63991-66-2Relevant academic research and scientific papers
2:1 versus 1:1 Coupling of Alkylacetylenes with Secondary Amines: Selectivity Switching in 8-Quinolinolato Rhodium Catalysis
Morimoto, Yoshihiko,Hamada, Moe,Takano, Shotaro,Mochizuki, Katsufumi,Kochi, Takuya,Kakiuchi, Fumitoshi
, p. 3803 - 3808 (2021/04/05)
Both 2:1 and 1:1 couplings of alkylacetylenes with secondary amines were achieved using 8-quinolinolato rhodium catalysts and CsF. The 2:1/1:1 selectivity was switched by choosing the reaction solvent. In DMA, an unprecedented 2:1 coupling reaction of alkylacetylenes with amines proceeded to give 2-aminodiene products. One-pot 2:1 coupling/reduction provided rapid access to various allylamines, while one-pot coupling/hydrolysis gave enones as products. In toluene, anti-Markovnikov hydroamination occurred under relatively mild conditions to give 1:1 coupling products.
High-Throughput Screening of Reductive Amination Reactions Using Desorption Electrospray Ionization Mass Spectrometry
Cooks, R. Graham,Ferreira, Christina R.,Li, Yangjie,Logsdon, David L.,Paschoal Sobreira, Tiago Jose,Thompson, David H.
supporting information, p. 1647 - 1657 (2020/10/26)
This study describes the latest generation of a high-throughput screening system that is capable of screening thousands of organic reactions in a single day. This system combines a liquid handling robot with desorption electrospray ionization (DESI) mass spectrometry (MS) for a rapid reaction mixture preparation, accelerated synthesis, and automated MS analysis. A total of 3840 unique reductive amination reactions were screened to demonstrate the throughputs that are capable with the system. Products, byproducts, and intermediates were all monitored in full-scan mass spectra, generating a complete view of the reaction progress. Tandem mass spectrometry experiments were conducted to verify the identity of the products formed. The amine and electrophile reactivity trends represented in the data match what is expected from theory, indicating that the system accurately models the reaction performance. The DESI results correlated well with those generated using more traditional mass spectrometry techniques like liquid chromatography-mass spectrometry, validating the data generated by the system.
Contra-thermodynamic Hydrogen Atom Abstraction in the Selective C-H Functionalization of Trialkylamine N-CH3 Groups
Barham, Joshua P.,John, Matthew P.,Murphy, John A.
supporting information, p. 15482 - 15487 (2016/12/09)
We report a simple one-pot protocol that affords functionalization of N-CH3 groups in N-methyl-N,N-dialkylamines with high selectivity over N-CH2R or N-CHR2 groups. The radical cation DABCO+?, prepared in situ by oxidation of DABCO with a triarylaminium salt, effects highly selective and contra-thermodynamic C-H abstraction from N-CH3 groups. The intermediates that result react in situ with organometallic nucleophiles in a single pot, affording novel and highly selective homologation of N-CH3 groups. Chemoselectivity, scalability, and recyclability of reagents are demonstrated, and a mechanistic proposal is corroborated by computational and experimental results. The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure-activity relationships.
Esters, Including Triglycerides, and Hydrogen as Feedstocks for the Ruthenium-Catalyzed Direct N-Alkylation of Amines
Adam, Rosa,Cabrero-Antonino, Jose R.,Junge, Kathrin,Jackstell, Ralf,Beller, Matthias
supporting information, p. 11049 - 11053 (2016/10/13)
Triglycerides are used for the direct N-alkylation of amines with molecular hydrogen for the first time. A broad range of interesting and industrially relevant secondary and tertiary amines are obtained in the presence of an in situ formed Ru/Triphos complex. Notably, plant oil can be efficiently applied in this single-step process. Moreover, a variety of other methyl esters can be used as N-alkylation agents in the presence of hydrogen for the synthesis of more advanced building blocks.
Neutral zwitterionic displacer molecules for hydrophobic displacement chromatography
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, (2015/09/23)
A process for separating organic compounds from a mixture by reverse-phase displacement chromatography, including providing a hydrophobic stationary phase; applying to the hydrophobic stationary phase a mixture comprising organic compounds to be separated; displacing the organic compounds from the hydrophobic stationary phase by applying thereto an aqueous composition comprising a non-surface active hydrophobic neutral zwitterionic displacer molecule and optionally an organic solvent; and collecting a plurality of fractions eluted from the hydrophobic stationary phase containing the separated organic compounds; in which the non-surface active hydrophobic neutral zwitterionic displacer molecule comprises a hydrophobic zwitterion having the general formula, as defined in the disclosure: [CM-R*—CM′].
NEUTRAL ZWITTERIONIC DISPLACER MOLECULES FOR HYDROPHOBIC DISPLACEMENT CHROMATOGRAPHY
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Page/Page column, (2014/09/29)
A process for separating organic compounds from a mixture by reverse-phase displacement chromatography, including providing a hydrophobic stationary phase; applying to the hydrophobic stationary phase a mixture comprising organic compounds to be separated; displacing the organic compounds from the hydrophobic stationary phase by applying thereto an aqueous composition comprising a non-surface active hydrophobic neutral zwitterionic displacer molecule and optionally an organic solvent; and collecting a plurality of fractions eluted from the hydrophobic stationary phase containing the separated organic compounds; in which the non-surface active hydrophobic neutral zwitterionic displacer molecule comprises a hydrophobic zwitterion having the general formula, as defined in the disclosure: [CM-R*—CM′].
Direct nucleophilic addition to N-alkoxyamides
Yanagita, Yuta,Nakamura, Hugh,Shirokane, Kenji,Kurosaki, Yusuke,Sato, Takaaki,Chida, Noritaka
supporting information, p. 678 - 684 (2013/04/10)
While the synthesis of amide bonds is now one of the most reliable organic reactions, functionalization of amide carbonyl groups has been a long-standing issue due to their high stability. As an ongoing program aimed at practical transformation of amides, we developed a direct nucleophilic addition to N-alkoxyamides to access multisubstituted amines. The reaction enabled installation of two different functional groups to amide carbonyl groups in one pot. The N-alkoxy group played important roles in this reaction. First, it removed the requirement for an extra preactivation step prior to nucleophilic addition to activate inert amide carbonyl groups. Second, the N-alkoxy group formed a five-membered chelated complex after the first nucleophilic addition, resulting in suppression of an extra addition of the first nucleophile. While diisobutylaluminum hydride (DIBAL-H) and organolithium reagents were suitable as the first nucleophile, allylation, cyanation, and vinylation were possible in the second addition including inter- and intramolecular reactions. The yields were generally high, even in the synthesis of sterically hindered α-trisubstituted amines. The reaction exhibited wide substrate scope, including acyclic amides, five- and six-membered lactams, and macrolactams. Copyright
The "borrowing hydrogen strategy" by supported ruthenium hydroxide catalysts: Synthetic scope of symmetrically and unsymmetrically substituted amines
Yamaguchi, Kazuya,He, Jinling,Oishi, Takamichi,Mizuno, Noritaka
scheme or table, p. 7199 - 7207 (2010/09/05)
The N-alkylation of ammonia (or its surrogates, such as urea, NH 4HCO3, and (NH4)2CO3) and amines with alcohols, including primary and secondary alcohols, was efficiently promoted under anaerobic conditions by the easily prepared and inexpensive supported ruthenium hydroxide catalyst Ru(OH)x/TiO2. Various types of symmetrically and unsymmetrically substituted "tertiary" amines could be synthesized by the N-alkylation of ammonia (or its surrogates) and amines with "primary" alcohols. On the other hand, the N-alkylation of ammonia surrogates (i.e., urea and NH 2HCO3) with "secondary" alcohols selectively produced the corresponding symmetrically substituted "secondary" amines, even in the presence of excess amounts of alcohols, which is likely due to the steric hindrance of the secondary alcohols and/or secondary amines produced. Under aerobic conditions, nitriles could be synthesized directly from alcohols and ammonia surrogates . The observed catalysis for the present N-alkylation recations was intrinsically heterogeneous, and the retrieved catalyst could be reused without any significant loss of catalytic performance. The present catalytic transformation would proceed through consecutive N-alkylation reactions, in which alcohols act as alkylating reagents. On the basis of deuterium-labeling experiments, the formation of the ruthenium dihydride species is suggested during the N-alkylation reactions.
Cp*Ir-catalyzed N-alkylation of amines with alcohols. A versatile and atom economical method for the synthesis of amines
Fujita, Ken-ichi,Enoki, Youichiro,Yamaguchi, Ryohei
, p. 1943 - 1954 (2008/09/17)
A versatile and highly atom economical catalytic system consisting of [Cp*IrCl2]2/NaHCO3 (Cp*=pentamethylcyclopentadienyl) for the N-alkylation of amines with primary and secondary alcohols as alkylating reagents has been developed. For example, the reaction of equimolar amounts of aniline and benzyl alcohol in the presence of [Cp*IrCl2]2 (1.0 mol % Ir) and NaHCO3 (1.0 mol %) in toluene at 110 °C gives N-benzylaniline in 94% yield. The present catalytic system is applicable to the N-alkylation of both primary and secondary amines, and only harmless water is produced as co-product. A wide variety of secondary and tertiary amines can be synthesized with high atom economy under mild and less-toxic conditions. One-pot sequential N-alkylation leading to tertiary amines bearing three different substituents is also described.
