Metal-Controlled Enantiodivergent Tandem Rearrangement to Synthesize 2H-Azirines.

A metal-controlled enantiodivergent rearrangement of α-diazo-β-keto oxime ethers has been developed. Switching the metal catalyst from Co(II) to Fe(II) with an identical ligand completely reverses the asymmetric induction. Both enantiomers of chiral 2H-azirines and its derivatives are accessible under thermal or photolytic conditions.

Catalytic Asymmetric Rearrangement of Azoalkene-Derived Sulfonium Ylides via Remote Chirality Control.

The [2,3]-sigmatropic rearrangement has been widely utilized to construct C-S bonds. Herein, we report an enantioselective, intermolecular, and noncarbenoid [2,3]-sigmatropic rearrangement of sulfonium ylides using azoalkenes. This process features a broad substrate scope, high efficiency, and excellent enantioselectivity, achieving yields of up to 99% and an enantiomeric excess (ee) of up to 96%.

Anti-Markovnikov hydroallylation reaction of alkenes via scandium-catalyzed allylic C‒H activation.

Compared with rare-earth (RE)…heteroatom interaction, RE…π interaction, frequently used in facilitating regio- and stereoselectivity of olefin polymerizations, is seldomly used to trigger catalytic C - H functionalization. Here, we describe a direct anti-Markovnikov hydroallylation reaction of styrene derivatives with 1-aryl-2-alkyl alkenes and α-alkenes by use of RE…π interaction. This protocol provides a straightforward and atom-efficient route for the synthesis of valuable chain elongated internal alkenes (65 examples, up to 99% yield, > 19:1 E/Z ratio).

Post-Transition-State Dynamic Effects in the Transmetalation of Pd(II)-F to Pd(II)-CF.

The observation of post-transition-state dynamic effects in the context of metal-based transformation is rare. To date, there has been no reported case of a dynamic effect for the widely employed class of palladium-mediated coupling reactions. We performed an experimental and computational study of the trifluoromethylation of PdF, which is a key step in the Pd/Pd-catalyzed trifluoromethylation of aryl halides or acid fluorides.

Iron-Catalyzed Asymmetric α-Alkylation of 2-Acylimidazoles via Dehydrogenative Radical Cross-Coupling with Alkanes.

The direct α-alkylation of acyclic carbonyls with nonactivated hydrocarbons through C(sp )-H functionalization is both extremely promising and notably challenging, especially when attempting to achieve enantioselectivity using iron-based catalysts. We have identified a robust chiral iron complex for the oxidative cross-coupling of 2-acylimidazoles with benzylic and allylic hydrocarbons, as well as nonactivated alkanes. The readily available and tunable N,N'-dioxide catalysts of iron in connection with oxidants exhibit precise asymmetric induction (up to 99 % ee) with good compatibility in moderate to good yields (up to 88 % yield).

Catalytic Enantioselective Nucleophilic Addition to Arynes by a New Quaternary Guanidinium Salt-Based Phase-Transfer Catalyst.

Owing to the mild generation methods, arynes have been widely used in synthetic chemistry. However, achieving asymmetric organocatalytic reactions with arynes remains a formidable and infrequent challenge, primarily because these neutral and transient species tend to spontaneously quench. To address this issue, a solid-liquid phase-transfer strategy is devised in which the generation speed of arynes could be controlled by the generated fluoride-based chiral phase-transfer catalyst.

Chiral ,'-Dioxide Ligands Tune Diastereoselectivity in Mg(II)-Catalyzed Asymmetric Ring-Opening Desymmetrization of Azetidiniums.

A diastereodivergent asymmetric desymmetrization of azetidinium salts with benzothiazoleamides as carbon nucleophiles through a chiral ,'-dioxide/Mg(II) complex-promoted ring-opening reaction is realized by tuning ligands. Both - and -chiral δ-amino acid derivatives bearing benzothiazole structure were obtained in moderate to good yields and dr and ee values. DFT calculations indicated that the diastereodivergency stems from the different size of the chiral pocket formed by variable substructures of the ligands, leading to the opposite attack direction of the nucleophiles.

.

Asymmetric epoxidation of alkenes catalyzed by nonheme chiral Mn-O and Fe-O catalysts has been well established, but chiral Co-O catalysts for the purpose remain virtually undeveloped due to the oxo wall. Herein is first reported a chiral cobalt complex to realize the enantioselective epoxidation of cyclic and acyclic trisubstituted alkenes by using PhIO as the oxidant in acetone, wherein the tetra-oxygen-based chiral ,'-dioxide with sterically hindered amide subunits plays a crucial role in supporting the formation of the Co-O intermediate and enantioselective electrophilic oxygen transfer. Mechanistic studies, including HRMS measurements, UV-vis absorption spectroscopy, magnetic susceptibility, as well as DFT calculations, were carried out, confirming the formation of Co-O species as a quartet Co(III)-oxyl tautomer.

Direct Amination of α-Triaryl Alcohols via Vanadium Catalysis.

α-Triaryl amines have been used as pharmaceuticals and pharmaceutical intermediates for antifungal and anticancer applications. Current methods to synthesize such compounds require at least two steps, and no direct amination of tertiary alcohols has been reported. Herein, we disclose efficient catalytic conditions for the direct amination of α-triaryl alcohols to access α-triaryl amines.

Nickel-Catalyzed Enantioselective Reductive Arylation and Heteroarylation of Aldimines via an Elementary 1,4-Addition.

Nickel catalysts of chiral pyrox ligands promoted enantioselective reductive arylation and heteroarylation of aldimines, using directly (hetero)aryl halides and sulfonates. The catalytic arylation can also be conducted with crude aldimines generated from condensation of aldehydes and azaaryl amines. Mechanistically, density functional theory (DFT) calculations and experiments pointed to an elementary step of 1,4-addition of aryl nickel(I) complexes to -azaaryl aldimines.

Nickel-Catalyzed Enantioselective Reductive Conjugate Arylation and Heteroarylation via an Elementary Mechanism of 1,4-Addition.

A nickel complex of isoquinox promoted enantioselective conjugate arylation and heteroarylation of enones using aryl and heteroaryl halides directly. The reaction was successfully applied to stereoselective syntheses of -turmerone, chiral fragments of (+)-tolterodine and AZD5672. Mechanistically, experiments and calculations supported that an arylnickel(I) complex inserted to enones via an elementary 1,4-addition.

Rh-Catalyzed [4 + 2] Annulation with a Removable Monodentate Structure toward Iminopyranes and Pyranones by C-H Annulation.

The Rh-catalyzed reactions of -pyridinyl enaminones with internal alkynes leading to the synthesis of iminopyranes via a key C-H bond activation and subsequent tautomeric O-H bond cleavage are reported. Moreover, the pyridine ring in the amino group acts as an auxiliary monodentate site for this annulation and can be easily removed by a simple hydrolysis to afford pyranones.

Asymmetric Catalytic (2+1) Cycloaddition of Thioketones to Synthesize Tetrasubstituted Thiiranes.

Herein, we report the first example of enantioselective (2+1) cycloaddition of thioketones with α-diazo pyrazoleamides for the direct synthesis of tetrasubstituted thiiranes. In the presence of chiral N,N'-dioxide/cobalt(ΙΙ) complexes (2-5 mol%), excellent efficiency (up to 99 % yield within 15 mins) and high stereoselectivity (up to >19 : 1 dr and 97 % ee) are available. Elaborations of thiiranes via desulfuration have also been conducted to deliver tetrasubstituted olefins.

Enantioselective Synthesis of Nitriles Containing a Quaternary Carbon Center by Michael Reactions of Silyl Ketene Imines with 1-Acrylpyrazoles.

The enantioselective construction of quaternary carbon centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral -dioxide-Co(II) complex.

Asymmetric Domino Heck Arylation and Alkylation of Nonconjugated Dienes: Double C-F···Sodium Attractive Noncovalent Interaction.

Palladium catalyzes a domino Heck arylation and alkylation of nonconjugated cyclodienes to produce trans isomers of disubstituted cyclohexenes in exceptionally high enantiomeric ratios, reaching 100:1 to 200:1 in many cases. Importantly, the interactions of the two CF bonds of Josiphos and the sodium ion of malonates facilitates stereoselective allylic attack through DFT calculations and experiments. This is a new type of attractive noncovalent interactions found in organometallic catalysis.

Iron-Catalyzed Enantioselective Radical Carboazidation and Diazidation of α,β-Unsaturated Carbonyl Compounds.

Azidation of alkenes is an efficient protocol to synthesize organic azides which are important structural motifs in organic synthesis. Enantioselective radical azidation, as a useful strategy to install a C-N bond, remains challenging due to the inherently instability and unique structure of radicals. Here, we disclose an efficient enantioselective radical carboazidation and diazidation of -unsaturated ketones and amides catalyzed by chiral ,'-dioxide/Fe(OTf) complexes.

Enantioselective Formal Vinylogous N-H Insertion of Secondary Aliphatic Amines Catalyzed by a High-Spin Cobalt(II) Complex.

Vinylcarbene insertion into the nitrogen-hydrogen (N-H) bond of amines allows direct access to α,β-unsaturated γ-amino acid derivatives, meeting a marked challenge in the control of regio- and enantioselectivities. Here, we report a highly γ-selective and enantioselective insertion into N-H bonds of aliphatic or aromatic secondary amines with vinyl substituted α-diazo pyrazoleamides using a high-spin chiral -dioxide/cobalt(II) complex catalyst. The method affords a wide variety of valuable optically active - and -type vinyl γ-amino amides.

Catalytic Asymmetric Homologation of Ketones with α-Alkyl α-Diazo Esters.

The homologation of ketones with diazo compounds is a useful strategy to synthesize one-carbon chain-extended acyclic ketones or ring-expanded cyclic ketones. However, the asymmetric homologation of acyclic ketones with α-diazo esters remains a challenge due to the lower reactivity and complicated selectivity. Herein, we report the enantioselective catalytic homologation of acetophenone and related derivatives with α-alkyl α-diazo esters utilizing a chiral scandium(III) ,'-dioxide as the Lewis acid catalyst.

Enantioselective Intermolecular Heck and Reductive Heck Reactions of Aryl Triflates, Mesylates, and Tosylates Catalyzed by Nickel.

Nickel-catalyzed intermolecular Heck reaction of cycloalkenes proceeds well with aryl triflates, mesylates and tosylates in excellent enantiomeric ratios. The asymmetric reductive Heck reaction also works with a 2-cyclopentenone ketal, which is equivalent to conjugate arylation of the enone itself.

Computational Study on the Fate of Oxidative Directing Groups in Ru(II), Rh(III), and Pd(II) Catalyzed C-H Functionalization.

Activation of C-H bonds assisted by a directing group is indispensable in organic synthesis. Among them, utilizing oxidative directing groups that can serve as an internal oxidant to drive the M/M catalytic cycle has recently become a promising strategy. A survey of published reactions involving -alkoxyamides or -acyloxyamides reveals that not all N-O bonds act as an internal oxidant.

Asymmetric Reductive and Alkynylative Heck Bicyclization of Enynes to Access Conformationally Restricted Aza[3.1.0]bicycles.

Conformationally restricted azabicycles are becoming increasingly important in medicinal research. Asymmetric Heck bicyclization of enynes proceeds to give medicinally useful aza[3.1.