Rapid Ti(Oi-Pr)4 facilitated synthesis of α,α,α-trisubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions

Wang, Ruifang; Gregg, Brian T.; Zhang, Wei; Golden, Kathryn C.; Quinn, John F.; Cui, Peng; Tymoshenko, Dmytro O.

doi:10.1016/j.tetlet.2009.09.178

Cited by 19 publications

(20 citation statements)

References 23 publications

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“…On the other hand, tetrahydropyridine derivatives were the main products when allyl Grignard reagents were reacted with aromatic nitriles . The use of very harsh conditions, microwave heating, and Lewis acids such as titanium alkoxides somewhat expanded the scope of the reaction so as to include two different organometallic nucleophiles and less reactive nitriles . Aside from some exceptions, however, chemical yields and selectivities were generally modest, and long reaction times (up to 24 h) were usually required for the second addition …”

Section: Methodsmentioning

confidence: 99%

Unprecedented Nucleophilic Additions of Highly Polar Organometallic Compounds to Imines and Nitriles Using Water as a Non‐Innocent Reaction Medium

et al. 2017

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In contrast to classic methods carried out under inert atmospheres with dry volatile organic solvents and often low temperatures, the addition of highly polar organometallic compounds to non‐activated imines and nitriles proceeds quickly, efficiently, and chemoselectively with a broad range of substrates at room temperature and under air with water as the only reaction medium. Secondary amines and tertiary carbinamines are furnished in yields of up to and over 99 %. The significant solvent D/H isotope effect observed for the on‐water nucleophilic additions of organolithium compounds to imines suggests that the on‐water catalysis arises from proton transfer across the organic–water interface. The strong intermolecular hydrogen bonds between water molecules may play a key role in disfavoring protonolysis, which occurs extensively in other protic media such as methanol. This work lays the foundation for reshaping many fundamental s‐block metal‐mediated organic transformations in water.

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Section: Methodsmentioning

confidence: 99%

Unprecedented Nucleophilic Additions of Highly Polar Organometallic Compounds to Imines and Nitriles Using Water as a Non‐Innocent Reaction Medium

et al. 2017

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“…Product was purified by acid/base workup and recovered as a colorless oil (0.44 g, 79% yield), which was found to match the data in literature. 6 1 H NMR (400 MHz, CDCl 3 ) δ 7.47 -7.39 (m, 1H), 7.21 (ddd, J = 9.8, 7.6, 3.3 Hz, 1H), 7.12 -7.06 (m, 1H), 7.05 -6.98 (m, 1H), 1.79 (s, 2H). 19 F NMR (376 Hz, CDCl3), -120.…”

Section: -(2-fluorophenyl)propan-2-amine (S-3)mentioning

confidence: 99%

“…Product was purified on silica gel in CH 2 Cl 2 /MeOH (98:2) and recovered as a yellow oil (0.61 g, 92% yield). 1 H NMR (600 MHz, CDCl 3 ) δ 7.39 (t, J = 8.2 Hz, 1H), 7.20 -7.17 (m, 1H), 7.07 (t, J = 7.6 Hz, 1H), 6.98 (dd, J = 12.8, 8.1 Hz, 1H), 1.88 (td, J = 13.3, 4.9 Hz, 1H), 1.77 -1.72 (m, 1H), 1.49 (s, 3H), 1.15 -1.06 (m, 2H), 0.84 (t, J = 7.4 Hz, 3H). 13 equiv.)…”

Section: -(2-fluorophenyl)pentan-2-amine (S-5)mentioning

confidence: 99%

“…Product was purified by acid/base workup and recovered as a yellow oil (0.51 g, 74% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 7.43 -7.38 (m, 1H), 7.22 -7.17 (m, 1H), 7.08 (td, J = 7.6, 1.3 Hz, 1H), 6.99 (ddd, J = 12.8, 8.1, 1.3 Hz, 1H), 1.95 -1.87 (m, 1H), 1.81 -1.73 (m, 3H), 1.50 (s, 3H), 1.28 -1.20 (m, 2H), 1.12 -1.01 (m, 2H), 0.83 (t, J = 7.3 Hz, 3H). 13…”

Section: -(2-fluorophenyl)pentan-2-amine (S-5)mentioning

confidence: 99%

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Carbon Dioxide-Mediated C(sp2)–H Arylation of Primary and Secondary Benzylamines

Kapoor¹,

Chand-Thakuri²,

Young³

2018

Preprint

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Carbon-carbon bond formation by transition metal-catalyzed C–H activation has become an important strategy to fabricate new bonds in a rapid fashion. Despite the pharmacological importance of ortho-arylbenzylamines, however, effective ortho-C–C bond formation from C–H bond activation of free primary and secondary benzylamines using PdII remains an outstanding challenge. Presented herein is a new strategy for constructing ortho-arylated primary and secondary benzylamines mediated by carbon dioxide (CO2). The use of CO2 is critical to allowing this transformation to proceed under milder conditions than previously reported, and that are necessary to furnish free amine products that can be directly used or elaborated without the need for deprotection. In cases where diarylation is possible, a chelate effect is demonstrated to facilitate selective monoarylation.

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“…Fatty amines are important raw materials in the oleochemical industry, and they are intermediates in the production of cationic surfactants [7,8]. Amines have been synthesized from the amination of alcohols [9] and of alkyl halides [10] as well as from the reduction of amides [11] and of nitriles [12]. Further, functionalized amines such as epoxy fatty amines are useful intermediates in the production of industrial products such as polymers [13,14].…”

Section: Introductionmentioning

confidence: 99%

Vernonia Oil: Conversion to a Mixture of Tertiary Amines Including N,N‐Dimethyl‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl Amine

Johnson¹,

Ayorinde²

2011

J Americ Oil Chem Soc

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Vernonia galamensis is a new potential industrial oilseed crop found in tropical Africa. It is the source of a naturally epoxidized oil called vernonia oil (VO) which is extracted from the seed of the plant. In this study VO was used as the starting material for the synthesis of a mixture of amines, with the major product amine being N,N-dimethyl-(12S,13R)-epoxy-cis-9-octadecenyl amine. VO was transesterified via a base catalyzed methanolysis using sodium methoxide to yield VO methyl esters (VOME). Aminolysis of the VOME with dimethylamine as reagent and solvent under reflux conditions afforded the tertiary amides, with N,N-dimethyl-(12S,13R)-epoxy-cis-9-octadecenyl amide as the major product. The mixture was then subjected to metal hydride reduction with lithium aluminum hydride in diethylether under reflux conditions to obtain the desired amine mixture including N,N-dimethyl-(12S,13R)-epoxycis-9-octadecenyl amine. Electron impact mass spectrometry was used to characterize the mixture of amines. Additionally, proton NMR, 13 C NMR, and FTIR were used for characterization of N,N-dimethyl-(12S,13R)-epoxy-cis-9-octadecenyl amine. To further confirm the conversion of VO to the amines, the quaternary ammonium salts were synthesized and characterized by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

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Rapid Ti(Oi-Pr)4 facilitated synthesis of α,α,α-trisubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions

Cited by 19 publications

References 23 publications

Unprecedented Nucleophilic Additions of Highly Polar Organometallic Compounds to Imines and Nitriles Using Water as a Non‐Innocent Reaction Medium

Unprecedented Nucleophilic Additions of Highly Polar Organometallic Compounds to Imines and Nitriles Using Water as a Non‐Innocent Reaction Medium

Carbon Dioxide-Mediated C(sp2)–H Arylation of Primary and Secondary Benzylamines

Vernonia Oil: Conversion to a Mixture of Tertiary Amines Including N,N‐Dimethyl‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl Amine

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