Catalyzed Conjunctive Cross‐Coupling

Allylation and conjunctive cross‐coupling represent two useful, yet largely distinct, reactivity paradigms in catalysis. The union of these two processes would offer exciting possibilities in organic synthesis but remains largely unknown. Herein, we report the use of allyl electrophiles in nickel‐catalyzed conjunctive cross‐coupling with a non‐conjugated alkene and dimethylzinc. The transformation is enabled by weakly coordinating, monodentate aza‐heterocycle directing groups that are useful building blocks in synthesis, including saccharin, pyridones, pyrazoles, and triazoles. The reaction occurs under mild conditions and is compatible with a wide range of allyl electrophiles. High chemoselectivity through substrate directivity is demonstrated by the facile reactivity of the β‐γ alkene of the starting material, whereas the ?‐ζ alkene of the product is preserved. The generality of this approach is further illustrated through the development of an analogous method with alkyne substrates. Mechanistic studies reveal the importance of the dissociation of the weakly coordinating directing group to allow the allyl moiety to bind and facilitate C(sp³)?C(sp³) reductive elimination.     

Reagent‐ and Metal‐Free Anodic C−C Cross‐Coupling of Aniline Derivatives

The dehydrogenative cross‐coupling of aniline derivatives to 2,2′‐diaminobiaryls is reported. The oxidation is carried out electrochemically, which avoids the use of metals and reagents. A large variety of biphenyldiamines were thus prepared. The best results were obtained when glassy carbon was used as the anode material. The electrosynthetic reaction is easily performed in an undivided cell at slightly elevated temperature. In addition, common amine protecting groups based on carboxylic acids were employed that can be selectively removed under mild conditions after the cross‐coupling, which provides quick and efficient access to important building blocks featuring free amine moieties.     

Electrochemical Synthesis of Thienoacene Derivatives: Transition‐Metal‐Free Dehydrogenative C−S Coupling Promoted by a Halogen Mediator

The first electrochemical dehydrogenative C?S bond formation leading to thienoacene derivatives is described. Several thienoacene derivatives were synthesized by dehydrogenative C?H/S?H coupling. The addition of ⁿBu₄NBr, which catalytically promoted the reaction as a halogen mediator, was essential.