- A Unified Approach for Divergent Synthesis of Heterocycles via TMSOTf-Catalyzed Formal [3+2] Cycloaddition of Electron-Rich Alkynes
-
We present a synthetic protocol for the construction of polysubstituted five-membered heterocycles via TMSOTf-catalyzed formal [3+2] cycloaddition of electron-rich alkynes, which features free from any metal, atom economy and water as the main by-product. Furthermore, alkenyl ether adduct has been verified as the key intermediate. Notably, by utilizing this approach, we can synthesize a broad range of polysubstituted furans, thiophenes and pyrroles, and extend this transformation to deliver fused-polyheterocycles. This reaction can be achieved on a gram scale and the corresponding products are intermediates for producing diverse potentially useful scaffolds. (Figure presented.).
- Chen, Ping,Cao, Wei,Li, Xiangqian,Shi, Dayong
-
p. 4789 - 4794
(2021/09/02)
-
- Direct oxidation ofN-ynylsulfonamides intoN-sulfonyloxoacetamides with DMSO as a nucleophilic oxidant
-
N-Arylethynylsulfonamides are oxidized intoN-sulfonyl-2-aryloxoacetamides directly and efficiently with dimethyl sulfoxide (DMSO) as both an oxidant and solvent with microwave assistance. DFT calculations indicate that DMSO nucleophilically attacks the ethylic triple bond and transfers its oxygen atom to the triple bond to form zwitterionic anionicN-sulfonyliminiums to trigger the reaction. Then it nucleophilically attacks the generated iminium intermediates to accomplish the oxidationviathe second oxygen atom transfer. The current method provides a straightforward and efficient strategy to transform variousN-arylethynylsulfonamides intoN-sulfonyl-2-aryloxoacetamides, sulfonyl oxoacetimides, without any other electrophilic activators or oxidants.
- Dong, Jun,Fu, Duo,Sheng, Dongning,Wang, Jiayi,Xu, Jiaxi
-
p. 40243 - 40252
(2021/12/31)
-
- Acid-catalyzed [2 + 2 + 2] cycloaddition of two cyanamides and one ynamide: Highly regioselective synthesis of 2,4,6-triaminopyrimidines
-
Triflic acid (10 mol%) catalyzes the highly regioselective [2 + 2 + 2] cycloaddition between two cyanamides and one ynamide to grant the 2,4,6-triaminopyrimidine core. The developed synthetic method is effective for the preparation of a family of the diversely substituted heterocyclic products (30 examples; yields up to 94%). The synthesis can be easily scaled up and conducted in gram quantities. As demonstrated by the post-functionalizations involving the amino-substituents, the obtained heterocycles represent a useful platform for the construction of miscellaneous pyrimidine-based frameworks. The performed density functional theory calculations verified a particular role of H+, functioning as an electrophilic activator, in the regioselectivity of the cycloaddition.
- Dubovtsev, Alexey Yu.,Zvereva, Valeria V.,Shcherbakov, Nikolay V.,Dar'In, Dmitry V.,Novikov, Alexander S.,Kukushkin, Vadim Yu.
-
supporting information
p. 4577 - 4584
(2021/05/31)
-
- Catalyst-Free [4+2] Cycloaddition of Ynamides with 2-Halomethyl Phenols to Construct 2-Amino-4 H-Chromenes and α-Halo Enamides Simultaneously
-
We report the development of a facile protocol for the [4+2] cycloaddition of ynamides and 2-halomethyl phenols to afford the corresponding 2-amino-4H-chromenes and α-halo enamides under catalyst-free conditions. The reaction proceeds under mild condition
- Wen, Hao,Yan, Weibo,Chen, Ping,Li, Yu,Tang, Yu
-
p. 12870 - 12881
(2020/11/02)
-
- Chemo- And regioselective click reactions through nickel-catalyzed azide-alkyne cycloaddition
-
Metal-catalyzed cycloaddition is an expeditious synthetic route to functionalized heterocyclic frameworks. However, achieving reactivity-controlled metal-catalyzed azide-alkyne cycloadditions from competing internal alkynes has been challenging. Herein, we report a nickel-catalyzed [3 + 2] cycloaddition of unsymmetrical alkynes with organic azides to afford functionalized 1,2,3-triazoles with excellent regio- and chemoselectivity control. Terminal alkynes and cyanoalkynes afford 1,5-disubstituted triazoles and 1,4,5-trisubstituted triazoles bearing a 4-cyano substituent, respectively. Thioalkynes and ynamides exhibit inverse regioselectivity compared with terminal alkynes and cyanoalkynes, affording 1,4,5-trisubstituted triazoles with 5-thiol and 5-amide substituents, respectively. Density functional theory calculations are performed for the elucidation of the reaction mechanism. The computed mechanism suggests that a nickellacyclopropene intermediate is generated by the oxidative addition of the alkyne substrate to the Ni(0)-Xantphos catalyst, and the subsequent C-N coupling of this intermediate with an azide is responsible for the chemo- and regioselectivity.
- Baek, Seung-Yeol,Baik, Mu-Hyun,Choe, Wonyoung,Hong, Sung You,Jeon, Ji Hwan,Jeong, Seo Yeong,Kim, Woo Gyum,Nam, Dongsik
-
p. 3374 - 3381
(2020/05/14)
-
- Sulfilimines as Versatile Nitrene Transfer Reagents: Facile Access to Diverse Aza-Heterocycles
-
We herein report the unprecedented synthesis of diverse biologically important aza-heterocycles by employing sulfilimines as nitrene transfer reagents. This class of sulfur-based aza-ylides had not been successfully used for gold nitrene transfer before. This work contains an efficient generation of α-imino gold carbenes by N?S cleavage of sulfilimines. These gold carbenes undergo C?H insertion, cyclopropanation, and nucleophilic attack to form indoles (44 examples), 3-azabicyclo[3.1.0]hexan-2-imines (24 examples), and imidazoles (3 examples). Our study represents a unique gold-catalyzed reaction between alkynes and sulfur ylides, and also includes the first aza-heterocycle synthesis that proceeds by intermolecular nitrene transfer followed by cyclopropanation of the α-imino gold carbenes. Moreover, an unexpected synthesis of 4-acylquinolines (3 examples) from 2-acylphenyl sulfilimines and propargylic silyl ether derivatives by a 1,2-hydride shift onto the α-imino gold carbene and a subsequent Mukaiyama aldol cyclization was discovered.
- Tian, Xianhai,Song, Lina,Rudolph, Matthias,Rominger, Frank,Oeser, Thomas,Hashmi, A. Stephen K.
-
p. 3589 - 3593
(2019/02/09)
-
- Zn(II)-Catalyzed One-Pot Synthesis of Coumarins from Ynamides and Salicylaldehydes
-
A highly efficient and straightforward synthesis of diversely substituted coumarins from ynamides and salicylaldehydes in the presence of Zn(II) catalyst has been developed. The sulfonamide moiety of ynamides was successfully recycled in this process, serving as an effective traceless directing group for high regioselectivity in the bond-forming event. The advantages of this protocol are good functional group tolerance, broad substrate scope, simple and high-yielding reaction, recovery/reuse of the sulfonamides, low catalyst loading of inexpensive catalyst, and, by these merits, a more cost-effective and greener process.
- Yoo, Huen Ji,Youn, So Won
-
supporting information
p. 3422 - 3426
(2019/05/10)
-
- A Highly Regio- and Stereoselective Syntheses of α-Halo Enamides, Vinyl Thioethers, and Vinyl Ethers with Aqueous Hydrogen Halide in Two-Phase Systems
-
A metal-free regio- and stereoselective method is achieved for the preparation of (E)-configured α-halo enamides, vinyl thioethers, and vinyl ethers using aqueous HX (X = F, Cl, Br, I), which features high functional group compatibility and regio- and stereoselectivity, mild conditions, high efficiency, and rapid transformation. Additionally, the isomers could be yielded readily from the (E)-configured α-halo enamides via photocatalysis or under Sonogashira coupling conditions.
- Cao, Wei,Chen, Ping,Wang, Liang,Wen, Hao,Liu, Yu,Wang, Wanshu,Tang, Yu
-
supporting information
p. 4507 - 4511
(2018/08/09)
-
- Metal-Free [2 + 2 + 2] Cycloaddition of Ynamide-Nitriles with Ynamides: A Highly Regio- and Chemoselective Synthesis of δ-Carboline Derivatives
-
A metal-free formal [2 + 2 + 2] cycloaddition of functionalized ynamide-nitriles with ynamides is disclosed which offers highly efficient access to polysubstituted δ-carboline derivatives under the mediation of TfOH. This strategy is highly regioselective and chemoselective and displays mild conditions, high yields, and efficiency (within 1 min) in addition to substrates scopes (56 examples).
- Wen, Hao,Cao, Wei,Liu, Yu,Wang, Liang,Chen, Ping,Tang, Yu
-
p. 13308 - 13324
(2018/11/02)
-
- Gold-Catalyzed Intermolecular [4+2] Annulation of 2-Ethynylanilines with Ynamides: An Access to Substituted 2-Aminoquinolines
-
A gold-catalyzed intermolecular [4+2] annulation of easily accessible 2-ethynylanilines with ynamides offers a highly region-selective, modular, efficient, and atom-economical strategy for the synthesis of substituted 2-aminoquinolines in up to 93% yield. (Figure presented.).
- Zhao, Ximei,Song, Xinlong,Jin, Hongming,Zeng, Zhongyi,Wang, Qian,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
-
p. 2720 - 2726
(2018/07/29)
-
- α-Imino Gold Carbenes from 1,2,4-Oxadiazoles: Atom-Economical Access to Fully Substituted 4-Aminoimidazoles
-
A novel and atom-economical synthesis of fully substituted 4-aminoimidazoles via gold-catalyzed selective [3 + 2] annulation of 1,2,4-oxadiazoles with ynamides is reported. This protocol represents a new strategy to access α-imino gold carbenes, which corresponds to an unprecedented intermolecular transfer of N-acylimino nitrenes to ynamides. Moreover, the reaction proceeds with 100% atom economy, exhibits good functional group tolerance, and can be conducted in gram scale.
- Zeng, Zhongyi,Jin, Hongming,Xie, Jin,Tian, Bing,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
-
p. 1020 - 1023
(2017/03/15)
-
- Regioselective TfOH-mediated hydroamidation of ynamides with nitriles
-
A new TfOH-mediated reaction of ynamides with nitriles as nucleophiles has been developed. The reaction works efficiently under mild reaction conditions to afford a new class of α-acylaminoenamides readily via the intermediacy of keteniminium ion. The reaction displays generality and a broad substrates scope. Additionally, the α-acylaminoenamides could be transformed to highly substituted pyridine, 4-aminopyrimidine or isoquinoline cores.
- Wang, Wan-Shu,Chen, Ping,Tang, Yu
-
p. 2731 - 2739
(2017/04/14)
-
- Gold-Catalyzed [4+2]- and [3+3]-Annulations of Ynamides with 1-Yn-3-ols to Access Six-Membered Carbocycles and Oxacycles via Three Distinct Cyclizations
-
Three distinct strategies for catalytic annulations between ynamides and 1-yn-3-ols are described; the resulting carbo- and heterocycles were produced efficiently in one-pot operations using a gold catalyst. The chemoselectivities of these annulations are controlled by variations of the substituents of the ynamides and the 1-yn-3-ols. This reaction sequence involves initial alkoxylations of ynamides, followed by Claisen rearrangement of propargylic enol ethers, and ends with 6-endo-trig cyclizations of 1-allenyl-5-amide intermediates. Among these cascade annulations, the cyclizations of 5-allenyl-1-amides to yield 5,6-dihydro-2-pyranones and 6-alkylenecyclohex-2-ene-1-carboxamides are unprecedented in the literature. (Figure presented.).
- Giri, Sovan Sundar,Liu, Rai-Shung
-
p. 3311 - 3318
(2017/09/13)
-
- Borane-catalyzed selective hydrosilylation of internal ynamides leading to β-silyl (Z)-enamides
-
We have developed a borane-catalyzed regioand stereoselective hydrosilylation of internal ynamides for the first time. The scope of ynamide substrates and silane reactants was broad under mild reaction conditions, affording synthetically versatile β-silyl (Z)-enamide products. The observed stereoselectivity was reasoned to be due to the β-silicon effect on a postulated ketene iminium intermediate.
- Kim, Youngchan,Dateer, Ramesh B.,Chang, Sukbok
-
p. 190 - 193
(2017/11/27)
-
- Metal-free, Regio-, and Stereo-Controlled Hydrochlorination and Hydrobromination of Ynones and Ynamides
-
We developed an atom-economical and metal-free method for the regio- and stereo-selective hydrohalogenation of ynones and ynamides using easy to handle DMPU/HX (X = Br or Cl) reagents. The reaction operates under mild conditions and a range of functional groups is well tolerated. We propose that the hydrohalogenation of ynones gives the anti-addition products via a concerted multimolecular AdE3 mechanism and that the hydrohalogenation of ynamides produces the syn-addition products via a cationic keteniminium intermediate.
- Zeng, Xiaojun,Lu, Zhichao,Liu, Shiwen,Hammond, Gerald B.,Xu, Bo
-
p. 13179 - 13187
(2017/12/26)
-
- Ynamides as Racemization-Free Coupling Reagents for Amide and Peptide Synthesis
-
A highly efficient, two-step, one-pot synthetic strategy for amides and peptides was developed by employing ynamides as novel coupling reagents under extremely mild reaction conditions. The ynamides not only are effective for simple amide and dipeptide synthesis but can also be used for peptide segment condensation. Importantly, no racemization was detected during the activation of chiral carboxylic acids. Excellent amidation selectivity toward amino groups in the presence of -OH, -SH, -CONH2, ArNH2, and the NH of indole was observed, making the protection of these functional groups unnecessary in amide and peptide synthesis.
- Hu, Long,Xu, Silin,Zhao, Zhenguang,Yang, Yang,Peng, Zhiyuan,Yang, Ming,Wang, Changliu,Zhao, Junfeng
-
supporting information
p. 13135 - 13138
(2016/10/22)
-
- Gold-catalyzed [3+2]-annulations of α-aryl diazonitriles with ynamides and allenamides to yield 1-amino-1H-indenes
-
Gold-catalyzed [3+2]-annulations of α-aryl diazonitriles with ynamides and allenamides yield 1-amino-1H-indenes in two distinct pathways; the success of these annulations relies on the high electrophilicity of α-cyano arylgold carbenes to activate an ionic pathway.
- Singh, Rahulkumar Rajmani,Pawar, Samir Kundlik,Huang, Min-Jie,Liu, Rai-Shung
-
p. 11434 - 11437
(2016/09/23)
-
- Dioxazoles, a new mild nitrene transfer reagent in gold catalysis: Highly efficient synthesis of functionalized oxazoles
-
A gold-catalyzed regioselective [3+2] cycloaddition of ynamides with 1,4,2-dioxazoles was developed and offers a novel approach to obtain highly functionalized oxazoles under mild reaction conditions. 1,4,2-Dioxazole was found to act as an efficient N-acyl nitrene equivalent to trigger a facile generation of α-imino gold-carbene intermediate through the elimination of a ketone.
- Chen, Ming,Sun, Ning,Chen, Haoyi,Liu, Yuanhong
-
supporting information
p. 6324 - 6327
(2016/05/19)
-
- Synthesis of 2-Aza-1,3-butadienes through Gold-Catalyzed Intermolecular Ynamide Amination/C-H Functionalization
-
A novel gold-catalyzed tandem intermolecular ynamide amination/C-H functionalization has been developed. A variety of highly functionalized 2-aza-1,3-butadienes can be obtained readily by utilizing this strategy. In addition, α-imino gold carbene intermediates are proposed in this amination reaction and with support by DFT (density functional theory) calculations.
- Shu, Chao,Shen, Cang-Hai,Wang, Yong-Heng,Li, Long,Li, Tao,Lu, Xin,Ye, Long-Wu
-
supporting information
p. 4630 - 4633
(2016/09/28)
-
- Diversity in Gold-Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H-Azirines: [3+2] versus [4+3] Cycloadditions
-
Gold-catalyzed cycloadditions of ynamides with azidoalkenes or 2H-azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H-azirine species afford pyrrole products with two regioselectivities when the Cb-substituted 2H-azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron-rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H-benzo[d]azepine products instead.
- Pawar, Samir Kundlik,Sahani, Rajkumar Lalji,Liu, Rai-Shung
-
p. 10843 - 10850
(2015/07/20)
-
- Gold-Catalyzed Intermolecular Nitrene Transfer from 2H-Azirines to Ynamides: A Direct Approach to Polysubstituted Pyrroles
-
(Chemical Equation Presented). An effective gold-catalyzed intermolecular nitrene transfer by the reaction of 2H-azirines and ynamides is reported, which provides highly substituted pyrroles in a straightforward manner. This transformation proceeds under mild conditions and gives the polysubstituted pyrroles in good-to-excellent yields. Preliminary results indicate that a nongold carbenoid pathway is preferred for current pyrrole synthesis.
- Zhu, Lei,Yu, Yinghua,Mao, Zhifeng,Huang, Xueliang
-
-
- A gold-catalysed fully intermolecular oxidation and sulfur-ylide formation sequence on ynamides
-
An efficient C-O, C-S and C-C bond-forming sequence leads to functionalised compounds bearing sulfur-substituted quaternary carbons. Ynamides are employed as diazo-equivalents to access the [2,3]-sigmatropic rearrangements of allyl sulfonium ylides by a t
- Santos, Micka?l Dos,Davies, Paul W.
-
supporting information
p. 6001 - 6004
(2014/05/20)
-
- Regiocontrolled gold-catalyzed [2+2+2] cycloadditions of ynamides with two discrete nitriles to construct 4-aminopyrimidine cores
-
Reported herein is the novel gold-catalyzed intermolecular [2+2+2] cycloaddition of ynamides with two discrete nitriles to form monomeric 4-aminopyrimidines, which are pharmaceutically important structural motifs. The utility of this new cycloaddition is demonstrated by the excellent regioselectivity obtained using a variety of ynamides and nitriles.
- Karad, Somnath Narayan,Liu, Rai-Shung
-
p. 9072 - 9076
(2014/11/07)
-
- A direct route into fused imidazo-diazines and imidazo-pyridines using nucleophilic nitrenoids in a gold-catalyzed formal [3 + 2]-dipolar cycloaddition
-
Pyridinium N-(heteroaryl)aminides can be employed as robust and practical synthetic equivalents of nucleophilic 1,3-N,N-dipoles in a formal cycloaddition onto electron-rich alkynes under gold catalysis. Convergent and regioselective access to five types of imidazofused heteroaromatics is provided from the appropriate aminide. The efficient transformation accommodates significant structural variation around the aminide, ynamide, or indolyl-alkyne reactants and tolerates sensitive functional groups.
- Garzon, Miguel,Davies, Paul W.
-
supporting information
p. 4850 - 4853
(2015/04/27)
-
- Gold-catalyzed intermolecular [4+2] and [2+2+2] cycloadditions of ynamides with alkenes
-
As good as gold: Gold-catalyzed intermolecular [4+2] cycloadditions of 2-arylynamides with alkenes and gold-catalyzed [2+2+2] cycloadditions of terminal ynamides with enol ethers have been developed (see scheme). The [4+2] cycloaddition is compatible with a range of alkenes and arylynamides and the [2+2+2] cycloaddition can also accommodate a variety of different arylynamide and enol ether substrates.
- Dateer, Ramesh B.,Shaibu, Balagopal S.,Liu, Rai-Shung
-
supporting information; experimental part
p. 113 - 117
(2012/02/16)
-
- Gold-catalyzed 1,2-difunctionalizations of aminoalkynes using only N- and O-containing oxidants
-
We report two viable routes for the 1,2-difunctionalization of aminoalkynes using only oxidants. In the presence of a gold catalyst, nitrones enable the oxoamination of aminoalkynes 1 to form 2-aminoamides 2. With a suitable gold catalyst, nitrosobenzenes implement an alkyne/nitroso metathesis of the same substrates to give 2-oxoiminylamides 3. These two novel oxidations also provide 1,2-aminoalcohols with opposite regioselectivity via NaBH4 reduction in situ.
- Mukherjee, Anupam,Dateer, Ramesh B.,Chaudhuri, Rupsha,Bhunia, Sabyasachi,Karad, Somnath Narayan,Liu, Rai-Shung
-
supporting information; experimental part
p. 15372 - 15375
(2011/11/07)
-
- Enantioselective ficini reaction: Ruthenium/PNNP-catalyzed [2+2] cycloaddition of ynamides with cyclic enones
-
(Chemical Equation Presented) Chiral cyclobuteneamides made easy: Double chloride abstraction from the ruthenium/PNNP complex 1 in the presence of unsaturated β-keto esters 2 gives the dicationic adducts [Ru(2)(PNNP)] 2+ (3) that catalyze the [2+2] cycloaddition of a variety of ynamides 4 to produce cyclo-buteneamides 5 with high yield and enantioselectivity (see scheme).
- Schotes, Christoph,Mezzetti, Antonio
-
supporting information; experimental part
p. 3072 - 3074
(2011/04/24)
-