Spirobipyridine Ligand Enabled Iridium-Catalyzed Site-Selective C-H Activation via Non-Covalent Interactions.

The selective borylation of specific C-H bonds in organic synthesis remains a formidable challenge. In this study, we present a novel spirobipyridine ligand that features a binaphthyl backbone. This ligand facilitates the iridium-catalyzed selective C-H borylation of benzene derivatives. The ligand is designed with "side-arm-wall" substituents that allow vicinal di- or multi-substituted benzene derivatives to approach metal center and effectively block other reactive sites by non-covalent interactions with substrates. The effectiveness of this strategy is demonstrated by the successful selective distal C-H activation of various alkaloids and its broad compatibility with functional groups.

Photoinduced Nickel-Catalyzed Carbon-Heteroatom Coupling.

Herein, we report visible light-promoted single nickel catalysis for diverse carbon-heteroatom couplings under mild conditions. This mild, general, and robust method to couple diverse nitrogen, oxygen, and sulfur nucleophiles with aryl(heteroaryl)/alkenyl iodides/bromides exhibits a wide functional group tolerance and is applicable to late-stage modification of pharmaceuticals and natural products. On the base of preliminary mechanistic studies, a NiI /NiIII cycle via the generation of active NiI complexes that appear from homolysis of NiII -I rather than NiII -aryl bond was tentatively proposed.

Cobalt(III)/Chiral Carboxylic Acid-Catalyzed Enantioselective Synthesis of Benzothiadiazine-1-oxides via C-H Activation.

Among sulfoximine derivatives containing a chiral sulfur center, benzothiadiazine-1-oxides are important for applications in medicinal chemistry. Here, we report that the combination of an achiral cobalt(III) catalyst and a pseudo-C2 -symmetric H8 -binaphthyl chiral carboxylic acid enables the asymmetric synthesis of benzothiadiazine-1-oxides from sulfoximines and dioxazolones via enantioselective C-H bond cleavage. With the optimized protocol, benzothiadiazine-1-oxides with several functional groups can be accessed with high enantioselectivity.

Photocatalytic Generation of π-Allyltitanium Complexes via Radical Intermediates.

The addition of π-allylmetal complexes to carbonyls is the most important route to homoallylic alcohols. This study reports the first photocatalytic generation of π-allyltitanium complexes by a radical strategy. This novel strategy enables the three-component allylation of carbonyls with 1,3-butadiene, providing rapid access to valuable homoallylic alcohols (over 60 examples). The exceptional regio- and diastereoselectivity provided by dual photoredox/Ti catalysis is comparable to that of the Cr-catalyzed Nozaki-Hiyama-Kishi allylation reaction.

Chiral Carboxylic Acid Enabled Achiral Rhodium(III)-Catalyzed Enantioselective C-H Functionalization.

Reported is an achiral Cpx RhIII /chiral carboxylic acid catalyzed asymmetric C-H alkylation of diarylmethanamines with a diazomalonate, followed by cyclization and decarboxylation to afford 1,4-dihydroisoquinolin-3(2H)-one. Secondary alkylamines as well as nonprotected primary alkylamines underwent the transformation with high enantioselectivities (up to 98.5:1.5 e.r.) by using a newly developed chiral carboxylic acid as the sole source of chirality to achieve enantioselective C-H cleavage by a concerted metalation-deprotonation mechanism.

Palladium-Catalyzed Long-Range Deconjugative Isomerization of Highly Substituted α,ß-Unsaturated Carbonyl Compounds.

The long-range deconjugative isomerization of a broad range of α,ß-unsaturated amides, esters, and ketones by an in situ generated palladium hydride catalyst is described. This redox-economical process is triggered by a hydrometalation event and is thermodynamically driven by the refunctionalization of a primary or a secondary alcohol into an aldehyde or a ketone. Di-, tri-, and tetrasubstituted carbon-carbon double bonds react with similar efficiency; the system is tolerant toward a variety of functional groups, and olefin migration can be sustained over 30 carbon atoms. The refunctionalized products are usually isolated in good to excellent yield. Mechanistic investigations are in support of a chain-walking process consisting of repeated migratory insertions and ß-H eliminations. The bidirectionality of the isomerization reaction was established by isotopic labeling experiments using a substrate with a double bond isolated from both terminal functions. The palladium hydride was also found to be directly involved in the product-forming tautomerization step. The ambiphilic character of the in situ generated [Pd-H] was demonstrated using isomeric trisubstituted α,ß-unsaturated esters. Finally, the high levels of enantioselectivity obtained in the isomerization of a small set of α-substituted α,ß-unsaturated ketones augur well for the successful development of an enantioselective version of this unconventional isomerization.

Catalytic Asymmetric Iterative/Domino Aldehyde Cross-Aldol Reactions for the Rapid and Flexible Synthesis of 1,3-Polyols.

We report here catalytic asymmetric iterative and domino cross-aldol reactions between aldehydes, endowed with a high level of robustness, flexibility, and generality. A Cu(I)-DTBM-SEGPHOS complex catalyzes an asymmetric cross-aldol reaction between acceptor aldehydes and boron enolates derived from donor aldehydes, which are generated through Ir-catalyzed isomerization of allyloxyboronates. The unit process can be repeated using the aldol products in turn as acceptor substrates for the subsequent asymmetric aldol reaction. The donor aldehydes and stereoselectivity can be flexibly switched in a stepwise manner for the double-aldol reaction. Furthermore, asymmetric triple- and quadruple-aldol reactions are possible in one-pot using the appropriate amounts of donors and amine additives, rapidly elongating the carbon skeleton with controlling up to eight stereocenters. The method should be useful for straightforward synthesis of enantiomerically and diastereomerically enriched 1,3-polyols.

Scope and mechanism in palladium-catalyzed isomerizations of highly substituted allylic, homoallylic, and alkenyl alcohols.

Herein we report the palladium-catalyzed isomerization of highly substituted allylic alcohols and alkenyl alcohols by means of a single catalytic system. The operationally simple reaction protocol is applicable to a broad range of substrates and displays a wide functional group tolerance, and the products are usually isolated in high chemical yield. Experimental and computational mechanistic investigations provide complementary and converging evidence for a chain-walking process consisting of repeated migratory insertion/ß-H elimination sequences. Interestingly, the catalyst does not dissociate from the substrate in the isomerization of allylic alcohols, whereas it disengages during the isomerization of alkenyl alcohols when additional substituents are present on the alkyl chain.

In situ copper photocatalysts triggering halide atom transfer of unactivated alkyl halides for general C(sp3)-N couplings.

Direct reduction of unactivated alkyl halides for C(sp3)-N couplings under mild conditions presents a significant challenge in organic synthesis due to their low reduction potential. Herein, we introduce an in situ formed pyridyl-carbene-ligated copper (I) catalyst that is capable of abstracting halide atom and generating alkyl radicals for general C(sp3)-N couplings under visible light. Control experiments confirmed that the mono-pyridyl-carbene-ligated copper complex is the active species responsible for catalysis. Mechanistic investigations using transient absorption spectroscopy across multiple decades of timescales revealed ultrafast intersystem crossing (260 ps) of the photoexcited copper (I) complexes into their long-lived triplet excited states (>2 µs). The non-Stern-Volmer quenching dynamics of the triplets by unactivated alkyl halides suggests an association between copper (I) complexes and alkyl halides, thereby facilitating the abstraction of halide atoms via inner-sphere single electron transfer (SET), rather than outer-sphere SET, for the formation of alkyl radicals for subsequent cross couplings.

Photoinduced Homolysis of the Ni-P Bond via Ligand to Metal Charge Transfer for C-P Bond Formation in Nickel Catalysis.

Photoinduced homolysis of NiII-carbon and -heteroatom bonds has been well studied for carbon-heteroatom couplings, but homolysis of the NiII-P bond is still undisclosed. Herein, we describe the homolysis of NiII-P bonds via ligand to metal charge transfer to access active nickel(I) complexes and phosphorus-centered radicals under visible-light irradiation for C-P couplings of diaryl phosphine oxides with aryl bromides. Experimental studies demonstrated that visible light enabled homolysis of the NiII-P bond and the NiI/NiIII self-sustained cycle was involved in C-P bond formation. Furthermore, homolysis of the NiII-P bond can be applied to the hydrophosphination of [1.1.1]propellane in single-nickel photocatalysis.

Visible-Light-Activated Nickel Thiolates for C-S Couplings.

Thiolates are known as the inhibitors of metal catalysis due to their strong coordination with the metal. Herein, we reported visible-light-induced homolysis of the Ni-S bond to activate the nickel(II) thiolates for the C-S coupling, obviating the use of exogenous photocatalysts and other additives. Various aryl bromides/iodides can efficiently couple with thiols with a wide range of functional groups under mild conditions. Preliminary mechanistic studies suggested the homolysis of the Ni-S bond is the key step for couplings and nickel(0) is not involved in the process.

Silylacylation of Alkenes through N-Heterocyclic Carbene Catalysis.

The construction of silicon-containing molecules has received increasing attention in recent years. Herein, we report the generation of silyl radicals through NHC catalysis under mild reaction conditions. This methodology offers a novel and convenient route to a diverse range of ß-silyl ketones with a broad substrate scope and good functional group compatibility. Both the radical clock and electrochemical studies are consistent with the hypothesis of ground-state SET, and a plausible mechanism for the organocatalytic transformation is proposed.

Light-Promoted Arylsilylation of Alkenes with Hydrosilanes.

Herein, we report light-promoted photo/hydrogen atom transfer dual catalysis for arylsilylation of alkenes via the radical-radical cross-coupling with diverse hydrosilanes, which provides a simple and efficient method to prepare various organosilicon compounds with a wide range of substrate scope and good functional group tolerance under transition-metal- and chemical-oxidant-free conditions. Furthermore, the arylsilylation of alkenes can also proceed via the possible electron donor-acceptor complex under exogenous photocatalyst-free conditions.

Catalytic asymmetric ring-opening of meso-aziridines with malonates under heterodinuclear rare earth metal Schiff base catalysis.

Catalytic asymmetric ring-opening of meso-aziridines with malonates is described. The combined use of two rare earth metal sources with different properties promoted the desired ring-opening reaction. A 1:1:1 mixture of a heterobimetallic La(O-iPr)(3)/Yb(OTf)(3)/Schiff base 1a (0.25-10 mol %) efficiently promoted the reaction of five-, six-, and seven-membered ring cyclic meso-aziridines as well as acyclic meso-aziridines with dimethyl, diethyl, and dibenzyl malonates, giving chiral cyclic and acyclic γ-amino esters in 99-63% yield and >99.5-97% ee.

Rh-catalyzed aldehyde-aldehyde cross-aldol reaction under base-free conditions: in situ aldehyde-derived enolate formation through orthogonal activation.

The chemoselective generation of aldehyde-derived enolates to realize an aldehyde-aldehyde cross-aldol reaction is described. A combined Rh/dippf system efficiently promoted the isomerization/aldol sequence by using primary allylic, homoallylic, and bishomoallylic alcohols; secondary allylic and homoallylic alcohols; and trialkoxyboranes that were derived from primary allylic and homoallylic alcohols. The reaction proceeded at ambient temperature under base-free conditions, thus giving cross-aldol products with high chemoselectivity. Mechanistic studies, as well as its application to double-aldol processes under protecting-group-free conditions, are also described.