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A catalytic γ-selective syn -hydroarylation of alkenyl carbonyl compounds using arylboronic acids has been developed using a substrate directivity approach with a palladium(II) catalyst. This method tolerates a wide range of...
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This report presents a structure-guided approach for the optimization of VANOL-derived imidodiphosphorimidates as catalysts for the halonium-ion-induced spiroketalization reaction. Fine tuning of the catalyst active site, alongside enhanced acidity, were required to achieve high catalytic activity for the spiroketalization reaction. A wide range of...
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... Recently elegant developments have built up on the rapid emergence of metal-hydride chemistry 19,20,27 , and the directing group approach [31][32][33][34][35][36][37][38][39][40][41][42] . For instance, Zhu has developed a Ni-H initiated hydroarylation of 1,2-disubstituted alkenes with aryl iodides as the arylating reagents in the presence of stoichiometric silanes 30 . ...
... For instance, Zhu has developed a Ni-H initiated hydroarylation of 1,2-disubstituted alkenes with aryl iodides as the arylating reagents in the presence of stoichiometric silanes 30 . Engle 32,33,36,37 , Loh 34,38-40 , Chen 35 , and others 41,42 have demonstrated the hydroarylation of internal alkenes via a directing group approach which provides the precise control of the regioselectivity via cyclometallation. Despite the noteworthy advances, the development of a general method under redox-neutral conditions without extra reductants for the hydroarylation of undirected 1,2-substituted internal alkenes is still lacking and highly desired. ...
The transition metal-catalyzed hydrofunctionalization of alkenes offers an efficient solution for the rapid construction of complex functional molecules, and significant progress has been made during last decades. However, the hydrofunctionalization of internal alkenes remains a significant challenge due to low reactivity and the difficulties of controlling the regioselectivity. Here, we report the hydroarylation and hydroalkenylation of internal alkenes lacking a directing group with aryl and alkenyl boronic acids in the presence of a nickel catalyst, featuring a broad substrate scope and wide functional group tolerance under redox-neutral conditions. The key to achieving this reaction is the identification of a bulky 1-adamantyl β -diketone ligand, which is capable of overcoming the low reactivity of internal 1,2-disubstituted alkenes. Preliminary mechanistic studies unveiled that this reaction undergoes an Ar-Ni(II)-H initiated hydroarylation process, which is generated by the oxidative addition of alcoholic solvent with Ni(0) species and sequential transmetalation. In addition, the oxidative addition of the alcoholic solvent proves to be the turnover-limiting step.
... For instance, Zhu has developed a Ni-H initiated hydroarylation of 1,2-disubstituted alkenes with aryl iodides as the arylating reagents in the presence of stochiometric silanes 30 . Engle 32,33,36,37 , Loh 34,38-40 , Chen 35 , and others 41,42 have demonstrated the hydroarylation of internal alkenes via a directing group approach which provides the precise control of the regioselectivity via cyclometallation. Despite the noteworthy advances, the development of a general method under redox-neutral conditions without extra reductants for the hydroarylation of undirected 1,2-substituted internal alkenes is still lacking and highly desired. ...
The transition metal-catalyzed hydrofunctionalization of alkenes offers an efficient solution for the rapid construction of complex functional molecules, and significant progress has been made during last decades. However, the hydrofunctionalization of internal alkenes remains a significant challenge due to the low reactivity and the difficulties of controlling the regioselectivity. Here, we report the hydroarylation and hydroalkenylation of internal alkenes lacking a directing group with aryl and alkenyl boronic acids in the presence of a nickel catalyst, featuring a broad substrate scope and wide functional group tolerance under redox-neutral conditions. The key to achieving this reaction is the identification of a bulky 1-adamantyl β-diketone ligand, which is capable of overcoming the low reactivity of internal 1,2-disubstituted alkenes. Preliminary mechanistic studies unveiled that this reaction underwent an Ar-Ni(II)-H initiated hydroarylation process, which is generated by the oxidative addition of alcoholic solvent with Ni(0) species and sequential transmetalation. In addition, the oxidative addition of the alcoholic solvent proves to be the rate-determining step of this novel process.
... Recently, Engle and coworkers developed a palladiumcatalyzed redox-neutral method for γ-selective hydroarylation of β,γ-unsaturated carbonyl compounds with arylboronic acids for the first time. [8] They installed a Daugulis's 8-aminoquinoline (AQ) directing group [9] into 3-butenoic acid, and the AQ-masked substrate 1 a was efficiently hydroarylated with arylboronic acid 2 a, furnishing the desired product 3 a in good yields (see Scheme 1). The installation of the AQ directing group was the key to the success, and the authors proposed that the chelation of AQ enhanced the catalytic activity and forced an incoming nucleophile to attack on the C3-position in a regiospecific manner. ...
... On the basis of kinetic analyses, Engle and coworkers recognized the catalyst deactivation during the reaction, but the consequent product inhibition was not significant. [8] How were these side reactions leading to the catalyst deactivation effectively suppressed? The following discussion will answer this question. ...
... It should be mentioned that a small amount of C2deuterated products were detected when using D 2 O or PhB (OD) 2 as the source of deuterons in control experiments, [8] indicating that both H 2 O and BF(OH) 2 could be a competent proton donor in addition to acetic acid. However, the located transition state of the protodepalladation step with either H 2 O or BF(OH) 2 as proton donor is quite high-lying in terms of freeenergy barriers (see Figure S1 in the Supporting Information). ...
Density functional calculations were carried out on the mechanism of a palladium‐catalyzed hydroarylation reaction of β,γ‐unsaturated carbonyl compounds with arylboronic acids reported by Engle's group. The proposed reaction pathway consists of several key mechanistic steps, including the chelation of substrate 1 a, transmetalation of organoboron 2 a, migratory insertion, protodepalladation, and dechelation of product 3 a, among which the transmetalation step is rate‐determining with a free‐energy barrier of 27.0 kcal/mol. Experimental researchers proposed that the chelation of Daugulis's 8‐aminoquinoline (AQ) directing group facilitated the desired hydroarylation in a γ‐selective manner. However, the present study revealed that the chelation of AQ indeed retarded the delivery of the aryl group to the double bond and the regioselectivity was not necessarily the result of this group. Indeed, it could effectively prevent the homocoupling of 2 a, because the homocoupling was predicted to be easier than the desired hydroarylation in the absence of AQ. Additionally, some reductive coupling pathways between 1 a and 2 a were designed, and the competition of them was discussed in great detail. Lastly, the extension of this synthetic strategy to other types of alkenes was predicted.
... During the past 5 years, our laboratories have developed a variety of transition-metal-catalyzed, three-component directed alkene 1,2-difunctionalization reactions facilitated by the 8aminoquinoline (AQ) auxiliary, a strongly coordinating bidentate directing group. Using this strategy we and others have reported examples of hydrofunctionalization [21][22][23][24][25][26][27][28][29][30][31][32][33] , dicarbofunctionalization [34][35][36][37][38][39] , carboamination 40,41 , and carbo-/aminoboration [42][43][44][45] , among other transformations 46,47 (Fig. 1c). We recognized several issues that would need to be addressed to bring a directed (hetero)annulation process to fruition: (1) phenols and anilines have previously proven to be ineffective coupling partners in AQ-directed alkene additions in our hands, leading to the hypothesis that nucleopalladation in these cases is endergonic; (2) due to their intramolecular nature, the oxidative addition and reductive elimination transitions states involving Pd(IV) would likely be highly strained; and (3) competitive pathways arising from Heck-type or Wacker-type oxidative alkene addition or hydrofunctionalization could predominate. ...
2,3-Dihydrobenzofurans and indolines are common substructures in medicines and natural products. Herein, we describe a method that enables direct access to these core structures from non-conjugated alkenyl amides and ortho-iodoanilines/phenols. Under palladium(II) catalysis this [3 + 2] heteroannulation proceeds in an anti-selective fashion and tolerates a wide variety of functional groups. N-Acetyl, -tosyl, and -alkyl substituted ortho-iodoanilines, as well as free –NH2 variants, are all effective. Preliminary results with carbon-based coupling partners also demonstrate the viability of forming indane core structures using this approach. Experimental and computational studies on reactions with phenols support a mechanism involving turnover-limiting, endergonic directed oxypalladation, followed by intramolecular oxidative addition and reductive elimination.
... Stilbenoid as important aryl olefins are widely used in important fields such as materials, medical drugs, hygiene, and cosmetics. Diarylethene [1] and its derivatives, as the parent structures of stilbenoid, are structural units for the synthesis of fluorescent materials [2,3], flavors [4], biologically active [5] and natural product intermediates [6,7], especially in fluorescent materials and natural products such as piceatannol-mic-4 (anti-inflammatory, antibacterial) [8], piceatannol-mic-5 (anti -biological activity) [9] and DBF (anti-tumor, hypolipidemic) [10]. In addition, Schiff base 2-cyano stilbene [11] and the compound BBU [12] are used in the field of fluorescent materials. ...
A bis-quinoline-2-carboxylic acid copper salt as a single crystal was prepared and characterized by X-ray single crystal analysis. The crystal as a catalyst was applied to the Mizoroki–Heck coupling reaction between arylboronic acids and α-olefins. A series of diarylethenes and aryl olefins were synthesized with good to excellent yields at room temperature. The catalytic system exhibited good functional group tolerance and low pollution.
Graphic Abstract
A bis-quinoline-2-carboxylic acid copper salt as a single crystal was prepared and characterized by X-ray single crystal analysis. The crystal as a catalyst was applied to the Mizoroki–Heck coupling reaction between arylboronic acids and α-olefins Open image in new window .
... The synthesis of nocardiolactone was also described in this paper. The palladium-catalyzed γ-selective hydroarylation of a β,γ-unsaturated secondary amide was reported by Engle (Table 11, entry 3) [192]. In his report, palladium acetate was used to catalyze a regioselective hydroarylation with arylboronic acids, although the substrate scope was limited to amides bearing the N-8-aminoquinoline (AQ) substituent. ...
... amide was reported by Engle (Table 11, entry 3) [192]. In his report, palladium acetate was used to catalyze a regioselective hydroarylation with arylboronic acids, although the substrate scope was limited to amides bearing the N-8-aminoquinoline (AQ) substituent. ...
Indole derivatives are associated with a variety of both biological activities and applications in the field of material chemistry. A number of different strategies for synthesizing substituted indoles by means of the reactions of indolylboronic acids with electrophilic compounds are considered the methods of choice for modifying indoles because indolylboronic acids are easily available, stable, non-toxic and new reactions using indolylboronic acids have been described in the literature. Thus, the aim of this review is to summarize the methods available for the preparation of indolylboronic acids as well as their chemical transformations. The review covers the period 2010–2019.
The reductive Heck hydroarylation of unactivated alkenes has emerged as an essential reaction for regioselective hydroarylation. Herein, we report a palladium-catalyzed reductive Heck hydroarylation of unactivated alkenes under mild conditions with enhanced functional group tolerance using hydrosilane as the reducing reagent. Under the optimal conditions, the alkylarene yields increased, resulting in minimal undesired products. Mechanistic studies using deuterated reagents indicated the involvement of two competing catalytic cycles.
The precise control of the regioselectivity in the transition metal‐catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickelcatalyzed migratory β‐selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)‐H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)‐H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2‐aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.
The precise control of the regioselectivity in the transition metal‐catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel‐catalyzed migratory β‐selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)‐H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)‐H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2‐aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.
