Palladium‐Catalyzed Asymmetric Reductive Heck Reaction of Aryl Halides

Yue, Guizhou; Lei, Kaining; Hirao, Hajime; Zhou, Jianrong

doi:10.1002/anie.201501712

Cited by 153 publications

(74 citation statements)

References 104 publications

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“…This compound was synthesized using the literature modified procedure: [20] the methoxylamine hydrochloride (3.0 equiv.) was added to a solution of 2 a (0.25 mmol) in MeOH (1 mL) with stirring.…”

Section: Typical Procedures For Synthesis Of 3-phenyl-23-dihydro-1h-imentioning

confidence: 99%

Palladium Nanoparticles‐Catalyzed Synthesis of Indanone Derivatives via Intramolecular Reductive Heck Reaction

Parveen

Sekar

2019

Adv Synth Catal

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An efficient protocol for the straightforward, single-step synthesis of 3-aryl-1-indanones from 2'iodochalcone via reductive Heck reaction using phosphine free, stable and reusable binaphthyl stabilized palladium nanoparticle (Pd-BNP) as a catalyst has been described. An immense array of substrate scope with electron-rich and deficient 2'-iodochalcones have been synthesized. Further derivatization of product indanones have been achieved successfully. The heterogeneous nature of the Pd-BNP has been validated by centrifugation test and mercury poisoning experiment. Pd-BNP has been successfully recycled up to 5 cycles without any significant loss in reaction yield and particle size of nanoparticles, confirmed by TEM analysis. 3-(4-(Trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-one(2 r): 78% yield (53.8 mg); Yellow liquid; R f 0.53 (10% ethyl acetate in hexanes); 1 H NMR (400 MHz, CDCl 3 ): δ 2.66 (dd, cm À 1 ; HRMS (m/z): [M + Na] + calcd for C 16 H 11 OF 3 Na: 299.0660; found: 299.0651. 3-(3-Nitrophenyl)-2,3-dihydro-1H-inden-1-one (2 s): 70% yield (44.3 mg); Greenish solid; mp 125°C; R f 0.42 (20% ethyl acetate in hexanes); 1 H NMR (400 MHz, CDCl 3 ): δ 2.66 (dd,

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Section: Typical Procedures For Synthesis Of 3-phenyl-23-dihydro-1h-imentioning

confidence: 99%

Palladium Nanoparticles‐Catalyzed Synthesis of Indanone Derivatives via Intramolecular Reductive Heck Reaction

Parveen

Sekar

2019

Adv Synth Catal

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“…who used aryl triflates in an intramolecular fashion to synthesize chiral 3‐substituted indanones with moderate enantiomeric excess ( ee ) values in most cases . More recently, an enantioselective palladium‐phosphine‐catalyzed intramolecular reductive Heck reaction of aryl halides was reported to afford 3‐arylindanones with moderate to high ee values . It was proposed that the addition of trialkylammonium salts in ethylene glycol facilitates the halide dissociation through its hydrogen bond donor capacity.…”

Section: Introductionmentioning

confidence: 99%

“…Another enantioselective transformation of this class was reported with the asymmetric arylative dearomatization of indoles through palladium‐phosphine‐catalyzed reductive Heck reaction using sodium formate in methanol . To date, the asymmetric reductive Heck reaction is rather limited to intramolecular reactions, which is particularly interesting for the synthesis of natural products . To the best of our knowledge, there are no examples that describe the “direct intermolecular” enantioselective reductive Heck reaction with a high ee , most likely because of the challenges involved in the asymmetric induction step.…”

Section: Introductionmentioning

confidence: 99%

Importance of the Reducing Agent in Direct Reductive Heck Reactions

et al. 2017

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The role of the reductant in the palladium N‐heterocyclic carbene (NHC) catalyzed reductive Heck reaction and its effect on the mechanism of the reaction is reported. For the first time in this type of transformation, the palladium‐NHC‐catalyzed reductive Heck reaction was shown to proceed in the presence of LiOMe and iPrOH even at 10 °C to give the products very efficiently in excellent yields and with exceptional chemoselectivities. This study shows that the reaction proceeds through two distinct mechanisms that depend on the nature of the reducing agent. In the presence of a protic solvent or acidic medium the reaction undergoes protonation to yield the reduced product, whereas in the absence of proton source, it proceeds through the insertion of the reductant followed by reductive elimination. The kinetic data reveal that the oxidative addition is the rate‐determining step in the reaction. The reaction profiles show first‐order kinetics in aryl iodide and Pd and zero‐order kinetics in LiOMe, benzylideneacetone, and the excess amount of NHC ligand. In addition, the reaction progress kinetic analysis shows that neither catalyst decomposition nor product inhibition occurs during the reaction. DFT calculations of the key steps confirm that the oxidative addition step is the rate‐determining step in the reaction. Deuterium‐labeling experiments indicate that the product is formed by the protonation of the Pd−Calkyl bond of the intermediate formed after enone insertion into the Pd−CAr bond. Application of chiral NHC ligands in the asymmetric reductive Heck reaction only results in poor enantioselectivities (enantiomeric excess up to 20 %) and is also substrate specific. DFT calculations suggest that the migration of the aryl group to the alkene of the substrate is the enantioselectivity‐determining step of the reaction. It is further shown that if the steric bulk at the enone is small (a methyl group), the two transition state barriers from [PdII(L2)(ArI)(enone)] species Cre and Csi, which have the re and si face of the enone substrate coordinated to Pd, are very similar, in line with the experimental results. With a slightly larger group (an isopropyl substituent) a significant difference in energy barriers is calculated (2.6 kcal mol−1), and in the experiment this product is formed with a modest enantiomeric excess (up to 20 %).

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“…Heck arylations with these ligands provided the Heck product 3a in good yields (82-83 %), high regiocontrol (> 20:1), and excellent enantiomeric ratios of 98:2, and 97:3, respectively (Scheme 2). Further optimization enabled us to decrease the loading of both Pd(TFA) 2 and L5 or L6 to only 2mol %, the lowest reported catalyst loading for an intermolecular enantioselective Heck reaction with acyclic olefins,without losses in chemical yields or stereoselectivity.…”

mentioning

confidence: 99%

Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)‐Verapamil

2015

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We describe herein a highly regio- and enantioselective Pd-catalyzed Heck arylation of unactivated trisubstituted acyclic olefins to provide all-carbon quaternary stereogenic centers. Chiral N,N ligands of the pyrimidine- and pyrazino-oxazoline class were developed for that purpose, providing the desired products in good to high yields with enantiomeric ratios up to >99:1. Both linear and branched substituents on the olefins were well-tolerated. The potential of this new method is demonstrated by the straightforward synthesis of several O-methyl lactols and lactones containing quaternary stereocenters, together with a concise enantioselective total synthesis of the calcium channel blocker verapamil.

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Palladium‐Catalyzed Asymmetric Reductive Heck Reaction of Aryl Halides

Abstract: Asymmetric reductive Heck reaction of aryl halides is realized in high stereoselectivity. Hydrogen-bond donors, trialkylammonium salts in a glycol solvent, were used to promote halide dissociation from neutral arylpalladium complexes to access cationic, stereoselective pathways.

Cited by 153 publications

References 104 publications

Palladium Nanoparticles‐Catalyzed Synthesis of Indanone Derivatives via Intramolecular Reductive Heck Reaction

Palladium Nanoparticles‐Catalyzed Synthesis of Indanone Derivatives via Intramolecular Reductive Heck Reaction

Importance of the Reducing Agent in Direct Reductive Heck Reactions

Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)‐Verapamil

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