Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

• Jiahuan Peng and
• Da-Ming Du

Beilstein J. Org. Chem. 2013, 9, 1210–1216, doi:10.3762/bjoc.9.137

• stereogenic centers [1][2][3][4][5][6][7][8][9][10][11][12][13]. Newly developed tandem/domino reactions are increasingly applied in the synthesis of natural products and other biologically active compounds [14][15][16]. Dihydrocoumarins, chromans, and chromenes can be found in many natural products and

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• of a wide variety of heterocycles and pharmaceutical compounds [6][7][8][9][10][11]. Many domino reactions have been developed by trapping this kind of β-enamino ester with sequential adding of nucleophilic or electrophilic reagents to give versatile nitrogen-containing compounds and N,O-heterocycles

• [12][13][14][15][16][17][18][19][20][21][22][23]. Recently, Perumal and we have both developed an efficient synthetic procedure for functionalized spiro[indoline-3,4’-pyridines] by domino reactions of in situ generated β-enamino esters, isatin and malononitrile with triethylamine as the base catalyst

• [24][25]. A literature survey indicated that there has been an explosion of activity around the synthesis of spirooxindoles in the past years [26][27][28][29][30][31]. Encouraged by these results, and hunting for new synthetic methods for functionalized spirooxindoles, we investigated the domino

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• Domingos and co-workers in a PM3 study on domino reactions with nitroalkenes [34]. Additionally, it is possible that the high internal pressure of the solvent acts synergistically to promote the enhancement of the reaction rate of 5a–c and should not be neglected. In all cycloadditions, independent of the

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• intricate carbon frameworks. In this context, reactions allowing the concomitant or sequential formation of multiple new bonds acquire a special importance [1]. Radicals, in particular, have proved to be especially apt for such a task, and numerous cascade or domino sequences have been described over the

• extra equivalent of tributylstannane ensures its in situ reductive removal. This domino radical cyclisation represents, in fact, a general strategy for the construction of indolizidines and pyrrolizidines, which constitute the core structure of numerous alkaloids. For pyrrolizidines, one needs simply to

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• Abstract A microwave-assisted three-component protocol involving N-1 alkylation of 2-alkynylindoles with epichlorohydrin, ring opening of the epoxide with sodium azide, and an intramolecular Huisgen azide–internal alkyne 1,3-dipolar cycloaddition domino sequence has been described. The efficacy of the

• methodology has been demonstrated by treating various 2-alkynylindoles (aromatic/aliphatic) with epichlorohydrin and sodium azide furnishing annulated tetracyclic indolodiazepinotriazoles in satisfactory yields. Keywords: 2-alkynylindoles; azides; 1,3-dipolar cycloaddition; domino reaction

• application in a three-component domino format are scarce [29][30]. In our laboratory, we had been employing functionalized indoles for the synthesis of annulated indole-based polyheterocycles either in a multicomponent or in a one-pot format [31][32][33][34][35]. In this continuation, we next directed our

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• 60. However, the reaction suffered from very poor yields (15–21%). The reaction is thought to proceed through the condensation of aldehyde 60 and prolinol 61 to give a chiral iminium-ion intermediate. This intermediate then undergoes a domino reaction involving a Michael reaction with salicylaldehyde

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

• Jing Sun,
• Hong Gao,
• Qun Wu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2012, 8, 1839–1843, doi:10.3762/bjoc.8.211

• Jing Sun Hong Gao Qun Wu Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.8.211 Abstract In the presence of p-toluenesulfonic acid as catalyst the domino reaction of arylamines, methyl propiolates and aromatic aldehydes in ethanol

• proceeded smoothly to give polysubstituted 1,2,3,4-tetrahydroquinolines in moderate yields. The reaction is believed to involve the Povarov reaction of in situ generated β-enamino ester with the in situ formed aromatic imine. Keywords: β-enamino ester; domino reaction; electron-deficient alkyne; Povarov

• reaction; tetrahydroquinoline; Introduction The Diels–Alder reaction is recognized as a powerful reaction in synthetic strategies for the production of natural and unnatural polycarbocycles and polyheterocycles [1][2][3]. Therefore, the hetero-Diels–Alder reactions and domino reaction procedures have been

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• protecting-group chemistry [11][12][13][14][15][16]. Moreover, palladium-catalyzed reactions involving ethylenic double bonds can also lead to domino processes such as carboaminations [17][18][19], diaminations [20][21], aminooxygenations [22][23], and aminohalogenations [24][25]. The most common reactions

• domino processes. Review Intermolecular reactions involving alkenes Alkenylation reactions of indoles run through a key C–H activation step involving an electrophilic palladation and an electron-deficient Pd(II) catalyst. The mechanism of these reactions involves the generation of a σ-alkyl complex I

• -benzoylindole 44 occurred in the cyclization providing the tetracyclic compound 45 (Scheme 22). The presence of an electron-donating group on the linked arene was proven to be essential for obtaining the product in high yield. Alkenylation reactions involving domino processes In 2004, Widenhoefer described the

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• 65880378 10.3762/bjoc.8.195 Abstract The catalytic synthesis of nitrogen-containing heterocycles is of great importance to medicinal and synthetic chemists, and also a challenge for modern chemical methodology. In this paper, we report the synthesis of pyrazolidine derivatives through a domino aza-Michael

• good results (up to 86% yield, >10/1 regioselectivity, >20:1 dr, 99% ee) in the presence of (S)-diphenylprolinol trimethylsilyl ether catalyst. Keywords: aza-Michael; domino; hydrazine; organocatalysis; pyrazolidine; Introduction Pyrazolidines are privileged and valuable heterocyclic compounds, which

• , organocatalytic domino/cascade reactions have come into focus and become a powerful synthetic approach that allows the construction of structurally diverse and complex molecules, minimizes the number of manual operations, and saves time, effort, and production costs [45][46][47]. Thus, many nitrogen-containing

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• six membered mono hetero-atom containing, biologically active heterocycles, such as functionalized chromenes (benzopyranes), thiochromenes (thiobenzopyranes) and 1,2-dihydroquinolines, by means of tandem/domino hetero Michael addition reactions, or modified versions [33][34][35][36][37][38], covering

• high yield (up to 90%) and enantioselectivity (up to 99%), whereas compound 2 having electron-withdrawing groups provided poor results. Very recently, Xu et al. [46] reported an improved protocol for the domino-oxa-Michael reaction of salicylaldehydes 1 with α,β-unsaturated aldehydes 2 employing

• -unsaturated ketones have also responded as Michael acceptors in the organocatalytic tandem Michael addition reaction towards the synthesis of tetrahydroxanthones. Córdova et al. [50], in 2007, reported the first organocatalytic asymmetric synthesis of tetrahydroxanthenones through the domino Michael–aldol

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

• Stefan Bräse,
• Nicole Volz,
• Franziska Gläser and
• Martin Nieger

Beilstein J. Org. Chem. 2012, 8, 1385–1392, doi:10.3762/bjoc.8.160

• , Germany Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, FIN-00014 Helsinki, Finland 10.3762/bjoc.8.160 Abstract After prosperous domino reactions towards benzopyrans, the products were used as the starting material in Lewis acid catalyzed and

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• further manipulations on the alkynyl residue. Our previous studies also revealed that even carbohydrate-derived alkynes can be utilized under these reaction conditions in an efficient manner [23]. Our recent interest in domino reactions starting with 2-brominated glycals [26][27][28] motivated us to

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• different approach to α,β-alkynyl ketone derivatives as pyrazole precursors. They established a four-component domino process combining various organic halides, terminal alkynes, hydrazines, and carbon monoxide at room temperature. In this case, all components are mixed at the very beginning of the process

One-pot Diels–Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework

• Boubacar Sow,
• Gabriel Bellavance,
• Francis Barabé and
• Louis Barriault

Beilstein J. Org. Chem. 2011, 7, 1007–1013, doi:10.3762/bjoc.7.114

• ) are underway and will be reported in due course. Structures of naturally occurring PPAPs. Gold(I)-catalyzed 6-endo-dig cyclization. Synthesis of papuaforin A core 4. Proposed domino Diels–Alder reaction/gold(I)-catalyzed cyclization. One-pot Diels–Alder cycloaddition/gold(I) catalyzed carbocyclization

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• -arylhydroxylamines with 1,3-dicarbonyl compounds in situ) to give 3-carbonylated benzofuran derivatives 300 [153]. Trisubstituted isoxazoles 303 were obtained from alkynyl oxime ether 301 through a gold-catalyzed domino reaction involving cyclization and subsequent Claisen-type rearrangement [154]. The presence of

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

• Olivier Debleds,
• Eric Gayon,
• Emmanuel Vrancken and
• Jean-Marc Campagne

Beilstein J. Org. Chem. 2011, 7, 866–877, doi:10.3762/bjoc.7.99

• allowing the activation of both alcohols and π-bonds. We therefore assumed that we could take advantage of this ambivalence in order to perform new domino processes [44][45]. Moreover, due to these ambivalent properties, the control of the chemo- and regioselectivity is challenging and raises interesting

• domino reactions. Review Gold-catalyzed alcohol substitution Scope and limitations In the past few years, homogeneous gold catalysis has emerged as an efficient tool to activate triple bonds for the addition of various nucleophiles to alkynes. We initially anticipated that, through coordination to π-bond

• might be expected under gold catalysis conditions. For example, it could be interesting to combine both Lewis and π-acidities to promote domino reactions [44][45]. Domino reactions in the presence of bi-nucleophiles We anticipated that by using bi-nucleophiles HNu1–Nu2H, the first nucleophilic

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• domino processes, for which gold pre-catalysts were found to be outstandingly effective, were paralleled by employing iodine electrophiles in place of gold compounds. This review highlights how, in certain cases, iodonium activation can match gold-catalyzed reactions to construct identical product

• scaffolds. Likewise, processes are discussed where mostly identical starting materials are transformed into diverse frameworks depending on whether gold or iodonium activation was used to trigger the reaction. Keywords: catalysis; cycloisomerizations; domino reactions; gold; iodine; Introduction Over the

• past decade, the diverse reactivity of carbophilic Lewis acids has attracted considerable interest in the development of domino reactions [1][2][3][4][5] that are initiated by the catalytic activation of π-systems [6][7][8][9][10][11][12][13]. In particular, the utilization of gold pre-catalysts has

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• transformation has been achieved in two separate steps, with isolation and purification of the 3-unsubstituted indole intermediate. Domino or one-pot processes constitute a more efficient access to organic molecules, as they avoid the use of time and resource consuming work-up, and purification procedures [5][6

• ][7]. When considering the importance of multi-functionalized indoles, it is therefore not surprising that the aniline cyclization–electrophilic substitution sequence has been achieved by means of several metal-catalyzed domino processes (Scheme 1) [8][9][10]. Among the different π-activating metals

• capable of promoting nucleophilic attack on acetylenes, gold has recently attracted interest from the synthetic chemistry community [11][12][13][14]. Gold catalysts have also been used in domino sequences starting from o-alkynylanilines. Arcadi and Marinelli reported that gold-catalyzed cyclization of 2

Rh-Catalyzed rearrangement of vinylcyclopropane to 1,3-diene units attached to N-heterocycles

• Franca M. Cordero,
• Carolina Vurchio,
• Stefano Cicchi,
• Armin de Meijere and
• Alberto Brandi

Beilstein J. Org. Chem. 2011, 7, 298–303, doi:10.3762/bjoc.7.39

• domino 1,3-dipolar cycloaddition/thermal rearrangement sequence, were converted by Wittig methylenation to the corresponding vinylcyclopropanes (VCPs), which underwent rearrangement to 1,3-dienes in the presence of the Wilkinson Rh(I) complex under microwave heating. The previously unexplored Rh(I

• shift in the cyclopropanated 1,6-diradical intermediate, which in this case is probably facilitated by the enhanced mobility of the benzylic hydrogen and by the formation of the conjugationally stabilized imine 9 [11]. The 1,3-dipolar cycloaddition/thermal rearrangement domino reaction of BCP (2) with

Photoinduced homolytic C–H activation in N-(4-homoadamantyl)phthalimide

• Nikola Cindro,
• Margareta Horvat,
• Kata Mlinarić-Majerski,
• Axel G. Griesbeck and
• Nikola Basarić

Beilstein J. Org. Chem. 2011, 7, 270–277, doi:10.3762/bjoc.7.36

• compounds [49], we turned our attention to adamantylphthalimides [50][51][52]. Recently, in cooperation with the group of Griesbeck we discovered a photoinduced domino reaction of adamantylphthalimide that involves two consecutive γ H-abstractions and leads to a complex methanoadamantane benzazepinone 2

• (Scheme 1) [51]. The mechanism of the photoinduced domino reaction was investigated and it was found that it probably takes place from a higher excited triplet state or the singlet state [52]. Herein, we report the synthesis and photochemistry of a phthalimide derivative of homoadamantane 5. The research

• optimization was performed by use of DFT B3LYP/6-31G. Photoinduced domino reaction of adamantylphthalimide. Synthesis of homoadamantylphthalimide 5. Products after irradiation of 5. Proposed mechanism for the photochemical transformation of 5. Supporting Information Supporting Information File 48: Supporting

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• two triquinacene units could be coupled (Scheme 8). The requisite C10H10 moiety, 44, has been prepared (most elegantly via Paquette’s domino Diels–Alder route [26]) but all attempts at controlled dimerization (even on a transition metal template [27]) have so far proven fruitless. A second approach is

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• series of aryl halides, aryl iodides 63 were the most active. The presence of air and water gave only slightly lower yields. Other heteroarylamines also gave good yields [39]. The copper-catalysed domino-indole synthesis facilitated access to new Chek1/KDR kinase inhibitors 67 from

Total synthesis of (±)-coerulescine and (±)-horsfiline

• Mukund G. Kulkarni,
• Attrimuni P. Dhondge,
• Sanjay W. Chavhan,
• Ajit S. Borhade,
• Yunnus B. Shaikh,
• Deekshaputra R. Birhade,
• Mayur P. Desai and
• Nagorao R. Dhatrak

Beilstein J. Org. Chem. 2010, 6, 876–879, doi:10.3762/bjoc.6.103

• radical cyclizations [20][21][22][23][24], electrophilic cyclization [25], asymmetric nitroolefination reaction [26], palladium asymmetric allylic alkylation [27], palladium-catalyzed domino Heck–cyanation [28], Pd-catalyzed intramolecular cyanoamidation [29][30], NHC-mediated O- to C-carboxyl transfer

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• , only highly reactive ferrocenyl alcohols 29a or benzhydrols 29b–d, which result in highly stabilized carbocations upon elimination, can be used in this procedure (Scheme 13) [50]. An interesting domino reduction–alkylation procedure was recently developed by Peris et al. employing a versatile Ir-Cp

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• ) [114]. 5.4. Parson. Radical cyclization The development of novel cascade (or domino) radical reactions is an active area of current research, and one approach to the mitomycin ring system focused on the application of 1-6-hydrogen atom transfer to create a pyrrolidinone radical, which could then