24331-94-0Relevant articles and documents
The Synthesis of N-Heterocycles using ortho-Metallated Primary Benzylamine Complexes of Palladium(II) and Platinum(II)
O'Sullivan, Richard D.,Parkins, Adrian W.
, p. 1165 - 1166 (1984)
The synthesis of the isoindolinimines (5) by the insertion of isocyanides into the metal-carbon bond of the ortho-palladated primary benzylamine complex (1a) is described; the novel oxidative addition and subsequent reductive elimination of the ortho-metallated primary benzylamine-platinum complex (6) yields 3-oxo-1,2,3,4-tetrahydroisoquinoline (8).
Utilization of Borane-Catalyzed Hydrosilylation as a Dearomatizing Tool: Six-Membered Cyclic Amidine Synthesis from Isoquinolines and Pyridines
Cao, Vinh Do,Jo, Dong Geun,Kim, Huiae,Kim, Changeun,Yun, Seula,Joung, Seewon
, p. 754 - 764 (2021)
In this study, a convenient strategy to synthesize six-membered?? cyclic amidines from isoquinolines and pyridines has been developed. Borane-catalyzed hydrosilylation of each N-heteroarene was utilized as a dearomatizing tool. Substrate scope is broad with respect to both isoquinolines and pyridines, with various reaction pathways depending on the substitution pattern of the N-heteroarenes. The reaction mechanism and reactivity of each class of N-heteroarenes has been discussed. The resulting six-membered (Z)-sulfonyl amidine products are rarely reported and are mostly unprecedented. The scalability of this method and versatility of the cyclic amidine products are also presented.
Synthetic approaches to N- and 4-substituted 1,4-dihydro-3(2H)-isoquinolinone derivatives
O’ Sullivan, Michael J.,Hatley, Richard J.D.,Wellaway, Christopher R.,Bew, Sean P.,Richards, Christopher J.
, (2021/10/14)
Reaction of methyl-2-(2-formylphenyl)acetate with primary amines in a reductive amination/cyclisation process resulted in N-substituted 1,4-dihydro-3(2H)-isoquinolinones. With H2NCH2R sodium borohyride is a suitable reductant (11 examples), but H2NCHR1R2 required a transfer hydrogenation using ammonium formate catalysed by palladium on carbon (9 examples). 4-Substituted-1,4-dihydro-3(2H)-isoquinolinones were synthesised by deprotonation (n-butyllithium) and addition of R3CH2Br (12 examples with R3 = alkyl, Ar, CH[dbnd]CH2, C[tbnd]CH). Modest diastereoselectivity was achieved with 1,4-dihydro-3(2H)-isoquinolinones derived from H2NCHMeR2 [R2 = (η5-C5H4)Co(η4-C4Ph4) - max. dr = 1.9 : 1], but use of H2NCHMeFc (Fc = ferrocenyl) provided a new method of 1,4-dihydro-3(2H)-isoquinolinone N-deprotection with formic acid.
Rapid and Mild Lactamization Using Highly Electrophilic Triphosgene in a Microflow Reactor
Fuse, Shinichiro,Komuro, Keiji,Otake, Yuma,Masui, Hisashi,Nakamura, Hiroyuki
supporting information, p. 7525 - 7532 (2021/03/17)
Lactams are cyclic amides that are indispensable as drugs and as drug candidates. Conventional lactamization includes acid-mediated and coupling-agent-mediated approaches that suffer from narrow substrate scope, much waste, and/or high cost. Inexpensive, less-wasteful approaches mediated by highly electrophilic reagents are attractive, but there is an imminent risk of side reactions. Herein, a methods using highly electrophilic triphosgene in a microflow reactor that accomplishes rapid (0.5–10 s), mild, inexpensive, and less-wasteful lactamization are described. Methods A and B, which use N-methylmorpholine and N-methylimidazole, respectively, were developed. Various lactams and a cyclic peptide containing acid- and/or heat-labile functional groups were synthesized in good to high yields without the need for tedious purification. Undesired reactions were successfully suppressed, and the risk of handling triphosgene was minimized by the use of microflow technology.
Desymmetrization of Prochiral Cyclopentenes Enabled by Enantioselective Palladium-Catalyzed Oxidative Heck Reaction
Chen, Guihua,Cao, Jian,Wang, Qian,Zhu, Jieping
supporting information, p. 322 - 325 (2020/01/02)
In the presence of a catalytic amount of Pd(TFA)2 and a chiral Pyox ligand under oxygen atmosphere, oxidative Heck reaction between arylboronic acids and 4-substituted or 4,4-disubstituted cyclopent-1-enes afforded the chiral arylated products with concurrent creation of two stereocenters in good yields with excellent diastereo- and enantioselectivities.
An Efficient Two-Step Preparation of α-, β-, γ- or δ-Amino Acids from 2-Pyrazinones, 2-Hydroxypyrimidines or 2-Pyridones Respectively
Zacharie, Boulos,Abbott, Shaun D.,Baigent, Christopher B.,Doyle, Christopher,Yalagala, Ravi Shekar
, p. 6486 - 6493 (2018/11/23)
A practical and efficient two-step procedure is reported for the preparation of a variety of α-, β-, γ- and δ-amino acids from 2-pyridone, 2-pyrazinone or 2-hydroxypyrimidine and derivatives. The procedure is amenable to scale-up and in most cases no chromatographic purification of the product is required. This approach is useful, especially in the synthesis of amino acids or deuterated amino acids that are not obtained by other methods.
Copper(I)-catalyzed enantioselective incorporation of ketones to cyclic hemiaminals for the synthesis of versatile alkaloid precursors
Shi, Shi-Liang,Wei, Xiao-Feng,Shimizu, Yohei,Kanai, Motomu
supporting information, p. 17019 - 17022,4 (2012/12/12)
A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Bronsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids.
Copper(I)-catalyzed enantioselective incorporation of ketones to cyclic hemiaminals for the synthesis of versatile alkaloid precursors
Shi, Shi-Liang,Wei, Xiao-Feng,Shimizu, Yohei,Kanai, Motomu
supporting information, p. 17019 - 17022 (2013/01/15)
A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Bronsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids.
Synthesis and evaluation of novel aromatic substrates and competitive inhibitors of GABA aminotransferase
Clift, Michael D.,Silverman, Richard B.
, p. 3122 - 3125 (2008/12/22)
The design, synthesis, and evaluation of novel γ-aminobutyric acid aminotransferase (GABA-AT) inhibitors and inactivators can lead to the discovery of new GABA-related therapeutics. To this end, a series of aromatic amino acid compounds was synthesized to aid in the design of new inhibitors and inactivators of GABA-AT. All compounds were tested as competitive inhibitors of GABA-AT. The amino acids with benzylic amines were also tested as substrates for GABA-AT. It was found that these compounds were all poor competitive inhibitors of GABA-AT, but some were substrates of the enzyme, suggesting their utility as scaffolds for potential GABA-AT mechanism-based inactivators. Computer modeling was used to rationalize the substrate activity of the various compounds.
Superacidic activation of 1- and 3-isoquinolinols and their electrophilic reactions
Koltunov, Konstantin Yu.,Prakash, G. K. Surya,Rasul, Golam,Olah, George A.
, p. 8943 - 8951 (2007/10/03)
Isomeric 1- and 3-isoquinolinols (11 and 12) when activated in CF3SO3H-SbF5 acid system undergo selective ionic hydrogenation with cyclohexane to give 5,6,7,8-tetrahydro-1(2H)- and 5,6,7,8-tetrahydro-3(2H)-isoquinolinones (22 and 27). Under the influence of aluminum chloride similar products were also obtained along with 3,4-dihydro-1(2H)- and 1,4-dihydro-3(2H)-isoquinolinones (23 and 28), respectively. Compounds 11 and 12 also condense with benzene in the presence of aluminum halides, under mild conditions, to give 3,4-dihydro-3-phenyl-1(2H)- and 1,4-dihydro-1-phenyl-3(2H)-isoquinolinones (24 and 29), respectively. Prolonged reaction time or catalysis under strongly acidic HBr-AlBr3 provides an alternative reaction pathway to yield 5,6-dihydro-6,8-diphenyl-1(2H)- and 5,6,7,8-tetrahydro-6,8-diphenyl-3(2H)-isoquinolinones (25 and 30), respectively. Products 24 and 29 were also found to revert back to 11 and 12 in the presence of aluminum halides in o-dichlorobenzene. The mechanism of these intriguing reactions, which involves superelectrophilic dicationic intermediates, is discussed.
