51052-00-7Relevant articles and documents
Markovnikov Wacker-Tsuji Oxidation of Allyl(hetero)arenes and Application in a One-Pot Photo-Metal-Biocatalytic Approach to Enantioenriched Amines and Alcohols
Albarrán-Velo, Jesús,Gotor-Fernández, Vicente,Lavandera, Iván
, p. 4096 - 4108 (2021/08/19)
The Wacker-Tsuji aerobic oxidation of various allyl(hetero)arenes under photocatalytic conditions to form the corresponding methyl ketones is presented. By using a palladium complex [PdCl2(MeCN)2] and the photosensitizer [Acr-Mes]ClO4 in aqueous medium and at room temperature, and by simple irradiation with blue led light, the desired carbonyl compounds were synthesized with high conversions (>80%) and excellent selectivities (>90%). The key process was the transient formation of Pd nanoparticles that can activate oxygen, thus recycling the Pd(II) species necessary in the Wacker oxidative reaction. While light irradiation was strictly mandatory, the addition of the photocatalyst improved the reaction selectivity, due to the formation of the starting allyl(hetero)arene from some of the obtained by-products, thus entering back in the Wacker-Tsuji catalytic cycle. Once optimized, the oxidation reaction was combined in a one-pot two-step sequential protocol with an enzymatic transformation. Depending on the biocatalyst employed, i. e. an amine transaminase or an alcohol dehydrogenase, the corresponding (R)- and (S)-1-arylpropan-2-amines or 1-arylpropan-2-ols, respectively, could be synthesized in most cases with high yields (>70%) and in enantiopure form. Finally, an application of this photo-metal-biocatalytic strategy has been demonstrated in order to get access in a straightforward manner to selegiline, an anti-Parkinson drug. (Figure presented.).
An Efficient Palladium-Catalyzed α-Arylation of Acetone below its Boiling Point
Ledgard, Andrew J.,Martin, Fionna M.,Mutton, Simon P.,Richardson, Jeffery,Walton, Lesley
, (2020/07/24)
The monoarylation of acetone is a powerful transformation, but is typically performed at temperatures significantly in excess of its boiling point. Conditions described for performing the reaction at ambient temperatures led to significant dehalogenation when applied to a complex aryl halide. We describe our attempts to overcome both issues in the context of our drug-discovery program.
Nickel-Catalyzed Mono-Selective α-Arylation of Acetone with Aryl Chlorides and Phenol Derivatives
Amgoune, Abderrahmane,Derhamine, Sary Abou,Krachko, Tetiana,Monteiro, Nuno,Pilet, Guillaume,Schranck, Johannes,Tlili, Anis
supporting information, p. 18948 - 18953 (2020/09/01)
The challenging nickel-catalyzed mono-α-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-α-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives. The methodology has been extended to the unprecedented coupling of acetone with phenol derivatives. Mechanistic studies allowed the isolation and characterization of key Ni0 and NiII catalytic intermediates. The Josiphos ligand is shown to play a key role in the stabilization of NiII intermediates to allow a Ni0/NiII catalytic pathway. Mechanistic understanding was then leveraged to improve the protocol using an air-stable NiII pre-catalyst.
Iron powder and tin/tin chloride as new reducing agents of Meerwein arylation reaction with unexpected recycling to anilines
Abdelwahab, Ahmed B.,El-Sawy, Eslam R.,Kirsch, Gilbert
supporting information, p. 526 - 538 (2020/01/08)
Simple and rapid route for Meerwein arylation reaction using iron powder or a mixture of tin/tin chloride has been developed. In the presence of iron powder, different aryl diazonium salts reacted with methyl vinyl ketone, acrylates, and isopropenyl acetate. Production of oximes was detected as the main product with acrylates or in a mixture with β-aryl methyl ketones in the case of methyl vinyl ketone. The in situ produced HNO2 from an excess of NaNO2/HCl was trapped by alkyl aryl radical to form oximes in the E configuration form. The presence of tin/tin chloride mixture in the reaction of the aryl diazonium salts with methyl vinyl ketone produced Michael products along with β-aryl methyl ketones. The predicted α-aryl methyl ketones from the reaction of isopropenyl acetate with the diazotized anilines were obtained using iron or tin/tin chloride mixture.
Metal Cocatalyst Directing Photocatalytic Acetonylation of Toluene via Dehydrogenative Cross-Coupling with Acetone
Tyagi, Akanksha,Matsumoto, Tomoya,Yamamoto, Akira,Kato, Tatsuhisa,Yoshida, Hisao
, p. 31 - 38 (2019/08/20)
Abstract: A heterogeneous metal-loaded titanium oxide photocatalyst provided an efficient route to bring out direct dehydrogenative cross-coupling between toluene and acetone without consuming any additional oxidizing agent. The nature of the metal nanoparticle cocatalyst deposited on TiO2 photocatalyst dictated the product selectivity for the cross-coupling. Pd nanoparticles on TiO2 photocatalyst allowed a C–C bond formation between the aromatic ring of toluene and acetone to give 1-(o-tolyl)propan-2-one (1a1) with high regioselectivity, while Pt nanoparticles on TiO2 photocatalyst promoted the cross-coupling between the methyl group of toluene and acetone to give 4-phenylbutan-2-one (1b) as the acetonylated product. These results demonstrated that the selection of the metal cocatalyst on TiO2 photocatalyst could determine which C–H bonds in toluene, aromatic or aliphatic, can react with acetone. Two kinds of reaction mechanisms were proposed for the photocatalytic dehydrogenative cross-coupling reaction, depending on the property of the metal nanoparticles, i.e., only Pd nanoparticles can catalyze the reaction between aromatic ring and the acetonyl radical species. Graphic Abstract: [Figure not available: see fulltext.].
Stereoselective Synthesis of 1-Arylpropan-2-amines from Allylbenzenes through a Wacker-Tsuji Oxidation-Biotransamination Sequential Process
González-Martínez, Daniel,Gotor, Vicente,Gotor-Fernández, Vicente
, p. 2582 - 2593 (2019/05/15)
Herein, a sequential and selective chemoenzymatic approach is described involving the metal-catalysed Wacker-Tsuji oxidation of allylbenzenes followed by the amine transaminase-catalysed biotransamination of the resulting 1-arylpropan-2-ones. Thus, a series of nine optically active 1-arylpropan-2-amines were obtained with good to very high conversions (74–92%) and excellent selectivities (>99% enantiomeric excess) in aqueous medium. The Wacker-Tsuji reaction has been exhaustively optimised searching for compatible conditions with the biotransamination experiments, using palladium(II) complexes as catalysts and iron(III) salts as terminal oxidants in aqueous media. The compatibility of palladium/iron systems for the chemical oxidation with commercially available and made in house amine transaminases was analysed, finding ideal conditions for the development of a general and stereoselective cascade sequence. Depending on the selectivity displayed by selected amine transaminase, it was possible to produce both 1-arylpropan-2-amines enantiomers under mild reaction conditions, compounds that present therapeutic properties or can be employed as synthetic intermediates of chiral drugs from the amphetamine family. (Figure presented.).
Enantioselective Bromolactonization of Trisubstituted Olefinic Acids Catalyzed by Chiral Pyridyl Phosphoramides
Nishikawa, Yasuhiro,Hamamoto, Yuhta,Satoh, Rika,Akada, Naho,Kajita, Shuhei,Nomoto, Marina,Miyata, Megumi,Nakamura, Madoka,Matsubara, Chinatsu,Hara, Osamu
supporting information, p. 18880 - 18885 (2018/12/04)
Enantioselective bromolactonization of trisubstituted olefinic acids producing synthetically useful chiral lactones with two contiguous asymmetric centers has remained mainly unexplored except for the 6-exo cyclization mode. In this work, the 5-exo- and 6
Transition-Metal-Free Homologative Cross-Coupling of Aldehydes and Ketones with Geminal Bis(boron) Compounds
Stephens, Thomas C.,Pattison, Graham
supporting information, p. 3498 - 3501 (2017/07/15)
We report a transition-metal-free coupling of aldehydes and ketones with geminal bis(boron) building blocks which provides the coupled, homologated carbonyl compound upon oxidation. This reaction not only extends an alkyl chain containing a carbonyl group, it also simultaneously introduces a new carbonyl substituent. We demonstrate that enantiopure aldehydes with an enolizable stereogenic center undergo this reaction with complete retention of stereochemistry.
Process for Making CGRP Receptor Antagonists
-
, (2016/06/01)
The invention encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, which are CGRP receptor antagonists useful for the treatment of migraine.
Design of an Indolylphosphine Ligand for Reductive Elimination-Demanding Monoarylation of Acetone Using Aryl Chlorides
Fu, Wai Chung,So, Chau Ming,Chow, Wing Kin,Yuen, On Ying,Kwong, Fuk Yee
supporting information, p. 4612 - 4615 (2015/09/28)
The rational design of a phosphine ligand for the reductive elimination-demanding Pd-catalyzed mono-α-arylation of acetone is demonstrated and reported. The catalyst is tolerant of previously proven challenging electron-deficient aryl chlorides and provides excellent product yields with down to 0.1 mol % Pd. Preliminary investigations suggest that the rate-limiting step for the proposed system is the oxidative addition of aryl chlorides, in which it contradicts previous findings regarding the α-arylation of acetone with aryl halides.
