28897-81-6Relevant articles and documents
Implementation of the Dakin-West reaction for the preparation of an α-amino-pentafluoroethyl ketone
Curran, Timothy T.
, p. 107 - 112 (1995)
We have successfully implemented the Dakin-West reaction to prepare 4-(carbamoyl- or benzoylamino)-5-methyl-1,1,1,2,2-pentafluorohexan-3-one (3, 7a and 7b).We also isolated and characterized the impurities obtained from this Dakin-West reaction.Although w
Base-catalysed 18F-labelling of trifluoromethyl ketones. Application to the synthesis of 18F-labelled neutrophil elastase inhibitors
Meyer, Denise N.,Cortés González, Miguel A.,Jiang, Xingguo,Johansson-Holm, Linus,Pourghasemi Lati, Monireh,Elgland, Mathias,Nordeman, Patrik,Antoni, Gunnar,Szabó, Kálmán J.
, p. 8476 - 8479 (2021/09/02)
A new method for the fluorine-18 labelling of trifluoromethyl ketones has been developed. This method is based on the conversion of a-COCF3 functional group to a difluoro enol silyl ether followed by halogenation and fluorine-18 labelling. The utility of this new method was demonstrated by the synthesis of fluorine-18 labelled neutrophil elastase inhibitors, which are potentially useful for detection of inflammatory disorders.
Palladium-catalyzed asymmetric decarboxylative allylation of azlactone enol carbonates: Fast access to enantioenriched α-allyl quaternary amino acids
Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,De Lorenzi, Ersilia,Colombo, Lino
, p. 732 - 741 (2019/01/09)
We report a fast protocol for the synthesis of enantioenriched quaternary 4-allyl oxazol-5-ones. The key step is a Pd-catalyzed enantioselective Tsuji allylation of azlactone allyl enol carbonates, which can be easily prepared starting from racemic α-amino acids. The use of (R,R)-DACH-phenyl Trost chiral ligand allowed the attainment of the allylated derivatives in very good yields (83–98 %) and with ee up to 85 %. Scaling up the allylation protocol to gram quantities did not affect the yields end ee values. The produced 4-allyl azlactones can be converted into the corresponding quaternary amino acids or submitted to further synthetic elaborations exploiting the allyl moiety as a handle for the attachment of alkyl and aryl groups. After hydrolysis of the azlactone ring, the zwitterionic amino acids can be attained in enantiopure or nearly optically pure form through only one recrystallization step.
Transformation of Racemic Azlactones into Enantioenriched Dihydropyrroles and Lactones Enabled by Hydrogen-Bond Organocatalysis
?abka, Matej,Kocian, Adrián,Bilka, Stanislav,Andrej?ák, Samuel,?ebesta, Radovan
, p. 6077 - 6087 (2019/09/12)
Azlactones, a potent building block for the synthesis of complex molecules, have been explored in an organocatalytic Mannich reaction with protected imines. In this study, azlactones containing a propargyl substituent were employed for the first time in organocatalysis so far. The catalytically active species responsible for high enantioselectivity with substrate containing such a small linear substituent is assembled in situ from a bifunctional thiourea, prone to dimerization, and an organic acid, as evidenced by DOSY NMR. The resulting α,β-diamino acid derivatives were subjected to further derivatization: as an example, gold-catalyzed intramolecular hydroamination of alkynes gave chiral spirocyclic dihydropyrrole. Alternatively, related squaramide catalyst enabled a Mannich reaction of azlactones with N-aryl or alkyl glyoxylate imines. Reduction of these adducts gave access to 2,3-diaminobutyrolactones or 2,3-diamino-1,4-diol with a tertiary and a quaternary stereocenter.
Metal-Free Insertion Reactions of Diazo Carbonyls to Azlactones
De Mello, Amanda C.,Momo, Patrícia B.,Burtoloso, Antonio C. B.,Amarante, Giovanni W.
, p. 11399 - 11406 (2018/09/12)
Insertion reactions of diazo carbonyls to azlactones in basic conditions have been performed. The developed method allows the preparation of a wide range of oxazole derivatives in yields ranging from 74 to 98%. Different substituents on both azlactone rings and diazo carbonyls do not compromise the methodology, even those containing stereogenic centers. Isotopic labeling experiments revealed the mechanism may proceed through a rare diazo carbonyl activation by an ammonium salt derivative.
Group-Assisted Purification Chemistry for Asymmetric Mannich-type Reaction of Chiral N-Phosphonyl Imines with Azlactones Leading to Syntheses of α-Quaternary α,β-Diamino Acid Derivatives ?
Zhang, Haowei,Yang, Zhen,Zhao, Brian Nlong,Li, Guigen
, p. 644 - 655 (2018/01/27)
An asymmetric Mannich-type reaction between chiral N-phosphonyl imines and azlactones [oxazol-5(4H)-ones] has been established under convenient conditions at room temperature. The reaction was performed without using any bases, additives, or catalysts to achieve up to excellent chemical yields and diastereoselectivity for 32 examples. The α-quaternary syn-α,β-diamino acid products were purified simply by washing the crude mixtures with cosolvents, following the group-assisted purification chemistry/technology, without involving traditional chromatography or recrystallization methods. The auxiliary can be readily removed and recycled for reuse. The absolute configuration was unambiguously assigned by X-ray structural analysis.
One-Pot Vinylation of Azlactones: Fast Access to Enantioenriched α-Vinyl Quaternary Amino Acids
Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,Colombo, Lino
, p. 2964 - 2970 (2017/06/06)
We report a fast one-pot protocol for the direct vinylation of azlactones [oxazol-5-(4H)-ones] by using as a key step an aldol addition with 2-(phenylselenenyl)acetaldehyde followed by dehydroxyselenation. The acid hydrolysis of the oxazolone ring gave the desired fully deprotected α-vinyl quaternary α-amino acids in almost quantitative yields. An enantioselective variant of the method was also developed by using catalytic chiral bases. The use of Sharpless ligand (DHQD)2PHAL produced the final quaternary amino acids in good overall yields (62–78 %) and with ee values up to 86 %. Scaling up the optimized protocol to gram quantities did not affect the yields and ee values. We also demonstrated that the vinyl moiety installed onto the oxazolone ring can be exploited as a handle for the attachment of aryl groups through a Heck coupling reaction.
Peptide-catalyzed conversion of racemic oxazol-5(4 H)-ones into enantiomerically enriched α-amino acid derivatives
Metrano, Anthony J.,Miller, Scott J.
, p. 1542 - 1554 (2014/03/21)
We report the development and optimization of a tetrapeptide that catalyzes the methanolytic dynamic kinetic resolution of oxazol-5(4H)-ones (azlactones) with high levels of enantioinduction. Oxazolones possessing benzylic-type substituents were found to perform better than others, providing methyl ester products in 88:12 to 98:2 er. The mechanism of this peptide-catalyzed process was investigated through truncation studies and competition experiments. High-field NOESY analysis was performed to elucidate the solution-phase structure of the peptide, and we present a plausible model for catalysis.
Enantioselective construction of tetrasubstituted stereogenic carbons through bronsted base catalyzed michael reactions: α′-hydroxy enones as key enoate equivalent
Badiola, Eider,Fiser, Bla,Gmez-Bengoa, Enrique,Mielgo, Antonia,Olaizola, Iurre,Urruzuno, Iaki,Garca, Jess M.,Odriozola, Jos M.,Razkin, Jess,Oiarbide, Mikel,Palomo, Claudio
, p. 17869 - 17881 (2015/02/19)
Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Bronsted base (BB) catalysis and the use of α′-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α′-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α′-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.
BENZAMIDE TRPA1 ANTAGONISTS
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Page/Page column 44, (2014/12/12)
Compounds of formula I, pharmaceutically acceptable salts thereof, diastereomers, enantiomers, or mixtures thereof: wherein R, X, Y, Z, n and A are as defined in the specification, as well as pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
