Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• Ruichen Lan Brock Yager Yoonsun Jee Cynthia S. Day Amanda C. Jones Chemistry, Wake Forest University, 1834 Gulley Rd., Winston-Salem, NC, 27109, USA 10.3762/bjoc.20.43 Abstract Kinetic studies on the intramolecular hydroamination of protected variants of 2,2-diphenylpent-4-en-1-amine were carried

• both within the context of a classic gold π-activation/protodeauration mechanism and a general acid-catalyzed mechanism without intermediate gold alkyls. Keywords: alkene hydroamination; general acid catalysis; gold catalysis; isotope effect; phosphine ligand effect; solvent effect; Introduction

• ) protodeauration (Scheme 1), the depth of experimental mechanistic validation achieved for allenes and alkynes have not been reproduced with alkenes. In an important foundational study by Toste, the expected alkylgold intermediate from intramolecular alkene hydroamination was isolated, however, turnover

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• hydroamination reaction products via a proton-coupled electron transfer (PCET) mechanism. Cyclic voltammetry (CV) analysis indicated that the chemoselectivity was derived from the size of the hydrogen bond complex, which consisted of the carbamate substrate and phosphate base, and could be controlled using

• 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as an additive. These results provide fundamental insights for the design of PCET-based redox reaction systems under electrochemical conditions. Keywords: amidyl radical; cyclic voltammetry; electrosynthesis; hydroamination; proton coupled electron transfer

• electron-transfer to give the corresponding radical species through oxidative X–H bond cleavage. One such species is the amidyl radical, which is broadly synthetically useful as a nitrogen source in hydroamination reactions and as a hydrogen atom transfer (HAT) reagent for remote C–H activation [2][3][4][5

Friedel–Crafts acylation of benzene derivatives in tunable aryl alkyl ionic liquids (TAAILs)

• Swantje Lerch,
• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2023, 19, 212–216, doi:10.3762/bjoc.19.20

• proved to be a potent reaction medium in catalytic hydrosilylation [53], hydroamination and hydroarylation [54], as well as for the synthesis of nanoparticles [55][56]. Results and Discussion Ionic liquids 1–6 were synthesized via a three-step procedure starting from commercially available aniline

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• absence of organic halide, the copper salts catalyzed the hydroamination of the alkene [59]. Mechanistic studies showed that the copper–amido complex coordinated with alkenes, which then acted as a primary photocatalyst. After light irradiation, the excited alkene–copper–amido species offered a benzyl

• radical and the organocopper via SET with hydrogen atom abstraction from CH3CN. Subsequently, the benzyl radical was captured by the organocopper to generate the hydroamination products (Scheme 10). In 2020, the same group [60] reported the copper-catalyzed asymmetric dual carbofunctionalization of

• -base photocatalysis. Olefinic C–H functionalization and allylic alkylation. Cross-coupling of unactivated alkenes and CF3SO2Cl. Chlorosulfonylation/cyanofluoroalkylation of alkenes. Hydroamination of alkenes. Cross-coupling reaction of alkenes, alkyl halides with nucleophiles. Cross-coupling of alkenes

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• tandem reaction of 2-trifluoromethyl-1,3-enynes 36 with primary amines, affording various trifluoromethyl-substituted 3-pyrrolines [56]. Subsequently, they also developed a novel route for the synthesis of halogenated trifluoromethylated pyrroles 37 and 38 by sequential intermolecular hydroamination

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• intramolecular hydroamination in the presence of base. Conclusion In conclusion, we have reported on the chelation-assisted oxidative copper-promoted cascade C−H alkynylation and intramolecular annulation. The removable N-2-pyridylhydrazide was utilized to facilitate copper(II)-promoted C−H activations. Thus

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• activate unsaturated bonds, and examples of olefin hydroalkylation, hydroarylation, hydrofluorination, hydroamination, and aminoheteroarylation, among others, can be found in the literature [36][37]. The first example of an olefin hydroalkylation promoted by gold catalysis appeared in 2004 in the work by

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• previously described approach for iminyl radical formations was employed [140]. The same tunable aryloximes 31.1 were used as electrophores to generate the desired amidyl radicals. This methodology allowed the development of a hydroamination/cyclization cascade to give the heterocycles 31.2 and

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• were utilized for the current reaction. The results exhibited that the use of 5-methylisoxazol-3-amine (7) gave a complex mixture. In contrast, 3-methylisoxazol-5-amine (8a) led to the formation of the desired pyrrole 10aa in 99% yield. Notably, the hydroamination product cannot be found in the

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• propargylureas (leading to 2-imidazolones) and extend the range of Lewis acid-catalyzed azole syntheses based on N-carbonyl propargylamines. Keywords: alkyne hydroamination; cyclocondensation; Lewis acid catalysis; multicomponent reactions; propargylurea; Introduction The pioneering publications of Beller and

• the mechanistic prospective, the reaction probably proceeds via Zn(OTf)2-catalyzed alkyne hydroamination followed by cyclodehydration as depicted in Figure 3, in full analogy with the previously proposed mechanism [2][3]. Conclusion In summary, we have successfully employed propargylureas in the

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• (diols). Seleno-Pummerer reactions of 3-selanylmethylpyrroles also proceeded via in situ generation of selenoxides, followed by a treatment with TBAH. Keywords: hydroamination; Pummerer reaction; pyrrole; pyrroloazepine; 1,7-sulfur shift; Introduction Pyrrolo- and indoloazepine skeletons are chemical

• -carboxamides that produces pyrrolo[2,3-c]- and [2,3-d]azepinones [30][31]. However, this reaction is not suitable for the synthesis of pyrrolo[3,2-c]azepines in viewpoint of the difficulties in preparing the starting materials. We previously reported that the hydroamination/cyclisation reaction of sulfanyl-1,6

• -bromobenzenesulfonyl derivative, which was expected to act as a good substrate for the isolation of crystals, and performed the same sequential process of sulfanyl-1,6-diynes to the oxazine derivatives (Scheme 7). Hydroamination–cyclisation of diyne 1 with N-allyl-p-bromobenzenesulfonamide 3g and the successive

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• = R3, R2 = H) were obtained by cyclization of the corresponding o-(o-aminophenylethynyl)anilines 15a–c with PdCl2(MeCN)2 [29][30]. Indoles 14d,e (R1 ≠ R3) could not be obtained in such way (due to the lack of selectivity between the two different NH2 groups in the hydroamination reaction), and were

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• single-electron transfer (SET) between CF3SO2Cl and the association CuBr/chiral phosphoric acid. In the process, SO2 and HCl were released, but the latter was scavenged by Ag2CO3, minimising its impact on the reaction process by notably avoiding hydroamination side reactions. The trifluoromethyl radical

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• –enantioselective protonation using α,β-unsaturated nitriles has remained unexplored for substrates other than methacrylonitrile. The Togni lab has explored using ferrocenyl tridentate nickel(II) and palladium(II) complexes as chiral Lewis acid catalysts for the hydrophosphination and hydroamination of

• methacrylonitrile (Figure 4) [70][71][72][73][74]. Other researchers have reported platinum [75], nickel [76], and zirconium [77] catalysts for the hydrophosphination and hydroamination of methacrylonitrile; however, these examples provided product with significantly lower enantioselectivity. In 2004, the Togni lab

• and co-workers subsequently reported the hydroamination of methacrylonitrile 174 using palladium(II) catalyst 172 (Scheme 42a) [72]. Low temperature and bulky aryl groups on the catalyst were necessary to achieve good levels of enantioselectivity. In a later study, their nickel(II) catalyst 171 proved

Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• containing an enamine-cobalticenium group (16) was first prepared by hydroamination of the ethynyl cobalticenium with n-butylamine-substituted norbornene 15. Next, 16 was polymerized to 17, by ROMP under mild conditions (Scheme 7A). In the second approach, first, the monomer 14 was polymerized to 17a

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• Road, Shengyang 110016, P. R. China 10.3762/bjoc.11.47 Abstract We report a synthetic methodology for the construction of the fused heterocyclic compounds pyrido[2,1-b]quinazolin-9(1H)-ones and pyrrolo[2,1-b]quinazolin-9(1H)-ones through an AgOTf-catalyzed intramolecular alkyne hydroamination reaction

• . The methodology is applicable to a wide scope of substrates and produces a series of fused quinazolinone heterocycles in good to excellent yields. Keywords: heterocyclic molecules; intramolecular alkyne hydroamination; silver; Introduction Quinazolinone is a core skeleton for naturally existing

• dangerous substrates bearing an azide group, and require a high reaction temperature and a long reaction time [2][10]. Recently, transition metal catalyzed hydroamination of alkynes [14][15][16][17][18][19][20][21][22][23][24][25][26], alkenes [15][27][28][29][30][31] and dienes [32][33] has been widely

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• stereoselective preparation of such amines. Throughout the last decades, several strategies [3] such as stereospecific amination via C–H insertion [5][6][7][8] or asymmetric olefin hydroamination [9][10][11][12][13] have been investigated in order to obtain access to optically pure amines. However, the major

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• hydroamination/glycosylation on glycal scaffolds has been developed to form propargyl 3-tosylamino-2,3-dideoxysugars in a one-pot manner. Subsequent construction of multivalent 3-tosylamino-2,3-dideoxyneoglycoconjugates with potential biochemical applications was presented herein involving click conjugations as

• few examples of oligosaccharides and glycopeptides mimics have so far been prepared by a click chemistry strategy [40][41][42][43][44][45][46][47][48]. Most recently, we developed a strategy for the synthesis of 3-amino-2,3-dideoxysugars using a regio- and stereoselective tandem hydroamination

• -allohexopyranoside (2a) in gram scale via BF3∙OEt2-promoted one-pot three-component α-selective tandem hydroamination/glycosylation reaction (Scheme 1). In fact, when 3,4,6-tri-O-acetyl-D-glucal (1a), propargyl alcohol and p-toluenesulfonamide were subjected to a one-pot reaction in the presence of 2.2 equiv of BF3

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers

• Samir Kundu,
• Babli Roy and
• Basudeb Basu

Beilstein J. Org. Chem. 2014, 10, 26–33, doi:10.3762/bjoc.10.5

• and also as spacers in metal-organic frameworks [9][10][11][12][13][14]. For example, vicinal dithioether-based zirconium and titanium complexes have been used for alkene polymerization and hydroamination [15][16][17][18]. Chiral dithioethers have been prepared and their iridium complexes have been

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• activated carbonyl compound 9 was also hypothesized (Scheme 4b). 3 Hydroamination of olefins 3.1 Mechanistic considerations Due to the ubiquity of the C–N bond in organic compounds the development of efficient catalytic systems for the hydroamination of olefins is of particular significance from a practical

• hydroamination of alkenes. Detailed computational studies on the addition of benzyl carbamate to dienes revealed the protodeauration as the rate-determining step of the reaction [34]. Mechanistically, the initial stage was determined dealing with the energetically favourable substitution of the TfO− ligand from

• type 11 were isolated by Toste in the intramolecular hydroamination of alkenyl urea 14 with a stoichiometric amount of phosphine–gold complex [(PPh3Au)3O]BF4 (Scheme 5a) [2]. The reaction proceeded at room temperature and was found being favoured by electron-withdrawing ligands. Finally, the use of the

Synthesis of axially chiral gold complexes and their applications in asymmetric catalyses

• Yin-wei Sun,
• Qin Xu and
• Min Shi

Beilstein J. Org. Chem. 2013, 9, 2224–2232, doi:10.3762/bjoc.9.261

• axially chiral binaphthyl moiety derived from the hindered rotation around C–C and C–N bonds. In the asymmetric intramolecular hydroamination reaction most of these chiral Au(I) complexes showed good catalytic activities towards olefins tethered with a NHTs functional group to give the corresponding

• PhMgBr. Its structure was also confirmed by the X-ray crystal structure diffraction (Figure SI-1 in Supporting Information File 1). The catalytic activities of these gold complexes were examined by the gold-catalyzed asymmetric intramolecular hydroamination of olefin 24 tethered with a NHTs functional

• group. Intramolecular hydroamination reaction catalyzed by Au(I) complexes. We synthesized a variety of Au complexes both neutral and cationic and subsequently used these complexes as catalysts in a variety of reactions. High enantioselectivities were achieved in the asymmetric intramolecular

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• , nitrogen C–H insertion [10][11][12], hydroamination [13][14][15][16], hydroaminoalkylation [17][18], reductive amination [19][20][21][22][23], and enamine reduction [23][24][25][26][27] are experiencing a renaissance; while imine reduction [23][28][29][30], N-acylenamide reduction [23][24], and carbanion