Atropisomeric Anilides Research Articles

Inherently Chiral 6,7-Diphenyldibenzo[ e,g ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Inherently Chiral 6,7-Diphenyldibenzo[ <i>e,g</i> ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Dynamic Kinetic Resolution of Atropisomeric Anilides via Palladium-Catalyzed C–H Olefination

Key words palladium catalysis - dynamic kinetic resolution - enantioselectivity - C–H activation

Enantioselective Synthesis of Atropisomeric Anilides via Pd(II)-Catalyzed Asymmetric C-H Olefination.

Atropisomeric anilides have received tremendous attention as a novel class of chiral compounds possessing restricted rotation around an N-aryl chiral axis. However, in sharp contrast to the well-studied synthesis of biaryl atropisomers, the catalytic asymmetric synthesis of chiral anilides remains a daunting challenge, largely due to the higher degree of rotational freedom compared to their biaryl counterparts. Here we describe a highly efficient catalytic asymmetric synthesis of atropisomeric anilides via Pd(II)-catalyzed atroposelective C-H olefination using readily available L-pyroglutamic acid as a chiral ligand. A broad range of atropisomeric anilides were prepared in high yields (up to 99% yield) and excellent stereoinduction (up to >99% ee) under mild conditions. Experimental studies indicated that the atropostability of those anilide atropisomers toward racemization relies on both steric and electronic effects. Experimental and computational studies were conducted to elucidate the reaction mechanism and rate-determining step. DFT calculations revealed that the amino acid ligand distortion is responsible for the enantioselectivity in the C-H bond activation step. The potent applications of the anilide atropisomers as a new type of chiral ligand in Rh(III)-catalyzed asymmetric conjugate addition and Lewis base catalysts in enantioselective allylation of aldehydes have been demonstrated. This strategy could provide a straightforward route to access atropisomeric anilides, one of the most challenging types of axially chiral compounds.

Enantioselective Atropisomeric Anilides Synthesis via Cu-Catalyzed Intramolecular Adjacent C–N Coupling

Catalytically asymmetric synthesis of atropisomeric compounds is an important research area in organic synthesis. However, in comparison with C–C atropisomers, the atropisomers caused by the restricted rotation of C–N single bonds have been given less attention because of the limited methods for accessing these compounds. Herein we report a Cu-catalyzed enantioselective intramolecular Ullmann-type amination reaction for the synthesis of C–N atropisomers. The C–N axial chirality was induced highly efficiently by the intramolecular adjacent C–N cross-coupling. The readily prepared N,N′-(cyclohexane-1,2-diyl)dipicolinamides showed high efficacy and stereoinduction (up to 99% ee).

ChemInform Abstract: Catalytic Enantioselective Synthesis of Novel Atropisomeric Compounds Having an N—C Chiral Axis and Their Application to Asymmetric Reaction

AbstractReview: ca. 50 refs.

炭素‐窒素不斉軸を有する新規アトロプ異性化合物の触媒的不斉合成と不斉反応への応用

Atropisomeric compounds due to rotational restriction around an N-C bond have received much attention recently as novel chiral molecules. However, catalytic enantioselective synthesis of such N-C axially chiral compounds has not so far been reported. We succeeded in the highly enantioselective syntheses of atropisomeric ortho-tert-butyl anilides, lactams and indoles having an N-C chiral axis through chiral palladium-catalyzed N-C bond forming reactions.That is, in the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation (Buchwald-Hartwig amination) of achiral ortho-tert-butylanilides with p-iodonitrobenzene proceeded in a highly enantioselective manner (88−96% ee) to give atropisomeric N-(p-nitrophenyl)anilides in good yields. The application of the present catalytic enantioselective N-arylation to an intramolecular version gave atropisomeric lactam derivatives with high optical purity (92−98% ee). The α-alkylation with the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides proceeded with high diastereoselectivity (diastereomer ratio=31:1-80:1).On the other hand, 5-endo-hydroaminocyclization of achiral ortho-alkynylanilines using (R)-SEGPHOS-PdCl2 catalyst afforded optically active atropisomeric indole derivatives (up to 83% ee) in good yields.

Highly Enantioselective Synthesis of Atropisomeric Anilide Derivatives Through Catalytic Asymmetric N‐Arylation: Conformational Analysis and Application to Asymmetric Enolate Chemistry.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Highly Enantioselective Synthesis of Atropisomeric Anilide Derivatives through Catalytic Asymmetric N-Arylation: Conformational Analysis and Application to Asymmetric Enolate Chemistry

In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)(2) catalyst, N-arylation (aromatic amination) of various o-tert-butylanilides with p-iodonitrobenzene proceeds with high enantioselectivity (88-96% ee) to give atropisomeric N-(p-nitrophenyl)anilides having an N-C chiral axis in good yields. Atropisomeric anilide products highly prefer to exist as the E-rotamer which has trans-disposed o-tert-butylphenyl group and carbonyl oxygen. The application of the present catalytic enantioselective N-arylation to an intramolecular version gives atropisomeric lactam derivatives with high optical purity (92-98% ee). The reaction of the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides gives alpha-alkylated products with high diastereoselectivity (diastereomer ratio = 13:1 to 46:1).

Efficient Synthesis of Optically Active Atropisomeric Anilides Through Catalytic Asymmetric N‐Arylation Reaction.

In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation of ortho-tert-butyl-NH-anilides with 4-nitroiodobenzene proceeds with high enantioselectivity (89−95% ee) to give optically active atropisomeric anilides possessing N−C chiral axis. Furthermore, the intramolecular version of the present catalytic asymmetric N-arylation gave atropisomeric lactams with high optical purity (94−96% ee).

Efficient Synthesis of Optically Active Atropisomeric Anilides through Catalytic Asymmetric N-Arylation Reaction [J. Am. Chem. Soc. 2005, 127, 3676−3677

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionEfficient Synthesis of Optically Active Atropisomeric Anilides through Catalytic Asymmetric N-Arylation Reaction [J. Am. Chem. Soc. 2005, 127, 3676−3677].Osamu Kitagawa, Masashi Takahashi, Masatoshi Yoshikawa, and Takeo TaguchiCite this: J. Am. Chem. Soc. 2005, 127, 18, 6910Publication Date (Web):April 19, 2005Publication History Published online19 April 2005Published inissue 1 May 2005https://doi.org/10.1021/ja051606wCopyright © 2005 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views628Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (11 KB) Get e-Alerts Get e-Alerts

Efficient Synthesis of Optically Active Atropisomeric Anilides through Catalytic Asymmetric N-Arylation Reaction

In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation of ortho-tert-butyl-NH-anilides with 4-nitroiodobenzene proceeds with high enantioselectivity (89-95% ee) to give optically active atropisomeric anilides possessing N-C chiral axis. Furthermore, the intramolecular version of the present catalytic asymmetric N-arylation gave atropisomeric lactams with high optical purity (94-96% ee).

Synthesis of Optically Active Atropisomeric Anilide Derivatives through Diastereoselective N-Allylation with a Chiral Pd−π-Allyl Catalyst

N-Allylation of o-tert-butyl anilides derived from o-tert-butyl aniline and (S)-lactic acid or (S)-mandelic acid proceeded with high diastereoselectivity in the presence of a (BINAP)Pd-pi-allyl catalyst to give atropisomeric N-allyl o-tert-butyl anilide derivatives.

Catalytic Asymmetric Synthesis of Optically Active Atropisomeric Anilides Through Enantioselective N‐Allylation with Chiral Pd‐tol‐BINAP Catalyst.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic asymmetric synthesis of optically active atropisomeric anilides through enantioselective N-allylation with chiral Pd-tol-BINAP catalyst.

Catalytic asymmetric N-allylation reaction of ortho-tert-butylanilide derivatives with diallyl carbonate proceeds in the presence of tol-BINAP-Pd catalyst to give chiral N-allyl ortho-tert-butylanilides of 32-44%ee in excellent chemical yields (> or = 90%).

ChemInform Abstract: Synthesis of Optically Active Atropisomeric Anilide Derivatives and Their Application to Asymmetric Reaction

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

光学活性アトロプ異性アニリド誘導体の合成と不斉反応への応用

N-Substituted anilide derivatives bearing a large substitutent such as a tent-Bu group at the ortho-position have atropisomerism due to the high rotation barrier of the N-Ar bond and resist racemization. We have succeeded in the synthesis of such atropisomeric N-Ar amides, imides and lactams with high optically purity and definite absolute configuration, and the development of various asymmetric reactions using them. Furthermore, catalytic asymmetric reaction with such atropisomeric anilide as a chiral ligand is also described.