100571-64-0Relevant articles and documents
Hydrogen-Bonding-Promoted Cascade Rearrangement Involving the Enlargement of Two Rings: Efficient Access to Polycyclic Quinoline Derivatives
Cao, Wen-Bin,Ji, Shun-Jun,Lan, Yu,Li, Haiyan,Li, Shijun,Xu, Meng-Meng,Xu, Xiao-Ping
, p. 21425 - 21430 (2020)
An efficient cascade reaction of tryptamine-derived isocyanides with C,N-cyclic azomethine imines is described. The polycyclic pyrrolo[2,3-c]quinoline derivatives, which benefited from rearrangement process driven by hydrogen bonding, could be directly assembled in moderate to good yields (40–87 %) under metal-free and mild conditions. This transformation involved four new heterocyclic rings formations and uniquely, ring opening of indole as well as ring expansion of C,N-cyclic azomethine imine. Both experimental and DFT studies provided guidance on the in-depth insight into the reaction pathways and hydrogen bonding was identified to lower the free energy barrier in transition states. This work constitutes a rare example of tryptamine-derived isocyanide-based cascade reactions, and potentially could be a powerful synthetic strategy for accessing polycyclic analogues involved in natural products.
Synthesis of polycyclic spiroindolines by highly diastereoselective interrupted Ugi cascade reactions of 3-(2-isocyanoethyl)indoles
Saya, Jordy M.,Oppelaar, Barry,Cioc, Rǎzvan C.,Van Der Heijden, Gydo,Vande Velde, Christophe M. L.,Orru, Romano V. A.,Ruijter, Eelco
, p. 12482 - 12485 (2016)
We report a highly diastereoselective interrupted Ugi reaction to construct a broad range of structurally congested and stereochemically complex spiroindolines from tryptamine-derived isocyanides. The reaction is facilitated by using fluorinated alcohols (TFE or HFIP) as solvents and tolerates a broad range of amines, aldehydes and 2-isocyanoethylindoles to give polycyclic products in moderate to excellent yields.
A Convergent Approach to Heterocycle Synthesis via Silver Ion Mediated α-Keto Imidoyl Halide-Arene Cyclizations. An Application to the Synthesis of the Erythrinane Skeleton
Westling, Mark,Smith, Richard,Livinghouse, Tom
, p. 1159 - 1165 (1986)
α-Keto imidoyl halides formed by the reaction of representative 2-phenylethyl and related isocyanides with acyl halides undergo facile cyclization induced by silver salts to provide the corresponding heterocycles in good to excellent yield.An efficient synthesis of the erythrinane skeletal system which relies upon the sequential utlization of this method followed by an azomethine ylide cycloaddition reaction is described.
Iodospirocyclization of Tryptamine-Derived Isocyanides: Formal Total Synthesis of Aspidofractinine
Saya, Jordy M.,Roose, Thomas R.,Peek, Jarryt J.,Weijers, Bram,de Waal, Thomas J. S.,Vande Velde, Christophe M. L.,Orru, Romano V. A.,Ruijter, Eelco
, p. 15232 - 15236 (2018)
The N-iodosuccinimide-mediated spirocyclization of tryptamine-derived isocyanides to generate spiroindolenines is reported. The products contain both an imine and an imidoyl iodide as flexible handles for follow-up chemistry. Nucleophilic addition typical
Visible-Light-Induced Trifluoromethylation of Isonitrile-Substituted Indole Derivatives: Access to 1-(Trifluoromethyl)-4,9-dihydro-3H-pyrido[3,4-b]indole and β-Carboline Derivatives
Liu, Jiaxin,Li, Longhai,Yu, Liuzhu,Tang, Lisha,Chen, Qin,Shi, Min
, p. 2959 - 2965 (2018)
A visible-light-induced trifluoromethylation of isonitrile-substituted indole derivatives has been developed from the reaction of isonitrile-substituted indoles with Togni II reagent, affording 1-(trifluoromethyl)-4,9-dihydro-3H-pyrido[3,4-b]indoles in mo
Synthesis of Oxazolidin-2-ones by Oxidative Coupling of Isonitriles, Phenyl Vinyl Selenone, and Water
Buyck, Thomas,Pasche, Delphine,Wang, Qian,Zhu, Jieping
, p. 2278 - 2281 (2016)
Reaction of alkyl isocyanides, phenyl vinyl selenone, and water in the presence of a catalytic amount of Cs2CO3 afforded oxazolidin-2-ones in good yields. This unprecedented heteroannulation process created four chemical bonds in a s
Asymmetric dearomatization of indoles through a Michael/Friedel-Crafts-Type cascade to construct polycyclic spiroindolines
Zhao, Xiaohu,Liu, Xiaohua,Mei, Hongjiang,Guo, Jing,Lin, Lili,Feng, Xiaoming
, p. 4032 - 4035 (2015)
A highly efficient asymmetric dearomatization of indoles was realized through a cascade reaction between 2-isocyanoethylindole and alkylidene malonates catalyzed by a chiral N,N-dioxide/MgII catalyst. Fused polycyclic indolines containing three stereocenters were afforded in good yields with excellent diastereo- and enantioselectivities through a Michael/Friedel-Crafts/Mannich cascade. When 2-substituted 2-isocyanoethylindoles were used, spiroindoline derivatives were obtained through a Michael/Friedel-Crafts reaction.
Continuous-flow synthesis of thioureas, enabled by aqueous polysulfide solution
ábrányi-Balogh, Péter,Keser?, Gy?rgy M.,Mándity, István M.,Németh, András Gy.,Orsy, Gy?rgy,Szabó, Renáta
, (2021/06/25)
We have developed the continuous-flow synthesis of thioureas in a multicomponent reaction starting from isocyanides, amidines, or amines and sulfur. The aqueous polysulfide solution enabled the application of sulfur under homogeneous and mild conditions. The crystallized products were isolated by simple filtration after the removal of the co-solvent, and the sulfur retained in the mother liquid. Presenting a wide range of thioureas synthesized by this procedure confirms the utility of the convenient continuous-flow application of sulfur.
Isocyanide 2.0
Ahmadian-Moghaddam, Maryam,D?mling, Alexander,Patil, Pravin
supporting information, p. 6902 - 6911 (2020/11/09)
The isocyanide functionality due to its dichotomy between carbenoid and triple bond characters, with a nucleophilic and electrophilic terminal carbon, exhibits unusual reactivity in organic chemistry exemplified for example in the Ugi reaction. Unfortunately, the over proportional use of only a few isocyanides hampers novel discoveries about the fascinating reactivity of this functional group. The synthesis of a broad range of isocyanides with multiple functional groups is lengthy, inefficient, and exposes the chemist to hazardous fumes. Here we present an innovative isocyanide synthesis overcoming these problems by avoiding the aqueous workup which we exemplify by parallel synthesis from a 0.2 mmol scale performed in 96-well microtiter plates up to a 0.5 mol multigram scale. The advantages of our methodology include an increased synthesis speed, very mild conditions giving access to hitherto unknown or highly reactive classes of isocyanides, rapid access to large numbers of functionalized isocyanides, increased yields, high purity, proven scalability over 5 orders of magnitude, increased safety and less reaction waste resulting in a highly reduced environmental footprint. For example, the hitherto believed to be unstable 2-isocyanopyrimidine, 2-acylphenylisocyanides and even o-isocyanobenzaldehyde could be accessed on a preparative scale and their chemistry was explored. Our new isocyanide synthesis will enable easy access to uncharted isocyanide space and will result in many discoveries about the unusual reactivity of this functional group. This journal is
Efficient syntheses and anti-cancer activity of xenortides A-D including: Ent / epi -stereoisomers
Esmati,Maddirala,Hussein,Amawi,Tiwari,Andreana
, p. 5332 - 5342 (2018/08/03)
A one-pot, two-step, total synthesis of naturally occurring xenortides A, B, C and D, (Xens A-D) isolated from the bacterium Xenorhabdus nematophila, and an entire complementary set of stereoisomers, has been achieved. Compounds were synthesized utilizing an isocyanide-based Ugi 4-CR followed by facile N-Boc deprotection. The reaction sequence took advantage of the chiral pool of N-Boc protected amino acids (l-Leu/Val and d-Leu/Val) with aryl isocyanides, phenyl acetaldehyde and methylamine giving the desired Xens A-D (A and B >98% ee) and all subsequent stereoisomers in reasonable yields upon deprotection followed by separation of diastereomers. Also, detailed mechanistic insights for diastereoselectivity of (-)-Xen A, as a model in the Ugi 4-CR, has been described. Moreover, for the first time, this focused library was screened for cytotoxicity against a panel of epithelial cancer cell lines as well as normal cell lines with an MTT proliferation assay. The structure-activity relationship (SAR) study demonstrated that tryptamides Xen B and D were more active than phenylethylamides Xen A and C. Furthermore, (-)-Xen B (IC50 = 19-25 μM) and ent-(+)-Xen D (IC50 = 21-26 μM) gave the highest cytotoxicity and they were also found to be non-toxic toward normal cells. Importantly, the SAR results indicate that the stereochemistry at C8 and C11 in (-)-Xen B and ent-(+)-Xen D play a critical role in cytotoxic activity.