Tetrahedron 72 (2016) 5257e5283

Contents lists available at ScienceDirect

Tetrahedron

journal homepage: www.elsevier.com/locate/tet

Tetrahedron report 1120 Advances of azide-alkyne cycloaddition-click chemistry over the recent decade

Maya Shankar Singh *, Sushobhan Chowdhury, Suvajit Koley

Department of Chemistry (Centre of Advanced Study), Institute of Science, Banaras Hindu University, Varanasi 221005, India article info

Article history: Received 5 September 2015 Available online 14 July 2016

Keywords: Azide-alkyne Click chemistry CuAAC 1,2,3-Triazoles Copper catalysis Organic synthesis

Contents

1. Introduction ...... 5257 2. Mechanistic overview ...... 5258 3. Copper-catalyzed reactions ...... 5258 3.1. Copper halide catalysis ...... 5259 3.2. Copper sulfate catalysis ...... 5264 3.3. Copper acetate catalysis ...... 5268 3.4. Copper triflate catalysis ...... 5270 3.5. Use of other copper catalysts ...... 5271 4. Use of other non-copper catalysts ...... 5274 5. Photoclick chemistry ...... 5277 6. Advances of click methods in chemical biology ...... 5279 7. Summary and outlook ...... 5280 Acknowledgements ...... 5280 References and notes ...... 5280 Biographical sketch ...... 5283

1. Introduction the tools of their arsenal to improve the ease and practicality of synthesis and related separation/purification processes. Huisgen During the past years, a variety of scientific and methodological 1,3-dipolar cycloaddition between organic azides and alkynes is developments have been achieved, which urge chemists to increase one among many synthetic tools that became quite well-known over the recent decade, mainly due to its key improvement in terms of rate and regioselectivity. The revolutionary idea was in- dependently introduced by Sharpless and Meldal groups in 2002 * Corresponding author. Fax: þ 91 542 236 8127; e-mail address: mayashankarbhu@ through the introduction of Cu(I) catalysis termed as ‛Click gmail.com (M.S. Singh). http://dx.doi.org/10.1016/j.tet.2016.07.044 0040-4020/Ó 2016 Elsevier Ltd. All rights reserved. 5258 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

Chemistry’.1 Copper-catalyzed azide-alkyne cycloaddition (CuAAC) undergoes ring contraction to give copper triazolyl derivative, is a type of Huisgen 1,3-dipolar cycloaddition based on the for- which upon protonolysis gives the desired 1,2,3-triazole product mation of 1,4-disubstituted 1,2,3-triazoles between a terminal al- (Fig. 1). kyne and an aliphatic azide in the presence of copper, and is classified as a ‛click reaction’. Click chemistry promotes the use of organic reactions that allow the connection of two molecular building blocks in a facile, selective, high-yielding reaction under mild reaction conditions with few or no byproducts. Furthermore, this chemistry has the capacity to promote bioconjugation and peptide ligation, stemming from the properties of the triazole linkage as a peptide mimetic. The tremendous synthetic potential of initial protocols for Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes was limited by the markable disadvantages like heat- ing requirement, prolonged reaction time and formation of struc- tural isomers due to the lack of selectivity. The wonderful Cu(I)- catalyzed modification introduced at the dawn of last decade, allowed the cycloaddition to occur at room temperature or with moderate heating leading to the exclusive formation of 1,4- disubstituted triazole with shortest workup and purification steps. In 2005, another analogous RuAAC was reported by Fokin group, which led to the selective formation of 1,5-disubstituted triazole.2 Therefore, these remarkable modifications turned azide- alkyne click method a practically quantitative, robust, insensitive Fig. 1. Proposed mechanism for copper-catalyzed azide-alkyne cycloaddition (CuAAC). and general orthogonal ligation reaction that is suitable in all as- pects of drug discovery, combinatorial chemistry, target-templated The analogous RuAAC does not involve a ruthenium acetylide in situ chemistry, material chemistry, proteomics and DNA research intermediate like copper, since it applies to both terminal as well as using bio-conjugation reactions.1 non-terminal alkynes. In the first step, the spectator ligands get Since the introduction of Cu(I) catalysis, azide-dipolarophile 1,3- displaced to form activated complex. This is followed by oxidative dipolar cycloaddition has been advanced remarkably over the last coupling between terminal nitrogen of azide and more electro- decade, and now has engulfed almost every section of chemistry negative less sterically demanding carbon of the alkyne to form and applied sciences. Realizing the importance and practical ap- a Ruthenacycle. The Ruthenacycle then undergoes reductive elim- plicability of the method, a number of reviews describing its vari- ination to release 1,2,3-triazole compound regenerating the active ous aspects in different scientific fields like carbohydrate chemistry, complex for the next cycle (Fig. 2).6 polymer, drug discovery, materials etc. are already reported and emerging frequently in the literature.3 However, no well-directed database describing the azide-dipolarophile cycloaddition meth- odologies developed over the recent years is yet reported. There- fore, this is a significant topic for all the sectors of chemistry and applied sciences. To fulfill the demand and in continuation of our previous report on 1,3-dipolar cycloaddition chemistry,4 herein we present an overview of the open literature focussed on the de- velopment of azide-dipolarophile 1,3-dipolar cycloaddition chem- istry over the recent years (2006 onwards). Starting with a preliminary discussion on the mechanistic aspects, the report is categorized based on different dipolarophiles to couple with azide dipole leading to the formation of diverse 1,2,3-triazoles and re- lated systems. The azide-alkyne cycloaddition section is further sub-categorized based on the use of different copper catalysts (i.e., click chemistry) as well as non-copper catalysts. Additionally, a sub-section based upon the short discussion on photoclick chemistry under click methods on chemical biology has also been included. In this review, we use the terms CuAAC and click chem- Fig. 2. Proposed mechanism for ruthenium catalyzed azide-alkyne cycloaddition istry interchangeably. (RuAAC).

2. Mechanistic overview

The classical Huisgen 1,3-dipolar cycloaddition of organic azide 3. Copper-catalyzed reactions with dipolarophiles is a one-step process,4 whereas its copper(I)- catalyzed variant is considered to be a step-wise process in- The copper either as metal or in salt form (ionic or complex) has volving copper in the intermediate steps.5 In the initial step, copper been employed as a most effective catalyst to promote the 1,3- forms acetylide via coordination with alkyne. In the next step, azide dipolar addition reaction-click chemistry. In this section, the click binds to the copper followed by the formation of an unconventional reactions, which are catalyzed by different copper catalysts, are copper(III)metallacycle. The energy calculation showed a consider- highlighted. This section has been further sub-divided into five able low energy barrier for the step justifying the higher rate of the classes depending on the type of copper catalysts used either in reaction than its uncatalyzed version. The intermediate then zero, mono or divalent form. M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5259

3.1. Copper halide catalysis protonation.57 Trialkylsilyl-protected alkynes such as 2-silylalkynyl substituted benzofuran 19 and indole 20 have been utilized as Among copper halide catalysts, copper iodide is being fre- a source of alkyne for click method to access benzofuran- and quently used in various transformations. Few reports of copper indole-substituted 1,2,3-triazoles 22 and 23, respectively (Scheme bromide catalysis are also available. Cu(I) combined with Cu(II) 3).10 Here, in situ deprotection of silyl group followed by final cy- salts, other metal complexes or ionic liquids are also used as ef- clization involving click approach afforded the desired triazoles. fective catalytic systems. Most of the reactions proceed smoothly at Aryl iodides 24 are transformed into 4-aryl-1,2,3-triazoles 27 via room temperature. However, there are many reports, which require palladium-catalyzed Sonogashira coupling followed by copper- traditional heating and some are facile upon application of un- catalyzed click reaction using trimethylsilyl acetylene 25 as acety- conventional energy sources like microwave (MW) irradiation and lene surrogate.11 In the first step, there occurs the formation of ultrasound/sonication conditions. Use of co-solvent systems also TMS-protected phenyl acetylenes 26 through Sonogashira reaction. promotes the reactions efficiently. In this part, we categorized the The fact was also confirmed by the isolation of TMS-protected features as systematically as possible so that it would help the phenyl acetylenes in presence of electron-donating functional reader to find the required portion at one stroke. groups such as amino and methoxy, which underwent subsequent Alkyne is one of the indispensable component in click re- deprotection and cycloaddition with azide to afford the substituted actions.7 Yang et al.8 used calcium carbide 14 as a source of acety- triazoles (Scheme 4). lene in copper-catalyzed 1,3-dipolar cycloaddition reaction for the synthesis of 1-aryl-1,2,3-triazoles 15 in 72e95% yields (Scheme 1).

Scheme 4. Sonogashira coupling followed by Cu-catalyzed click reaction.

Scheme 1. CaC2 as a source of acetylene in 1,3-dipolar cycloaddition.

Another method for the direct use of trimethylsilyl-protected Novak and co-workers9a treated acetylene with aliphatic/aro- alkynes via copper(I)-mediated alkyne-azide cycloaddition re- 12 matic azides in Et3N followed by the addition of H2OorD2O in the action was developed by Pericas and co-workers. This method- presence of CuI, which afforded diverse monosubstituted 1,2,3- ology is particularly useful for selective addition of the triazoles 17 or deuterated triazoles 18 (Scheme 2). Here, Et3N trimethylsilyl in front of other silicon-based C(speH protecting played dual role of base and solvent. groups. Ionic liquids as environmentally benign solvents have been employed in click reactions due to their low vapor pressure, effi- ciency to dissolve metal salts in metal-catalyzed reactions, good microwave absorbing capacity and recyclability. Liang and co- workers13 performed a three-component click reaction involving alkynes 28, alkyl/aryl halides 29, and sodium azide to form 1,4- disubstituted 1,2,3-triazoles 31 in presence of CuI in a mixture of ionic liquid [bmim][BF4] and water (Scheme 5).

Scheme 2. Synthesis of simple and deuterated triazoles.

The copper(I)-catalyzed three-component reaction of N-tosyl- hydrazones, terminal alkynes, and azides has been realized in an efficient and regioselective manner for the synthesis of 1,4,5- trisubstituted 1,2,3-triazole derivatives. Mechanistically, the re- action involves the trapping of the copper(I) triazolide intermediate to form a copper carbene and subsequent migratory insertion and

Scheme 5. Synthesis of 1,2,3-triazoles in ionic liquid.

Hagiwara et al.14 developed another heterogeneous catalyst by immobilizing cuprous bromide as a Cu-SILC in the pores of amorphous mercaptopropyl silica gel with the aid of an ionic liquid, [bmim][PF6]. Further, they used it to catalyze Huisgen [3þ2] cycloadditions regioselectively at room temperature in aqueous ethanol. The catalyst can be reused at least six times without losing its activity. In another reaction, various structurally Scheme 3. Synthesis of benzofuran- and indole-substituted 1,2,3-triazoles. diverse organic azides and terminal alkynes were combined in 5260 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 a polyoxygenated ionic liquid (AMMOENG 100Ô) in the presence appropriate azides 41 and alkynes 42 via light induced click re- of CuI to construct 1,4-disubstituted triazole derivatives actions (Scheme 9).19 exclusively.15 Use of non-conventional energy sources like microwave heat- ing, ultrasound and light-induced click reactions have emerged as powerful technique to enhance reaction rate of various chemical transformations. Recently, a few microwave-Cu(I)-coupled click- e chemical methods have been reported.16a d,69,152c Microwave ac- tivation was applied with Cu(I) catalysis to enhance the 1,3-dipolar cycloaddition between azido-20-deoxyribose 32 and terminal al- Scheme 9. Synthesis of 1,4-disubstitutred triazoles via light induced click method. kynes 33 under solvent-free conditions to afford corresponding 4- substituted 1,2,3-triazolyl-nucleosides 34 (Scheme 6). Further UV light is used as an activator for the in situ generated deprotection of the obtained nucleosides was made on their 30- and copper(I)-catalyzed click reaction between azides 44 and alkynes 50-positions to give the corresponding free analogs.16d 45 in the presence of air without reducing agent (Scheme 10).20

Scheme 10. Cu(I)-catalyzed click reaction in the presence of UV light.

Scheme 6. Microwave-Cu(I) coupled click reaction to access 1,2,3-triazoles.

Heterogeneous catalysts are being frequently used in click 17 Reddy and co-workers employed CuI as an efficient catalyst in chemistry. Chi and co-workers21 used ionic polymer supported an ultrasound-accelerated three-component reaction involving al- copper(I) as a reusable catalyst for Huisgen’s 1,3-dipolar cycload- kyl halides 35, terminal alkynes 36, and sodium azide for the dition to produce 1,4-disubstituted 1,2,3-triazoles 49 in high yields regioselective synthesis of l,4-disubstituted 1,2,3-triazoles 37 (Scheme 11). (Scheme 7).

Scheme 11. Polymer supported Cu(I)-catalyzed 1,3-dipolar cycloaddition. Scheme 7. Ultrasound-accelerated synthesis of 1,2,3-triazoles.

A regioselective synthesis of 1,4-diaryl-1H-1,2,3-triazoles 52 Applying click chemistry Chen and co-workers18 synthesized have been developed by copper(I)-catalyzed reaction of diary- 4,5-disubstituted-1,2,3-(NH)-triazoles 40 catalyzed by palladium liodonium salts 50, sodium azide and terminal alkynes (Scheme via Sonogashira coupling/1,3-dipolar cycloaddition involving acid 12).22 Here aryl azides 51 have been generated in situ via the re- chlorides 39, terminal acetylenes 38, and sodium azide in one- action of diaryliodonium salts and sodium azide in polyethylene pot (Scheme 8). Further from 4,5-disubstituted-1,2,3-(NH)-tri- glycol 400 (PEG-400)-water (1:1, v/v) mixture followed by coupling azoles 1,4,5-trisubstituted-1,2,3-(NH)-triazoles could be made with terminal alkyne at room temperature. Girard et al.23 have easily. elaborated a new catalytic system based on copper(I)-doped Wyoming’s montmorillonite in click reaction.

Scheme 8. Palladium-catalyzed synthesis of 4,5-disubstituted-1,2,3-(NH)-triazoles. Scheme 12. Cu(I)-catalyzed reaction of diaryliodonium salts, sodium azide and alkynes.

Diverse triazoles have been prepared in moderate to good yields Dipolar addition reactions are being utilized extensively in bi- via click reactions using a combination of Cu(II) and Cu(0) salts and ology and related fields with small biosurrogates. Zhang and co- sodium ascorbate as a reducing agent. Recently, 1,4-disubstitutred workers24 synthesized several 1,2,3-triazole-linked glyco- 1,2,3-triazoles 43 have been synthesized by the reaction of conjugates 55 in high yields via Cu(I)-mediated 1,3-dipolar M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5261 cycloaddition. Treatment of 2-azidoethyl 2,3,4,6-tetra-O-acetyl-b- D-galactopyranoside 53 with aryl acetylenes 54 in the presence of CuI afforded glycoconjugates 55 in good yields (Scheme 13). Fur- ther, the treatment of azides with glycosyl alkyne in the presence of CuI afforded the desired glycoconjugates 57 in good yields (Scheme 14).

Scheme 13. Synthesis of 1,2,3-triazole-linked glyco-conjugates 55.

Scheme 16. Intramolecular 1,3-dipolar cycloaddition to form spirocyclic compound 67.

refluxing toluene led to the formation of corresponding triglycosy- lated triazoles 71 and 72 (Scheme 17).

Scheme 14. CuI-mediated synthesis of glycoconjugates 57.

Muller€ et al.25 studied the scope of metal-mediated base pairing by developing a new family of 1,2,3-triazole-based ‘click’ nucleo- sides. The utilization of 2-deoxy-b-D-glycosyl azide 58 as a common precursor permitted the modular synthesis of 1,2,3-triazole nu- cleosides (60e63) through CuI-catalyzed Huisgen 1,3-dipolar cy- cloaddition (Scheme 15).

Scheme 17. Thermal cycloaddition of internal alkynes with azides.

Click methods have also been applied toward the synthesis of D- ()-1,4-disubstituted triazolo-carbanucleosides.28 Benhida and co- workers29 described one-pot azideealkyne 1,3-cycloaddition/ electrophilic addition tandem reaction approach leading to a new family of 4,5-difunctionalized triazolyl nucleosides. Two click sys- tems, azido-precursor from regioselective chlorination of thymi- dine and propargyl derivative from selective 30-O-alkylation of thymidine were compiled for 1,3-dipolar cycloaddition to obtain the desired triazole-linked 30e50 thymidine dimer under MW ir- radiation by Zerrouki et al.30 A green approach has been devised to synthesize (1- Scheme 15. CuI-catalyzed Huisgen 1,3-dipolar cycloaddition. substituted-1H-1,2,3-triazol-4-ylmethyl)-dialkylamines 76 through copper(I)-catalyzed three-component reaction based on the Huisgen cycloaddition using amine 73, propargyl halide 74 and 31 Cobb and co-workers26a devised a proficient synthesis of spi- azide 75 in water (Scheme 18). Various copper salts such as rocyclic triazolooxazine nucleosides 67 by the renovation of b-D- CuSO4, CuCl2 and Cu(OAc)2 without any reducing agent, non- psicofuranose to the corresponding azido-derivative 64 followed by copper catalysts like ZnCl2, InCl3, AgCl, AgI, and silver metal were alkylation of the primary alcohol with a range of propargyl bro- also investigated but could not provide the desired triazoles. mides 65. The products 66 of these reactions went through 1,3- In some 1,3-dipolar cycloaddition reactions, mixture of Cu(I) and dipolar addition to produce the protected spirocyclic adducts 67 Cu(II) systems have been extensively used for the synthesis of tri- 32 (Scheme 16). azole nucleus. Chen and co-workers used terminal alkynes, Taourirte and co-workers26b reported synthesis of 1,2,3-triazole phenylboronic acids 77 and sodium azide in a 1,3-dipolar cyclo- and bis(1,2,3-triazoles) acyclonucleoside analogs of Acyclovir. They addition/coupling to afford a series of 1,4,5-trisubstituted 1,2,3- prepared a series of novel 1,2,3-triazole acyclonucleosides linked to triazoles 80 using CuI/CuSO4 as catalyst (Scheme 19). Use of only nucleobases via copper(I)-catalyzed 1,3-dipolar cycloaddition of N- CuSO4 could not trigger the reaction. Various solvents along with 9 propargylpurine, N-1-propargylpyrimidines or N-1- water such as acetone, MeCN, DMF, DMSO, EtOH, MeOH, THF, t- propargylindazoles with the azido-pseudo-sugar by applying mi- BuOH, and 1,4-dioxane were screened. Best result was obtained in e crowave radiation followed by treatment with K2CO3/MeOH. 1,4-dioxane water medium. Diyne byproduct was obtained in this Alternatively, thermal cycloaddition of internal alkynes with case, which was assumed to form as a result of competing Glaser azides were reported by Anand et al.27 Reaction of 1,4-O-bis(4,6-di-O- coupling. Therefore, the course of the reaction was assumed to be acetyl-2,3-dideoxy-a-D-erythro-hex-2-enopyranos-1-yloxy) -but-2- initial Glaser coupling and subsequent 1,3-dipolar cycloaddition. yne 68 with the above two glycosyl azides 69 and 70 separately in But sequential treatment of 1,4-diphenyl buta-1,3-diyne with 5262 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

Scheme 21. CuI-catalyzed synthesis of compound 86.

Grøtli et al.37 synthesized 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3- triazol-4-yl)-substituted pyrazolo[3,4-d]pyrimidin-4-amines via click method. 1,4-Disubstituted 1,2,3-triazoles 89 have been syn- thesized from anti-3-aryl-2,3-dibromopropanoic acids 87 and or- ganic azides in dimethyl sulfoxide using CuI as a catalyst (Scheme Scheme 18. Synthesis of triazolylmethyl-dialkylamines. 22).38 Yang and co-workers39 synthesized 4-aryl-1H-1,2,3- triazoles from anti-3-aryl-2,3-dibromopropanoic acids employing CuI as a catalyst in DMSO.

Scheme 19. Glaser coupling followed by 1,3-dipolar cycloaddition to give compound 80. Scheme 22. Synthesis of 4-aryl-1H-1,2,3-triazoles 89. sodium azide and phenylboronic acid gave no desired product. Treatment of disubstituted triazole with alkyne in the presence of CuI and CuSO4$5H2O also could not trigger the reaction. Thus, CuBr-NCS-mediated multicomponent azideealkyne cycloaddi- a concerted cyclic pathway was assumed for the reaction. tion to synthesize 5-bromo-1,4-disubstituted-1,2,3-triazoles has 1,4-Disubstituted 1,2,3-triazoles have been prepared in high been developed by Li et al.40 Ueda and co-workers41a synthesized yields by one-pot one-carbon homologation of various aldehydes 1,2,4-triazoles by the reaction of 2-aminopyridine and aromatic followed by CuAAC.33 A series of 2-[(4-substituted 1H-1,2,3-triazol- nitriles in presence of Cu(I or II) bromide/acetate as catalyst and 1-yl)-1,4-naphthoquinones 83 were prepared in excellent yields zinc bromide as additive. Diez-Gonzalez and Lal138 used from 2-azido-1,4-naphthoquinone 81 with terminal alkynes 82 in [CuBr(PPh3)3] system for the synthesis of triazoles under neat the presence of a catalytic amount of copper(I) iodide in acetonitrile conditions at room temperature. (Scheme 20).34 Tron and co-workers42 synthesized complex macrocycles in moderate to good yields via click chemistry (Scheme 23). They combined three appropriately designed substrates with a pro- grammed sequence involving acetamide-based three-component reaction followed by copper-catalyzed intramolecular [3þ2] cy- cloaddition of alkyne 92 and azide 91 to give the desired macro- cycle 93.

Scheme 20. CuAAC to generate triazolyl naphthoquinones.

Kuang and co-workers35 synthesized 1-substituted 1,2,3- triazoles by the reaction of azides with propiolic acid via copper- catalyzed click cycloaddition/decarboxylation sequence. Various aryl and vinyl azide derivatives are well tolerated in this protocol. Nguyen and Miles36 employed copper iodide as an efficient catalyst for the synthesis of compound 86 (1,2,3-triazole derivatives of podocarpic acid) at room temperature through click cycloaddition reaction of methyl O-propargylpodocarpate and propargyl O- propargylpodocarpate 84 with different substituted aliphatic and Scheme 23. Synthesis of triazolo fused macrocycles 93 via click method. aromatic azides 85 (Scheme 21). M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5263

Brimble and co-workers43 generated the novel spiroacetal- triazole hybrid structures via cycloaddition of a spiroacetal azide with a series of alkynes. Conte et al.44 synthesized nonlinear 1,4- diaryl-1,2,3-triazoles 98 in a regioselective manner via Cu(I)- catalyzed 1,3-dipolar cycloaddition of aryl azides 95 to terminal aryl acetylenes 94. If the cycloaddition is thermally conduced, a 1:1 mixture of 1,4- and 1,5-disubstituted triazole derivative 96 and 97, respectively is usually obtained (Scheme 24). The 1,4- regioselectivity of the reactions were improved by carrying out them with a catalytic amount of Cu(I) or Cu(II) salts and sodium ascorbate in water or still in encapsulated systems.

Scheme 26. Synthesis of oxepan-2-one substituted triazoles.

Scheme 24. Cu-catalyzed regeoselective synthesis of 1,4 disubstituted 1,2,3-triazoles.

Copper catalysts have been used in modular one-pot multi- component syntheses of fully substituted 1,2,3-triazoles 102 through a chemo- and regio-selective sustainable click reaction/ direct arylation sequence (Scheme 25).45 Frost and co-workers46 displayed the utility of the azido-boronate motif as a modular Scheme 27. Palladium-copper catalyzed synthesis of fused triazoles. building block in the rapid synthesis of drug-like structures employing sequential catalytic azideealkyne cycloaddition under accelerator for the conversions of the CeCu bond-containing in- mild conditions. termediates and buffer the basicity of DIPEA. Thus, it minimizes the 49 drawbacks of CuI/NR3 catalytic system. Dzyuba and co-workers studied effects of the product distribution pattern upon switching base and concentration of reaction bulk in a copper-promoted al- kyne-azide cycloaddition reaction leading to the formation of 5- iodo-triazoles. Generally in base promoted Cu-catalyzed azide-al- kyne cycloadduct iodo-triazoles are valuable synthon for a variety of cross-coupling reactions. Further they are important in modu- lating various recognition processes relevant to supramolecular and biological chemistry. 50 Wang et al. developed a highly efficient novel catalyst SiO2- NHC-Cu(I) for [3þ2] cycloaddition of organic azides 110 and ter- minal alkynes 111. 1 mol % of SiO2-NHC-Cu(I) drives the reaction smoothly to generate the corresponding regiospecific 1,4- Scheme 25. Copper-catalyzed syntheses of 1,2,3-triazoles. disubstituted 1,2,3-triazoles 112 in excellent yields under solvent- free conditions at room temperature (Scheme 28). Further the catalyst can be reused for 10 cycles without any loss of its activity.

Numerous functionalized oxepan-2-ones have been synthesized via Huisgen’s[3þ2] cycloaddition. Since 5-substituted lactones 104 are less sensitive to ring-opening than 3-substituted lactones 103 under the experimental conditions, the click reactions occur only in case of 5-substituted lactones 104 (Scheme 26).47 Chowdhury and co-workers48a synthesized isoindoline fused triazoles 109 from ortho-iodobenzyl azide 107 and acetylenes 108 through palladiumecopper catalysis. The reaction was equally ap- plicable to both aromatic and aliphatic acetylenes. Chiral sugar þ acetylene derivative shows parallel compatibility with the protocol Scheme 28. Use of SiO2-NHC-Cu(I) in [3 2] cycloaddition. (Scheme 27). 55 Shao et al. selected a combination of acid and base system to Brimble and co-workers51 synthesized a series of 1,2,3-triazole promote azide-alkyne cycloaddition in presence of CuI as catalyst. analogs of the nanaomycin family of antibiotics. Treatment of They selected CuI/DIPEA/HOAc system. Here, HOAc acts as the naphthalene azide to various alkynes employing click dipolar 5264 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 cycloaddition followed by oxidation furnished the desired triazole analogs. Click chemistry was also applied in the synthesis of fer- rocene complexes.52 Qian et al. developed a ‘click and activate’ strategy in a four- component, stepwise condensation leading to the synthesis of a library of trisubstituted triazolylpyridazinones 116. The one-pot process comprises of regioselective azide substitution at 2- Scheme 32. Three-component click synthesis of 1,2,3-triazoles involving copper(I) substituted-4,5-dichloropyridazinones, followed by a Cu(I) cata- triazolide intermediate. lyzed 1,2,3-triazole formation that triggered subsequent nucleo- 3.2. Copper sulfate catalysis philic substitution at the neighboring position to achieve three points of diversity (Scheme 29).53 CuSO4 is usually used in two forms either with sodium ascorbate or with Cu(0) system. Trialkylsilyl protected alkynes are also used in presence of CuSO4. Many biological models containing azide or alkyne components have been used successfully under the cyclo- addition methodology. The pioneer Sharpless and co-workers58a performed one ideal example of click method catalyzed by CuSO4 in presence of sodium ascorbate in water and tert-butanol mixture in 2:1 ratio at room temperature. Himo et al.58b performed DFT studies and revealed the stepwise mechanism for the cycloaddi- Scheme 29. Tandem process including click step to synthesize trisubstituted tion. 1,4-Disubstituted 1,2,3-triazoles and 3,4-disubstituted iso- triazolylpyridazinones. xazoles were achieved by the reaction of azides and nitrile oxides in the presence of copper(I) acetylides via an unprecedented metal- Kumar et al. developed a ligand-free copper-catalyzed tandem lacycle intermediates for non-concerted Huisgen’s 1,3-dipolar azide-alkyne cycloaddition (CuAAC), Ullmann-type CeN coupling, cycloaddition. and intramolecular direct arylation leading to the synthesis of 1,2,3- Wang and co-workers58c performed copper(I)-catalyzed 1,3- triazole-fused imidazo[1,2-a]pyridines 120 in a single step in dipolar cycloaddition reaction of nonfluorescent 3- moderate to good yields (Scheme 30).54 azidocoumarins 129 with terminal alkynes 130 to afford intense fluorescent 1,2,3-triazoles 131 (Scheme 33). A library of pure fluo- rescent coumarin dyes have been synthesized applying the above protocol.

Scheme 33. Synthesis of coumarin complexed 1,2,3-triazoles. Scheme 30. Ligand-free copper-catalyzed tandem CuAAC leading to 1,2,3-triazole- fused imidazo[1,2-a]pyridines 120. Moses et al.59 developed an efficient and improved pro- Hu et al. developed a novel acid-base promoted CuAAC where cedure for the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cyclo- a combination of CuI/DIPEA/HOAc was used. HOAc was identified to addition of substituted alkynes with in situ generated aromatic accelerate the conversions of the CeCu bond-containing in- azides from aromatic amines 132. Thus, they obtained 1,4- termediates, thus buffer the basicity of DIPEA which in turn over- disubstituted 1,2,3-triazoles 134 in excellent yields from a vari- comes the drawbacks of the popular catalytic system CuI/NR .55 3 ety of aromatic amines without isolating the azide in- Sun et al. developed a sequential one-pot azide-alkyne click re- termediates (Scheme 34). action followed by tandem aerobic intramolecular CeH amidation leading to the synthesis of triazoloquinazolinones 124 (Scheme 31).56

Scheme 34. Cu(I)-catalyzed synthesis of triazole 134 from aromatic amines.

Scheme 31. Click step in tandem process to synthesize triazoloquinazolinones 124. Wittmann and co-workers60 reported the synthesis of 1,4- disubstituted 1,2,3-triazoles 137 in excellent yields from a variety Wang et al. developed CuI catalyzed regioselective synthesis of of readily available amines 135 via Cu(I)-catalyzed azide-alkyne 1,3- 1,4,5-trisubstituted 1,2,3-triazoles 128 via three-component re- dipolar cycloaddition without the isolation of the azide in- action of N-tosylhydrazones 125, terminal alkynes 126 and azides termediates (Scheme 35). 127. The reaction involves a copper(I) triazolide intermediate that Kumar and co-workers61 synthesized two classes of 1,4- forms copper carbene which suffers subsequent migratory in- disubstituted 1,2,3-triazoles 141 from a-tosyloxy ketones/a-halo sertion and protonation leading to the desired triazole product ketones 138, sodium azide, and terminal alkynes 139 in the pres- (Scheme 32).57 ence of aqueous PEG via one-pot click approach (Scheme 36). M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5265

Scheme 35. Synthesis of 1,2,3-triazoles 137 via diazo transfer followed by azide-alkyne 1,3-dipolar cycloaddition.

Scheme 39. Synthesis of triazolyl substituted alkyl phosphonates.

Scheme 36. Synthesis of 1,2,3-triazoles 141 from a-tosyloxy ketones/a-halo ketones. 154, which were synthesized by direct alkylation of either the corre- sponding substituted phosphono carboxylates or methylene phos- phonocarboxylate with excess of propargyl bromide.65 Furthermore, 62 Shingare et al. synthesized 2-chloro-3-((4-phenyl-1H-1,2,3- compounds 154 were transformed to a series of novel potentially bi- triazol-1-yl)methyl)quinoline derivatives 144 via 1,3-dipolar cy- ologically active 1,2,3-triazole-containing phosphono carboxylates cloaddition reaction of 3-(azidomethyl)-2-chloro-quinoline de- 156 by copper(I)-catalyzed 1,3-dipolar cycloaddition (Scheme 40). rivatives 142 with phenyl acetylene in the presence of Cu(I) catalyst in excellent yield (Scheme 37).

Scheme 40. Synthesis of 1,2,3-triazole-containing phosphono carboxylates.

66 Scheme 37. Synthesis of triazolylmethyl substituted quinolines. Kolarovic et al. developed a tandem practical protocol for the synthesis of 1,4-disubstituted triazoles 160 from aryl halides 157 and alkynoic acids 158 via 1,3-dipolar cycloaddition involving 63 Botta and co-workers applied a microwave-assisted Cu(I)- decarboxylative coupling (Scheme 41). catalyzed click chemistry to generate a small library of enantio- merically pure a-[4-(1-substituted)-1,2,3-triazol-4-yl]benzylaceta- mides 147 from racemic propargyl amines 145 (Scheme 38).

Scheme 41. Synthesis of 1,2,3-triazoles by decarboxylative coupling of alkynoic acids.

67 Weinreb and co-workers prepared TSE-N3 162 in one step from p-tolyl-vinyl sulfone 161 and sodium azide/H2SO4 followed by metal-catalyzed 1,3-dipolar cycloadditions with alkynes 163 to Scheme 38. MW-assisted Cu(I)-catalyzed click reaction. produce TSE-protected 1,2,3-triazoles 164 (Scheme 42).

Delain-Bioton and co-workers64 reported the copper-catalyzed synthesis of 1,2,3-triazolyl-alkyl phosphonates 150 and 153 through Huisgen 1,3-dipolar cycloaddition. Here, alkynyl phos- phonate 148 or azido phosphonate 151 is used as starting material followed by cycloaddition with an azidoalkane 149 or substituted alkyne 152, respectively. High yields of regiospecific products were obtained (Scheme 39). A practical and selective method for the preparation of monopropargyl-substituted phosphonocarboxylate (PC) has been developed by the addition of sodium acetylenide to ethylidene phosphonate and corresponding ethyl(propargyl)-, tri- Scheme 42. Synthesis of TSE-protected 1,2,3-triazoles. fluoromethyl(propargyl)- and dipropargyl-substituted derivatives 5266 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

Ramana et al.68 utilized activated fluorobenzenes 166 to react with azide nucleophile to form aryl azides, which upon treatment with alkynes 165 afforded 1,4-substituted triazoles 167. Cu(I) cat- alyst was used to catalyze the SNAr reaction followed by [3þ2] cycloaddition (Scheme 43).

Scheme 43. Cu(I)-catalyzed SNAr followed by [3þ2] cycloaddition reaction.

Scheme 46. Reaction of propargylated diazenes with 2-(azidomethyl) pyridine.

Microwave-assisted three-component one-pot reaction has is stepwise Swern oxidation/OhiraeBestman alkynylation of read- been developed to prepare a series of 1,4-disubstituted-1,2,3- ily available 4-hydroxymethyl-1,2,3-triazoles and the second one is triazoles from corresponding alkyl halides 168, sodium azide, and the stepwise cycloaddition of TMS-1,4-butadiyne. The protocol is alkynes 169. The azides are generated in situ from corresponding compatible with orthogonally protected and functionalized halides, followed by click cycloaddition to give the corresponding saccharide-peptide hybrids. 1-N-Alkyl-4-aryl-1,2,3-triazoles 182 1,4-disubstituted-1,2,3-triazoles 171 (Scheme 44).69 have been prepared from in situ generated alkyl azide and alkyne 181 followed by copper(I)-catalyzed click cycloaddition. The un- desired 1,5-disubstituted cycloadduct 183 was formed in minor amount (Scheme 47).73

Scheme 44. Microwave-assisted synthesis of 1,4-disubstituted-1,2,3-triazoles.

Chandrasekhar et al.70 devised a three-component coupling protocol for the synthesis of a series of 1,4-disubstituted-1,2,3- triazoles 175 from the corresponding acetylated BayliseHillman adducts 172, sodium azide and terminal alkynes 173 (Scheme 45). Scheme 47. Copper(I)-catalyzed click reaction. Kosmrlj et al.71 prepared propargyl functionalized diazenes 176 and utilized as alkyne click component in copper-catalyzed azide- alkyne cycloadditions (CuAAC) with 2-(azidomethyl) pyridine 177 Simpson et al.74 developed one-pot three-step procedure for the 0 0 to give the substituted triazoles 178. Reaction with azidoalkyl- synthesis of 1,1 -disubstituted-4,4 -linked unsymmetrical bis(1,2,3- amines 179 completed within few minutes by copper(II)sulfate, and triazoles), which act as good coordinating ligand for transition does not require any reducing agent. Whereas 2-(azidomethyl) metals. Here, they have employed sequential copper-catalyzed pyridine takes nearly 2e24 h to complete the reaction in the azide-alkyne cycloaddition and deprotection steps on a monosilyl presence of metallic copper (Scheme 46). butadiyne. Fletcher and co-workers75 developed two-step one-pot reaction conditions for the synthesis of 1-substituted-1,2,3- triazoles 186 up to 90% yields. It involves potassium carbonate- catalyzed deprotection of trimethylsilyl acetylene 184 followed by Cu-catalyzed Huisgen 1,3-dipolar cycloaddition under aqueous conditions with methanol as the alcoholic aqueous co-solvent. Both alkyl and aryl azide reactants 185, including analogs with electron- donating and electron-withdrawing functionalities were tolerated successfully in this protocol (Scheme 48). Yao et al.76 developed an assembly of small molecule-based MMP inhibitors containing rhodanine 190 warheads using one- e Scheme 45. Synthesis of 1,2,3-triazoles from acetylated Baylis Hillman adducts. pot click chemistry (Scheme 49). Aucagne and co-workers made an in-depth study and systematic comparison of five classical silyl Fratila et al.72 developed a new strategy for the synthesis of alkyne protective groups to examine their potential in multiple unsymmetrically 1,10-disubstituted 4,40-bis-1H-1,2,3-triazoles from successive copper(I)-catalyzed alkyne-azide cycloaddition 4-ethynyl-1,2,3-triazoles and azides via double-click strategy. One (CuAAC).77 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5267

C(2)-Propargylsubstituted pentacyclic triterpenoids 194 were successfully transformed to conjugates with 1,2,3-triazole-con- taining b-D-glucopyranosides 196 via Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction (Scheme 51).79 1,2,3-Triazole-containing b- D-glucopyranosides generated by 1,3-dipolar addition of pentacyclic triterpenoids and azide-sugars may act as antitumor agents.

Scheme 48. Synthesis of 1-substituted-1,2,3-triazoles.

Scheme 49. Synthesis of Rhodanine containing 1,2,3-triazoles. Scheme 51. Synthesis of 1,2,3-triazole-containing b-D-glucopyranosides 196 via Cu(I)- catalyzed CuAAC.

Substituted 1,2,3-triazoles has been synthesized by involving 80 one-pot direct azidation of allylic/benzylic alcohols or their methyl Song and co-workers synthesized a series of triazole-linked ethers followed by the click reaction (Scheme 50). Two methods ester-type glycolipids in excellent yields via two-step sequence were successfully developed for synthesizing various substituted involving microwave accelerated click strategy and debenzylation. 1,2,3-triazole derivatives 193 directly from various allylic/benzylic Numerous O-alkynyl fatty esters and 1-azido-tetra-O-benzyl-b-D- alcohols without isolating the corresponding azides. The first glucosides are well tolerated to 1,3-dipolar cycloaddition reaction. method (method A) involved magnetic nano Fe3O4-catalylzed di- Vitamin D ring system synthons with triazole rings in their side þ rect azidation of various allylic/benzylic alcohols with TMSN3 as the chains has been prepared. Triazole ring was formed via a [3 2] first step followed by the Cu-catalyzed click reaction of the corre- cycloaddition of a vitamin D side chain terminal azide with a ter- 81 82 sponding azides with alkynes as the second step. The second minal acetylene. Wang et al. developed a one-pot synthesis of method (method B) involved the Cu(OTf)2-catalyzed direct azida- 1,2,3-triazole-linked glycoconjugates via Cu(I)-catalyzed 1,3- tion of various allylic/benzylic alcohols 191 and methyl ethers of dipolar cycloaddition as the key step. A number of neo- allylic/benzylic alcohols with TMSN3 192 as the first step followed glycoconjugates derived from unprotected saccharides or per- by the click reaction of the corresponding azides with alkynes as acetylated saccharides have been prepared by this method. the second step.78 Several applications of click chemistry in biological and related fields have already been reported. Here some more examples are discussed. Agrofoglio et al.83 developed the synthesis of 1,2,3-triazolo- 30-deoxy-4’-hydroxymethyl carbanucleosides under different re- action conditions and diverse modulations on the heterocycle residues by the application of click chemistry. Brunet and co-workers84 syn- thesized a new ligand bearing the bis-triazolylpyridine motif and pendant phosphonate groups by means of click chemistry. A new TTFePDI conjugate has been synthesized from an azide- functionalized TTF and an acetylenic PDI employing a Cu(I)- catalyzed Huisgen-Meldal-Sharplessreaction a kindof click method.85 Hughes et al.86 have prepared a series of orthogonally protected 1,4-disubstituted-1,2,3-triazoles from the corresponding alkynols and trialkylsilyl-propargyl azides via 1,3-dipolar cycloaddition. Further they have selectively deprotected the cycloadducts and extended in a stepwise manner to form oligomeric peptidomimetic compounds via further click reactions. A diverse novel set of P,N- type ligand family (Click Phine) 199 have been furnished using the Cu(I)-catalyzed azide-alkyne click cycloaddition (Scheme 52).87 Hackenberger et al.88 reported the synthesis of borane- protected triazole phosphonites 202 in the presence of CuSO4 tris(3-hydroxypropyltriazolylmethyl)amine and sodium ascorbate t in H2O/ BuOH at room temperature (Scheme 53). Shreeve and co-workers89,90 disclosed that 1- pentafluorosulfanyl acetylene and its derivatives react with azide Scheme 50. One-pot tandem azidation/click reaction leading to the synthesis of or diazomethane giving rise to SF5-substituted 1,2,3-triazoles or 91 substituted 1,2,3-triazoles 193. pyrazoles through click chemistry. Pore and co-workers designed 5268 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

of 12- and 14-membered cyclic peptidotriazoles (209 and 214 re- spectively) differs slightly in the substrate variation. Moses and co-workers95 performed one-pot azidation of ani- lines with t-BuONO and TMSN3. Thus, in situ generated azides under microwave irradiation afforded 1,4-disubstituted 1,2,3- triazoles. Fletcher and co-workers96 described the synthesis of a series of 1-allylated and 1-benzylated 1,2,3-triazoles in 74e98% yields with various substituents at the 4-position. The reaction Scheme 52. Synthesis of P,N-type ligand family having 1,2,3-triazole unit. course follows a tandem process involving the nucleophilic sub- stitution of allyl chloride and benzyl bromide with sodium azide to form organic azide intermediates followed by Cu-catalyzed Huis- gen 1,3-dipolar cycloaddition with alkyne in one pot. Orthogonally N-protected (Boc and Cbz) 4-(1,2,3-triazol-4-yl)-substituted 3- aminopiperidines were prepared from piperidine building block by using copper-catalyzed Huisgen 1,3-dipolar cycloaddition as a key step.97a In a study, Shao et al. have shown remarkable pro- moting efficiency of carboxylic acids in all three key steps in the catalytic cycle of CuAAC. Among different carboxylic acids benzoic acid showed the best promotion activity. On the other side, the acids that can form strong chelate to Cu(I) ion could not serve for this purpose.97b Raic-Malic and co-workers applied microwave assisted Cu(I)- catalyzed click chemistry to prepare novel conformationally re- stricted pyrimidine derivatives 219 with a 1,2,3-triazolyl scaffold 98 Scheme 53. Synthesis of borane-protected 1,2,3-triazole phosphonites. bound via Z- and E-2-butenyl spacers (Scheme 55). novel fluconazole/bile acid conjugates and carried out their regio- selective synthesis in very high yield via Cu(I)-catalyzed in- termolecular 1,3-dipolar cycloaddition. Voelcker et al.92 investigated the catalytic activity of various copper (Cu)-loaded PAMAM dendrimers towards click chemistry and found faster conversion upon using PAMAM dendrimers as macromolecular Cu(I) ligands compared to traditional small molecular ligand sys- tems. Another method for the preparation of 1,4-disubstituted 1,2,3-triazoles from aldehyde and amine has been developed by Maisonneuve and Xie.93 During the course of the reaction in situ transformation of aldehyde into alkyne occurs followed by diazo transfer of amine into azide and subsequent cycloaddition. Bahulayan et al. have demonstrated a two-step synthesis of 12- and 14-membered cyclic peptidotriazoles (peptidomimetics) by combining a one pot four-component reaction and an intra- molecular [3þ2] azideealkyne click cycloaddition reaction strategy (Scheme 54).94 Structural features as well as the preliminary as- Scheme 55. Microwave assisted CuAAC to access conformationally restricted pyrimi- sessment of drug-likeness contributing parameters indicate that, dine derivatives. the macrocycles can be used in the search for drug leads. Synthesis Allard and co-workers have revealed that a mono-adduct ful- lerene building block bearing an alkyne moiety as well as a mal- eimide unit can be orthogonally clicked through stepwise or one pot processes using benzyl azide and 1-octanethiol under simple and mild conditions (Scheme 56).99 This new strategy exposed the way for the synthesis of a wide range of fullerene derivatives de- veloping a set of orthogonal reactions.

3.3. Copper acetate catalysis

Deobald et al.100 examined the use of organoselenium com- pounds in the copper catalyzed Huisgen 1,3-dipolar cycloaddition of azido arylselenides 225 with various alkynes 226. In this study, they synthesized arylseleno-1,2,3-triazoles 227 in excellent yields by the reaction of amino arylselenides 224 with iso-pentylnitrite and trimethylsilyl azide followed by copper-catalyzed 1,3-dipolar cycloaddition (Scheme 57). 101 b Scheme 54. MCR and click methods for the synthesis of 14 and 12-membered Reddy et al. synthesized -hydroxy 1,2,3-triazoles 231 from macrocycles. in situ generated 1,2-azidols 229 employing two sequential click M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5269

Scheme 59. Cu(II)-catalyzed aza-Michael addition.

of a click reaction employing ynamides. Various highly function- alized azides were treated with N-benzyl/N-tosyl ynamide to give Scheme 56. Orthogonal click functionalization of compound 220 through step-wise or the corresponding triazole adducts in high yields and regiose- one-pot process. lectivity (Scheme 60).

Scheme 60. Synthesis of 4-amino-1,2,3-triazoles 238.

Crousse and co-workers104 performed a sequential one-pot re- action of gem-chloroamine CF3CH(Cl)NHAc 239 with NaN3 to afford trifluoromethyl azido compound, which upon reaction with al- kynes 241 via Huisgen 1,3-dipolar cycloaddition provided 1,4- disubstitued 1,2,3-triazoles 242 in 74e87% yield. The reaction was catalyzed by Cu(II) species (Cu(OAc)2, 10 mol %) without any re- Scheme 57. Synthesis of arylseleno-1,2,3-triazoles. ducing agent (Scheme 61). reactions in high yields. Different Cu(I) and Cu(II) containing cat- alysts were investigated and high regioselectivity was obtained from 10 mol % of Cu(OAc)2.H2O in water at room temperature (Scheme 58).

Scheme 61. Reaction of gem-chloroamine CF3CH(Cl)NHAc with NaN3 to give 1,2,3- triazoles 242.

Use of selenium compounds, in click chemistry by copper cat- alyzed 1,3-dipolar cycloaddition of azidomethyl arylselenides with alkynes have been demonstrated by Alves and group (Scheme b Scheme 58. Synthesis of -hydroxy 1,2,3-triazoles. 62).105 The selenium-triazoles 245 were selectively prepared in good yields under mild conditions via reaction of azidomethyl arylselenides 243 with a range of terminal alkynes 244. This click Favi et al.102 reported a one-pot Cu(II)-catalyzed aza-Michael procedure minimizes the energy plea; as well the reaction time addition of trimethylsilyl azide to 1,2-diaza-1,3-dienes 232 and could be reduced from several hours to few minutes using MW Cu(I)-catalyzed 1,3-dipolar cycloaddition of in situ generated azi- irradiation. By this methodology new selenium-containing tri- dohydrazones with alkynes 234 to form 1,2,3-triazole derivatives azoles have been efficiently synthesized with potential application 235 (Scheme 59). in biological studies. Cintrat et al.103 synthesized a series of 1-substituted 4-amino Fiandanese et al.106 synthesized 4-alkynyl-1,2,3-triazoles 248 1,2,3-triazoles 238 via [3þ2] cycloaddition between azides 236 and novel unsymmetrically substituted 4,40-bi-1,2,3-triazole de- and ynamides 237. The copper-catalyzed process was the example rivatives 250 via click method. Here, 1-trimethylsilyl-1,3-butadiyne 5270 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

Scheme 62. Synthesis of 1-(arylseleno-methyl)-1,2,3-triazoles 245.

246 was treated with several azides 247 leading to 4-(silylalkynyl)- Scheme 65. Sequential copper-catalyzed synthesis of functionalized 1,2,3-triazoles 1,2,3-triazoles 248. Later on it was transformed into 4-arylalkynyl- from DHPMs. 1,2,3-triazoles by a Pd-catalyzed coupling reaction with aryl halides or into novel 4,40-bi-1,2,3-triazole derivatives 250 by a subsequent cyclization reaction with azides (Scheme 63). Kantam et al.107 synthesized 1,2,3-triazoles in water using cheaply available Cu(OAc)2 without any additional reducing agents in a highly regioselective manner.

Scheme 66. Sequential synthesis of N-functionalized 1,2,3-triazoles with amide.

azide components in Cu-catalyzed click reaction with alkynes 259. Thus, they synthesized a wide variety of N-heterocyclic derivatives of 1,2,3-triazoles 260 (Scheme 67).

Scheme 67. Copper triflate-catalyzed synthesis of 1,2,3-triazoles.

Scheme 63. Synthesis of unsymmetrically substituted 4,40-bi-1,2,3-triazoles. Glycosyl azides were prepared in situ from glucal 261 and tri- Hu et al. synthesized 1-(pyridin-2-yl)-1,2,3-triazoles 253 from methylsilyl azide via Ferrier rearrangement. In the next step, it 6-substituted tetrazolo-[1,5-a]pyridines 251 via copper(I)- undergoes coupling with alkynes 262 to form 1,2,3-triazole-linked catalyzed azideealkyne cycloaddition (CuAAC) using copper(I) ac- glycoconjugates 263 or 264 in moderate stereoselectivity under 111 etate as catalyst (Scheme 64).108 neutral conditions (Scheme 68).

Scheme 64. Click synthesis of 1-(pyridin-2-yl)-1,2,3-triazoles from 6-substituted tet- razolo-[1,5-a]pyridines.

Wang et al. have reported a one-pot two-step method for gen- eration of a series of functionalized 1,2,3-triazoles derivatives (255 and 257) in decent yields (Schemes 65 and 66).109 Specially, N- functionalized 1,2,3-triazoles with amide or dihydropyrimidinone Scheme 68. Synthesis of 1,2,3-triazole-linked glyco-conjugates. were prepared by this procedure. This technique reduces the need to handle organic halides or organic azides, as they are generated in situ, making this process more user-friendly and nontoxic.

Yadav et al.112 synthesized alkoxy-1,2,3-triazoles 269 by one-pot 3.4. Copper triflate catalysis four-component coupling of aldehyde 265, alcohol 266, trime- thylsilyl azide 268, and alkyne 267 via acetal formation, azidation, Gevorgyan and co-workers110 disclosed efficient use of various and click reaction sequence. Copper(II) triflate and copper metal pyrido-, quinolino-, pyrazino-, and quinoxalinotetrazoles 258 as catalyzed the reaction in acetonitrile providing a wide range of M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5271 triazoles (Scheme 69). Mantellini and co-workers113 have demon- Mandal et al. described the synthesis of a copper(I) chloro strated some reactions using click chemistry. Fukuzawa et al.114 complex using an abnormal N-heterocyclic carbene (aNHC) salt, developed a method for the synthesis of 1,4-disubstituted 1,2,3- 1,3-bis(2,6-diisopropylphenyl)-2,4-diphenylimidazolium. Conse- triazoles catalyzed by copper(II) triflate via substitution of ben- quently they used 0.005 mol % of the complex as catalyst in the click zylic acetates by TMSN3 followed by 1,3-dipolar addition with an reactions of azides with alkynes to give 1,4-disubstituted 1,2,3- alkyne. triazoles in excellent yields at room temperature under solvent- free conditions.116 Song et al. synthesized ZnOeCuO core-branch hybrid nano- particles by copper oxide growth and controlled oxidation on ZnO nanospheres and used their catalytic activity and stability for ultrasound-assisted [3þ2] azide-alkyne cycloaddition reactions. They found remarkable enhancement of catalytic activity due to the high surface area and active facets of the CuO branches.117 Chen et al. used [Cu(phen)(PPh3)2]NO3 (1 mol %) as the catalyst in azi- deealkyne cycloaddition (CuAAC) reaction under solvent-free conditions. Within 2e25 min good to excellent yields of 1,4- disubstituted 1,2,3-triazoles were obtained.118 Straub et al. re- ported a three-step synthesis of two representative bis-NHC- dicopper complexes as well as their catalytic performance in the azideealkyne cycloaddition.119 Fabbrizzi and co-workers120 employed (2-aminoarenethiolato) copper(I) complex (1.0 mol %) as a catalyst in CuAAC click method in Scheme 69. Synthesis of 1-alkoxy-1,2,3-triazoles. an organic solvent. Alonso and co-workers121 showed catalytic activity of copper nanoparticles on activated carbon. They used the b 3.5. Use of other copper catalysts catalyst in multi-component synthesis of -hydroxy-1,2,3-triazoles 276 or 277 from a variety of epoxides 273 and alkynes 274 in water 115 (Scheme 71). Vincent et al. reported that copper (I) complex [Cu(C186tren)] Br (C186tren¼tris(2-dioctadecylaminoethyl) amine), which ex- hibits a good stability towards aerobic conditions is a versatile, highly reactive, and recyclable catalyst for the Huisgen cycloaddi- tion of azides with terminal/internal alkynes and is a useful catalyst for the preparation of click dendrimers (Fig. 3).

N Br N Cu N C18H37 C18H37 C18H37 N C18H37

C18H37 C18H37 Scheme 71. Synthesis of b-hydroxy-1,2,3-triazoles 277.

Fig. 3. Structure of [Cu(C186tren)]Br (C186tren¼tris(2-dioctadecyl aminoethyl)amine). Nageswar and his group developed a method for the prepara- The reactions of azides 270 and acetylenes 271 were carried out tion of 1,2,3-triazoles 281 using magnetically separable copper 122 efficiently in solvents like toluene or n-octane (due to polarity of ferrite nanoparticles as the catalyst (Scheme 72). This one pot the compound selective precipitation of the products occurs from protocol to access 1,2,3-triazoles 281 involves initial substitution of low polar solvents) using 0.05 mol % of catalyst, which afforded the benzyl halides 278 with sodium azide, which generated in situ benzyl azides followed by copper ferrite catalyzed cycloaddition corresponding 1,4-disubstituted-1,2,3-triazoles 272 in good to ex- cellent yields (Scheme 70). Finally, they also investigated the syn- reaction with alkynes 280 in water at 70 C. Most remarkably here thesized copper-complex as catalyst in the synthesis of a 1,2,3- tap water has been used as the solvent. triazole-linked dendrimer.

Scheme 70. Use of copper-complex toward the synthesis of 1,4-disubstituted-1,2,3- Scheme 72. Synthesis of 1,2,3-triazoles using CuFe2O4 nanoparticles in tap water. triazoles. 5272 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

123 Fukuzawa and co-workers prepared Cu-complexes of iso- CuCl(PPh3)3 (10 mol %)]. Later on, the product was further deal- cyanate, and employed as catalysts in click reactions of azides with lylated by the treatment of ozone with ruthenium catalyst to get alkynes to give 1,4-disubstituted 1,2,3-triazoles. For the reaction the substituted triazole 291 (Scheme 75). between sterically hindered azides and alkynes they observed that CuCl(TPh) has a particular efficiency to catalyze the reaction. Orgueira et al.124a devised a method for the regioselective synthesis of highly functionalized 1,2,3-triazoles 284 from terminal alkynes 282 and azides 283 in the presence of Cu(0) catalyst. They gener- ated catalytic Cu(I) species by the reaction of 10 mol % copper nanosize activated powder and 1 equiv of an amine hydrochloride salt (Scheme 73). They added an amine hydrochloride salt into the reaction mixture to enhance the dissolution of copper metal, and enhanced the formation of the Cu(I)-acetylide intermediate, which is required for the regioselective cycloaddition.

Scheme 75. Use of copper(I)-N-heterocyclic carbene in CuAAC reaction.

Boons et al.127d demonstrated the use of Pd(0)-Cu(I) catalyst in Sonogashira cross-coupling-desilylation-cycloaddition reaction se- quence providing 1,4-disubstituted 1,2,3-triazoles in good yields. A heterogeneous copper catalyst by immobilizing copper nano- particles in aluminum oxyhydroxide fiber has been developed and applied to [3þ2] Huisgen cycloaddition at room temperature, which promoted the reaction smoothly. The catalyst is effective for both nonactivated alkynes as well as activated ones with various azides, Scheme 73. Use of copper nanosize activated powder in dipolar cycloaddition and are recycled five times with comparable catalytic efficacy in reaction. each case.127e Xu et al. used Cu/Pd transmetalation relay catalysis in three-component click reaction of azide, alkyne, and aryl halide to 124b Yus and co-workers disclosed that copper nanoparticles synthesize a variety of 1,4,5-trisubstituted 1,2,3-triazoles in one catalyze the 1,3-dipolar cycloaddition of azides and alkynes with step. As CuAAC generally works only on terminal alkynes, thus the a comparable rate to those of microwave chemistry. b-Hydroxy- approach is supposed to serve as an alternative solution for the triazoles with high regioselectivity in excellent yields are prepared problem of the click reactions of internal alkynes (Scheme 76).128 by Yadav et al.125a via click method where 2-azidoalcohols derived in situ from epoxides and sodium azide undergo smooth coupling with alkynes under neutral conditions. Reiser and co-workers125b used copper(I) isonitrile complex as heterogeneous catalyst for the Huisgen azide-alkyne 1,3-dipolar cycloaddition under mild conditions in water. The catalyst can be recycled for at least five runs without significant loss of activity. Lipshutz et al.126 have developed a new heterogeneous catalyst consisting of copper and nickel oxide particles supported within charcoal, which catalyzes azide-alkyne click reactions nicely. Scheme 76. Cu/Pd transmetalation relay catalysis in three-component click reaction. Through the series of compounds expected 1,4-regioselectivity was uniformly observed (Scheme 74). In another report Kong et al. prepared polyvinylpyrrolidone (PVP) coated copper(I) oxide nanoparticle and used them to catalyze azide- alkyne click reactions in water under aerobic conditions. It was found to be more efficient catalytic system in water and less toxic than the commonly used CuSO4/reductant catalyst systems.129 Lipshutz et al.100d used 10 mol % copper in charcoal (Cu/C) to prepare triazoles 300 from azides and alkynes in 0.5 M dioxane. Under basic condi- tions, the reaction accelerates decreasing the reaction time drasti- cally. In case of microwave irradiation at elevated temperature Scheme 74. Cu, nickel oxide and charcoal supported CuAAC. reaction time also decreases significantly. Later in another report, Bruce H. Lipshutz et al. used recyclable Cu/C to generate various azides in situ from the corresponding amines and simultaneously Copper nanoparticles have been used to catalyze the 1,3-dipolar involve them in [3þ2] cycloaddition with terminal alkynes leading to cycloaddition of a variety of azides and alkynes forming corre- the synthesis of triazoles in good yields (Scheme 77).130 sponding 1,2,3-triazoles in excellent yields.127a Further a combina- tion of copper(I)-N-heterocyclic carbene complex and aromatic N- donors were utilized for azide-alkyne cycloaddition (CuAAC) under reductant-free conditions.127b Yamamoto et al.127c accomplished a click method through a three-component coupling (TCC) reaction between alkynes 288, allyl methyl carbonate 289, and TMSN3 to get allyltriazoles 290 mediated by a bimetallic catalyst Pd(0)-Cu(I) Scheme 77. Copper in charcoal (Cu/C) as catalyst in click reaction. [i.e., Pd2(dba)3.CHCl3 (2.5 mol %), P(OPh)3 (20 mol %), and M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5273

In another report Alonso et al. also described click method cycloaddition reactions under strict click conditions. The process catalyzed by copper nanoparticles on activated carbon to synthe- required neither any additive nor any purification step to isolate size 1,2,3-triazoles from organic halides, diazonium salts, and aro- pure 1,2,3-triazole products.138 matic amines in water.131,132 Santoyo-Gonzalez et al. developed Yagci et al. combined thioxanthone carboxylate moiety with a one-pot, three-component tandem azidation/CuAAC of cyclic copper(II) ions by ion exchange reaction to synthesize copper(II) sulfates or cyclic sulfamidates the fast and efficient preparation of thioxanthone carboxylate 310. Subsequently, it was used as an ef- (alkyl sulfate)- and (alkyl sulfamidate)-1H-1,2,3-triazoles 304.Un- ficient photocatalyst in photochemically induced copper(I)- der microwave irradiation Si-BPMA$Cuþ or Si-BPA$Cuþ served as catalyzed azide-alkyne cycloaddition (CuAAC) reaction, which is the excellent heterogeneous catalyst to simplify the manipulation devoid of any additional ligands. It was believed that during the and the isolation procedure (Scheme 78).133 catalytic process, intramolecular photoinduced electron transfer was stimulated to reduce copper(II) ions to generate copper(I) species, which catalyzes the CuAAC reaction (Scheme 80).139

Scheme 80. Copper(II) thioxanthone carboxylate catalyzed photochemical azide- alkyne cycloaddition (CuAAC). þ þ Scheme 78. Si-BPMA$Cu /Si-BPA$Cu heterogeneous copper catalyst in click reaction. In another report Yamamoto et al. prepared nanoporous copper (CuNPore) catalysts with tunable nanoporosity from Cu30Mn70 al- loy by controlling the de-alloying temperature under free corrosion 1,4,5-Trisubstituted 5-dialkylamino-1,2,3-triazoles are compar- conditions. They showed that the tunable nanoporosity of CuNPore atively difficult to prepare probably due to the strong oxidizing significantly enhanced its catalytic activity in click chemistry property of the amine electrophile (R Nþ) or the low reactivity of 2 without using any supports and bases.140 the MeC bond in the intermediate. Hu et al. used showed facile Page et al. developed a copper catalysed azideealkyne cyclo- formation of reactive 5-copper(I)-1,2,3-triazole intermediate in the addition (CuAAC) in liquid ammonia. Compared with that in con- presence of the amine (R Nþ) electrophile by using polymeric 2 ventional solvents only 0.5 mol % copper(I) catalyst give exclusively complex 1-copper(I)-alkyne as a substrate leading to the synthesis 1,4-substituted 1,2,3-triazoles with excellent yields (up to 99%). of 1,4,5-trisubstituted 5-dialkylamino-1,2,3-triazoles.134 From deuterium exchange experiments with phenyl acetylene-d1 it Xia et al. prepared cross-linked polymeric ionic liquid material- was revealed that the acidity of the alkyne is increased around supported copper (Cu-CPSIL), imidazolium loaded Merrifield resin- 1000-fold with catalytic amount of copper(I) in liquid ammonia.141 supported copper (Cu-PSIL) and silica dispersed CuO (CuO/SiO2) Miquel A. Pericas et al. prepared a library of modular tris(triazolyl) and used them as efficient catalysts for the one-pot synthesis of 1,4- methane ligands and screened them in copper catalysed azide- disubsituted-1,2,3-triazoles from the reaction of alkyl halides with ealkyne cycloaddition (CuAAC).142 sodium azide and terminal alkynes in water at room tempera- Trabocchi and his group proposed a versatile ‘click-based’ ap- ture.135 Vijayakumar et al. synthesized and characterized CuO proach in developing libraries of densely functionalized scaffolds nanoparticles and consequently applied it as an efficient reusable containing three fragments (Scheme 81).143 By this process Click catalyst in click chemistry to prepare xanthene substituted 1,2,3- chemistry has been used for modular strategy involving only re- triazoles 307 (Scheme 79).136 actions performed in mild conditions starting from readily available building blocks in order to synthesize highly functionalized

Scheme 79. Efficient reusable CuO nanoparticles-catalyzed click synthesis of xanthene substituted 1,2,3-triazoles 307.

Tale et al. developed (1-(4-methoxybenzyl)-1-H-1,2,3-triazol-4- yl)methanol (MBHTM) as efficient click ligand to accelerate copper- catalyzed [3þ2] azideealkyne cycloaddition at low catalyst loading (catalyst loading decreases from 10 to w1 mol %).137 Silvia Díez- e Gonzalez et al. used minute amount (0.5 mol % 50 ppm) of com- Scheme 81. Copper (I) catalyzed azide-alkyne cycloaddition (CuAAC) to achieve the mercially available [CuBr(PPh3)3] to catalyze azide-alkyne three-fragment-bearing scaffolds. 5274 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 molecules which are suitable candidates for high-throughput 4-Aryl-5-cyano- or 4-aryl-5-carbethoxy-1H-1,2,3-triazoles 326 screening and multiple receptors targeting in a drug discovery. are synthesized by [3þ2] cycloaddition reactions of 2-aryl-1-cyano- or 2-aryl-1-carbethoxy-1-nitroethenes 324 with TMSN3 under solvent-free conditions in presence of TBAF catalyst (Scheme 4. Use of other non-copper catalysts 85).146b

Limitations of copper-catalyzed click methods mainly arise in the field of bioconjugation and in vivo imaging due to the toxic nature of copper. The reaction between azides and alkynes in bi- ological environment is rarely observed due to their inertness in absence of copper. Therefore, the importance of copper-free click reactions has been realized. However, only limited click reactions are reported that are not catalyzed by copper. In this section, we will discuss some dipolar additions used in organic synthesis that are not catalyzed by copper catalysts. Scheme 85. Synthesis of 4-aryl-5-cyano-/4-aryl-5-carbethoxy-1H-1,2,3-triazoles 326. Synthesis of substituted 1H-1,2,3-triazole-4-carboxylic ester 317 have been performed by the reaction of aryl azides 315, ethyl 4- Novel tricyclic 1,2,3-triazoles starting from cyclic epoxides via chloro-3-oxobutanoate 316, and either O-orS-nucleophiles in the the sequential azidolysis, propargylation and 1,3-dipolar cycload- presence of a base catalyst. It has been observed that the reaction dition without any copper catalyst have been synthesized.147 most probably proceeds via [3þ2] cyclocondensation between aryl Jagerovic et al. synthesized a series of new N1-, N2- and N3- azide 315 and ethyl 4-chloro-3-oxobutanoate 316 followed by nu- substituted 1,2,3-triazole derivatives by cycloaddition of butyltin cleophilic substitution of chlorine in the chloromethyl group azide with substituted alkynes followed by N-alkylation.148a Fokin (Scheme 82).144 and co-workers148b synthesized 1,5-diarylsubstituted 1,2,3- triazoles 329 in high yield from aryl azides 328 and terminal al- kynes 327 in DMSO catalyzed by tetraalkylammonium hydroxide (Scheme 86).

Scheme 82. Synthesis of 1H-1,2,3-triazole-4-carboxylic esters 317.

Wu et al.145 carried out a base-promoted cycloaddition reaction between aryl azide 315 trimethylsilyl alkynes 318 to generate 1,5- disubstituted 1,2,3-triazoles 319 regioselectively in good yields at ambient temperature (Scheme 83).

Scheme 86. Tetraalkylammonium hydroxide catalyzed synthesis of 1,5-disubstituted 1,2,3-triazoles.

Fokin and co-workers149a surveyed the catalytic activity of a series of ruthenium(II) complexes in azide-alkyne cycloadditions and found that the [Cp*RuCl]4 complexes to be most reactive to- wards this cycloaddition. In the presence of such type of catalysts Scheme 83. Base-promoted synthesis of 1,2,3-triazoles 319. secondary azides react with terminal alkynes producing a large range of 1,5-disubstituted 1,2,3-triazoles. Herein, some examples of click reactions employing ruthenium catalysts have been discussed. Lewis base-catalyzed three-component cascade reaction for the Takasu and co-workers prepared trifunctional thioureas bearing 1,5-disubstituted triazole tether by Ru-catalyzed Huisgen cycload- synthesis of diverse 4,5-disubstituted-1,2,3-(NH)-triazoles 323 149b have been reported in good to excellent yields.146a The newly dition (Scheme 87). synthesized (NH)-triazoles 323 contain C-4 vinyl group, which can be further converted into other triazole derivatives (Scheme 84).

Scheme 87. Use of ruthenium(II) complexes in azide-alkyne cycloadditions.

Ruthenium-catalyzed Huisgen [3þ2] cycloaddition reaction of ynamides with various azides are performed to yield 1-protected 5- 150 Scheme 84. Synthesis of 4,5-disubstituted-1,2,3-(NH)-triazoles. amido 1,2,3-triazoles. Catalytic amount of [Cp*RuCl2]n promote 1,3-dipolar cycloaddition of trifluoromethylated propargylic M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5275 alcohols with azides to afford 4-trifluoromethyl-1,4,5- combination with different crown ethers showed that CsF with 18- trisubstituted-1,2,3-triazoles exclusively in high yields.151 Bar- crown-6 ether in 1:1 ratio in acetonitrile was found to be optimal luenga et al. employed palladium catalysts in presence of ligands conditions (Scheme 90). Larock and co-workers157b also synthe- like xantphos in the synthesis of 1H-1,2,3-triazoles from sodium sized various triazoles employing the similar strategy. Zhang and azide and alkenyl bromides. In this method instead of vinyl azide Moses158 synthesized substituted benzotriazoles 341 via click 1H-1,2,3-triazoles are formed.152a chemistry through benzyne mechanism. Wu et al. disclosed a methodology for the synthesis of 4,5- disubstituted-2H-1,2,3-triazoles 335 by the treatment of 2- alkynylbenzonitriles 333 with sodium azide in DMSO at 140 C under microwave irradiation in 60e99% yields (Scheme 88). In addition to that if 8 equiv of ZnBr2 was added with 8 equiv of so- dium azide in DMF at 100 C tetrazolo[5,1-a]isoquinolines was formed up to 87% yield.152b Microwave synthesis of C-carbamoyl- 1,2,3-triazoles by 1,3-dipolar addition has also been reported by Katritzky and co-workers.152c

Scheme 90. Synthesis of benzotriazoles via [3þ2] cycloaddition of azides with in situ generated arynes.

Numerous 1-alkyl benzotriazoles 344 were synthesized in good yields by the reaction of various alkyl azides 343 with 2-(trime- thylsilyl) phenyl triflate 342 in the presence of CsF in acetonitrile via fluoride triggered azide-benzyne cycloaddition (Scheme 91).159

Scheme 88. MW-assisted synthesis of 1,2,3-triazoles 335.

Yao and co-workers153 used nitro group of chromene moiety in click chemistry to achieve the synthesis of 4-aryl-1,4- Scheme 91. Synthesis of 1-alkyl benzotriazoles via benzyne mechanism. dihydrochromeno-[4,3-d][1,2,3]triazole derivatives 338 in DMSO at 80 C under catalyst-free conditions (Scheme 89). 160a Since the initial reports in the 1980s on the application of Ankati and Biehl synthesized functionalized benzotriazoles benzotriazole derivatives in organic synthesis,154 tremendous employing click method through benzyne mechanism. Chan- 160b progress has been achieved in this field in due course of time. Now drasekaran et al. developed a regioselective synthesis of several benzotriazole intermediates are frequently used in various organic enantiopure 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]-pyrazin-6- transformations.155 Benzotriazoles are well known as one of the ones 347 and 348 from primary amines and a-amino acid de- 161 pharmacologically significant structural motifs found in many bi- rivatives (Scheme 92). Huang and co-workers checked the con- ologically active compounds used as anti-cancer, anti-fungal, anti- trol of regioselectivity over gold nanocrystals of different surfaces inflammatory and anti-depressant agents.156 for the synthesis of 1,4-disubstituted 1,2,3-triazole through the click reaction. They used gold nanocubes, octahedra, and rhombic dodecahedra to investigate their catalytic efficiency and product regioselectivity for the azide-alkyne cycloaddition reaction for the first time. The size of the rhombic-dodecahedral gold particles was systematically tuned with high uniformity to explore the effect of size on reactivity.

Scheme 92. Regioselective synthesis of enantiopure 4,5,6,7-tetrahydro[1,2,3]triazolo Scheme 89. Synthesis of 4-aryl-1,4-dihydrochromeno[4,3-d] 1,2,3-triazoles 338. [1,5-a]-pyrazin-6-ones.

Mani and Fitzgerald162 disclosed the one-pot intramolecular 1,3-dipolar cycloaddition approach for production of triazole-fused Feringa et al.157a have reported the synthesis of benzotriazoles heterocyclic compounds 353 based on the strategy of in situ gen- 341 by the reaction of azides with arynes (generated in situ) via eration of substituted diazomethanes in a two-step sequence from [3þ2] cycloaddition. KF paired with 18-crown-6 led to full con- the corresponding aldehydes 349, which endure smooth cycload- version of starting materials to the benzotriazole at room temper- dition with a cyano group to yield the desired fused 1,2,3-triazoles ature in good yields. Screening of various fluoride salts in 353 in good overall yields (Scheme 93). 5276 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

Scheme 93. Synthesis of triazole-fused heterocycle. Scheme 96. Sc(OTf)3-catalyzed azide-alkyne cycloaddition.

4-Aryl-NH-1,2,3-triazoles 356 have been synthesized by 1,3- dipolar cycloaddition reaction of nitroolefins 354 and sodium 365, propargylic amines 366, and ammonium acetate. This process azide mediated by p-TsOH in high yields. p-TsOH was used as a vital involves tandem InCl3-catalyzed cyclocondensation and intra- additive in this type of 1,3-dipolar cycloaddition. This cycloaddition molecular azide-alkyne 1,3-dipolar cycloaddition reactions reaction tolerates a wide range of functional groups and is a reliable (Scheme 97). method for the rapid elaboration of readily available nitroolefins 163 and NaN3 into a variety of NH-1,2,3-triazoles (Scheme 94).

Scheme 94. p-TsOH-mediated synthesis of 4-aryl-NH-1,2,3-triazoles. Scheme 97. Synthesis of 9H-benzo[f]imidazo[1,2-d][1,2,3]triazolo[1,5-a][1,4] diazepines.

The 1,3-dipolar cycloadditions between substituted vinyl sul- The 1,3-dipolar cycloaddition reaction of boron azides 369 with fones 357 and sugar azide have been reported in conjunction with alkynes 370 has been investigated experimentally and computa- 167 new experimental results, and the origin of reversal of regiose- tionally by Muller et al. At room temperature pinBN3 ¼ lectivity has been revealed using a distortion/interaction model. (pin pinacolato) reacts with the strained triple bond of cyclo- This study provides the scientific justification for combining or- octyne forming an oligomeric boryl triazole 371. Alcoholysis of the ganic azides with two different types of vinyl sulfones for the oligomer yields the 4,5,6,7,8,9-hexahydro-2H-cyclooctatriazole preparation of 1,5-disubstituted 1,2,3-triazoles 359 and 1,4- 372. The oxygen-substituted azidoborane pinBN3 does not readily disubstituted triazolyl esters 360 under metal-free conditions react with oxygen atoms carrying electron-poor alkynes at room (Scheme 95).164 temperature. Only the strained cyclooctyne undergoes a smooth reaction with pinBN3 yielding an oligomeric product that can be cleaved into the expected triazole derivative by alcoholysis (Scheme 98).

Scheme 95. Synthesis of 1,5-disubstituted 1,2,3-triazoles and 1,4-disubstituted triazolyl Scheme 98. Synthesis of 4,5,6,7,8,9-hexahydro-2H-cyclooctatriazole 372. esters under metal-free conditions.

168 An efficient synthesis of annulated 9H-benzo[b]pyrrolo[1,2-g] Molteni et al. disclosed 1,3-dipolar cycloadditions of [1,2,3]-triazolo[1,5-d][1,4]diazepines 363 has been developed by MeOPEG-supported azide with a variety of dipolarophiles, and Sc(OTf)3-catalyzed two-component tandem C-2 functionalization- synthesized 1-MeOPEG supported 1,2,3-triazoles, 1,2,3,4- intramolecular azide-alkyne 1,3-dipolar cycloaddition reaction tetrazoles, and aziridine in nearly quantitative yields. Ganem and 169a (Scheme 96). The reaction shows high substrate tolerance and pro- co-workers developed multicomponent dipolar cycloaddition vides a library of fused heterocycles that may lead to novel biologically reaction for the synthesis of densely functionalized oxazoles 375 active compounds or drug lead molecules.165 and tetrazoles 377. They used acyl cyanides 373 derived from Nguyen et al.166 developed an operationally simple, one-pot modified Passerini protocol and then applied click chemistry to multicomponent reaction for the synthesis of 9H-benzo[f]imi- form complex 1,3-oxazoles or tetrazoles from diazomalonic esters dazo[1,2-d][1,2,3]triazolo[1,5-a][1,4]diazepines 368 decorated or alkyl azides, respectively (Scheme 99). 170 with three diversification points via an atom-economical trans- Schmidt et al. applied click chemistry in ionic liquids based on formation incorporating R-diketones 364, O-azidobenzaldehydes alkylated imidazoles combined with microwave heating to remove M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5277

McNulty et al. described a maiden report of synthesis of novel silver(I)acetate complex ligated to a 2-diphenylphosphino-N,N,- diisopropylcarboxamide ligand and their catalytic application on the cycloaddition of azides with terminal alkynes at room tem- perature.175 Lim et al. performed cycloaddition of azides and ter- minal alkynes in H2O in the presence of catalytic amount of b- cyclodextrin as a phase transfer catalyst to synthesize 1,4- Disubstituted-1,2,3-triazoles.176 Johansson et al. used ruthenium catalyst in azide-alkyne cy- cloaddition under microwave irradiation. They in situ generated organic azide from the primary alkyl halide and sodium azide in DMA under microwave heating followed by the addition of [RuClCp*-(PPh3)2] and the alkyne to get the desired cycloaddition product by continuing the microwave irradiation.177 Sun et al. re- ported an iridium-catalyzed intermolecular cycloaddition of azide with electron-rich internal thio-alkynes (IrAAC) which can be a complementary to the well-known CuAAC and RuAAC click re- actions (Scheme 102).178

Scheme 99. Synthesis of highly functionalized oxazoles and tetrazoles.

the hazards with volatile azides in intermolecular reactions and the problem of removal of zinc salts from the acidic product. Beccalli and co-workers171 performed totally regioselective cycloadditions of 1,3-dipoles nitrile oxide and azide with N,N-disubstituted Scheme 102. Iridium-catalyzed 1,3-DC of azides and alkynes. propargyl amines leading to the formation of polyheterocyclic systems. Zinc bromide has been used as catalyst to develop a simple route for the synthesis of Boc-protected tetrazole analogs 379 of Rao et al. developed a raney Nickel-catalyzed acetylene-azide amino acids starting from N-Boc amino acids in a [2þ3] cycload- cycloaddition reactions to form 1,2,3-triazoles. Unlike CuSO4/so- dition of Boc-a-amino nitrile 378 and sodium azide (Scheme dium ascorbate reagent system, the process does not require a re- 179 100).172 ducing agent. Chen and co-workers developed a simple and efficient synthetic method of 1,3-dipolar cycloaddition of azides with arynes generated in situ from benzobisoxadisilole or 2,3- naphthoxadisilole 390 (Scheme 103).180 The reaction was con- trolled by electronic effects. Presence of electron-withdrawing groups in the aryne moiety show high reactivity compared to that of electron-donating groups.

Scheme 100. Synthesis of Boc-protected tetrazole 379.

Charcoal impregnated with zinc can also catalyze the cycload- dition of organic azides and alkynes to provide the corresponding 1,4-disubstituted 1,2,3-triazoles and 1,4,5-trisubstituted 1,2,3- 173 triazoles. Yao et al. developed a metal-free NH4OAc-catalyzed 1,3-dipolar cycloaddition of boron-azides and nitriles leading to the Scheme 103. Cycloaddition of azides with in situ generated arynes from benzobi- synthesis of tetrazoles with broad substrate scope and in excellent soxadisilole or 2,3-naphthoxadisilole 390. yields (Scheme 101).174 5. Photoclick chemistry

In the recent decade photoclick chemistry has gained tremen- dous importance due to its wide utility in bioorthogonal chemistry, which is an important tool to visualize protein expression, track protein localization, measure protein activity, and identify protein interaction partners in living systems. The initial idea was de- veloped from the earlier reports on robust photolysis of diaryl tetrazole. Under UV-irradiation diaryl tetrazole efficiently undergo photolysis to release nitrogen. It leads to the formation of imine dipole, which spontaneously undergoes 1,3-dipolar cycloaddition with alkenes to afford pyrazoline cycloadduct 394 (Scheme Scheme 101. Metal-free NH4OAc-catalyzed 1,3-DC of boron-azides and nitriles. 104).181a 5278 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

Scheme 104. Synthesis of functionalized pyrazolines 394.

Lin et al. synthesized a series of polysubstituted pyrazolines through photoactivated 1,3-dipolar cycloaddition procedure. The reactive nitrile imine dipoles were generated in situ using a hand- held UV lamp at 302 nm followed by its spontaneous cycloaddition with a broad range of 1,3-dipolarophiles leading to the pyrazolines with excellent solvent compatibility, functional group tolerance, Scheme 107. Synthesis of pyrazolines via photoinduced 1,3-dipolar cycloaddition. regioselectivity and yield (Scheme 105).181b

Scheme 105. Synthesis of pyrazolines 397.

Later on they discovered several diaryltetrazoles which can be photoactivated in long-wavelength (around 365 nm) to be used in the 1,3-dipolar cycloaddition reactions with electron-deficient and conjugated alkenes in organic solvents as well as protein- Scheme 108. Photoinduced 1,3-dipolar cycloaddition with alkenes genetically en- coded in protein inside E. coli cells. containing alkene in the aqueous buffer (Scheme 106).182

Scheme 106. Use of diaryltetrazoles to access pyrazolines. Scheme 109. Tuning the HOMO energy of the nitrile imine dipoles.

Consequently they elaborated the photoinducible 1,3-dipolar They further continued their study on bioorthogonal reactions cycloaddition reaction for selective protein modification in bi- on E. coli by genetically incorporating a photoreactive unnatural ological media. They attached the tetrazole group to the proteins by amino acid, p-(2-tetrazole)phenylalanine (p-Tpa) into the myoglo- protein semisynthesis followed by its treatment with a simple set bin in E. coli site-specifically by evolving an orthogonal tRNA/ of alkenes leading to the pyrazoline cycloadducts. Thus fluorescent aminoacyl-tRNA synthetase pair and the use of p-Tpa as a bio- pyrazolines were used to monitor the nonfluorescent protein la- orthogonal chemical ‘handle’ for fluorescent labeling of p-Tpa- beling in cellular systems (Scheme 107).183 encoded myoglobin via photoclick reaction.186 In another concurrent report, Lin et al. used a reverse protocol to They used photoinduced 1,3-dipolar cycloaddition reaction in selectively functionalize proteins via bioorthogonal chemistry. This ‘‘stapling’’ peptide side chains to reinforce stapled peptides based time they choose alkene genetically encoded in a protein inside E. on Karle and Balaram’s heptapeptidic 310 helix model. The result- coli cells and selectively functionalize it with external tetrazoles ing pyrazoline ‘staplers’ were found to exhibit unique fluorescence using photoclick approach (Scheme 108).184 convenient for cell permeability study (Scheme 110).187 A fast photoclick reaction can be achieved either by increasing Later on, in another example they applied photoinduced 1,3- the HOMO energy of the dipole or by decreasing the LUMO energy dipolar cycloaddition reaction to ‘staple’ a peptide dual inhibitor of dipolarophile. In their study Lin group choose to further improve of the p53-Mdm2/Mdmx interactions.188 In a report Lin et al. syn- their strategy by tuning the HOMO energies of the nitrile imine thesized a series of structurally novel photoactivatable macrocyclic dipoles. In case of the tetrazole with H as R1 and 4-OMe as R2 they diphenyl tetrazoles by inserting a bridge between the two flanking could label an alkene-encoded protein inside Escherichia coli cells in diphenyl rings. Compare to the acyclic tetrazole, several macrocy- less than 1 min (Scheme 109).185 clic tetrazoles showed improved reactivity toward a strained alkene M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5279

spatially controlled imaging of microtubules in live mammalian cells via the fluorogenic, two-photon-triggered photoclick chemistry.194 In another report, they discussed the design and synthesis of strained spirocyclic alkene, spiro[2.3]hex-1-ene (Sph), to achieve an accelerated photoclick chemistry, and its site-specific in- troduction into proteins via amber codon suppression using the wild type pyrrolysyl-tRNA synthetase/tRNACUA pair.195 Schnarr et al. developed a photoinduced, benzyne click reaction leading to a wide range of benzotriazole derivatives (Scheme 112).196 Scheme 110. Photoinduced 1,3-dipolar cycloaddition in stapling peptide side chains. in organic solvent thus making them suitable for the bioorthogonal tetrazoleealkene cycloaddition reaction in living systems.189 They also introduced a series of photoactivatable diary- ltetrazoles for photoclick chemistry via ‘scaffold hopping’ strat- egy.190 In another report they discussed the design of terthiophene- based photoactivatible tetrazoles. The new class of tetrazoles get activated in 405 nm light and subsequently reacts with fumarate dipolarophile with the second-order rate constant with k2 ex- ceeding 103 M 1 s 1. They also demonstrated the utility of this Scheme 112. Photoinduced benzyne click reaction leading to benzotriazoles 423. laser-activatable tetrazole in imaging microtubules in a spatiotem- porally controlled manner in live cells (Scheme 111).191 6. Advances of click methods in chemical biology

The generation of active Cu(I) catalyst in click reaction suffers from two major drawbacks to be widely used in bioorthogonal reactions. One is the cytotoxicity of Cu(I), which limits the utility of click reaction in living cells. Second one is the slow reaction rate, which hampers the quantitative tagging of biomolecules. There- fore, several modifications were made with respect to catalytic system and ligands to make click method more biocompatible to increase its usage in bioorthogonal reactions and chemical biology. Wu et al. introduced BTTES 1, a tris(triazolylmethyl)amine- based ligand for Cu(I) that coordinates with copper during the process leading to the rapid click reaction in living systems without apparent toxicity. With the catalytic system they did the non- invasive imaging of fucosylated glycans during zebrafish early embryogenesis (Fig. 4).197

Scheme 111. Design and utility of terthiophene-based photoactivatable tetrazoles.

A new class of bithiophene-substituted tetrazoles with ex- tended p-systems were designed and synthesized which gets ac- tivated upon 405 nm laser light irradiation to undergo fast 1,3- Fig. 4. Tris(triazolylmethyl)amine-based Cu(I) complex. dipolar cycloaddition reactions with dimethyl fumarate with sec- ond order rate constants. The pyrazoline cycloadducts thus formed exhibited solvent-dependent red fluorescence; making them po- In another report, they evaluated the efficacy of bioorthogonal tentially useful as fluorogenic probes for in vivo detection of al- reactions for bioconjugation in four different biological settings. kenes.192 In a new strategy, they applied intramolecular tetrazole- With their newly developed biocompatible ligands BTTAA, BTTES, alkene cycloaddition reaction to generate turn-on pyrazoline fluo- TBTA and THPTA they achieved an unsurpassed bioconjugation rophore in situ.193 efficiency in copper-catalyzed azideealkyne cycloaddition which is They further applied photoclick chemistry to living organisms quite promising to be a highly potent and adaptive tool for with improved spatiotemporal control by using water-soluble, cell- a broader spectrum of biological applications (Fig. 5).198 permeable naphthalene-based tetrazoles. This kind of tetrazoles In a consecutive report they performed a structureeactivity were efficiently activated by two-photon excitation with 700 nm relationship study through which they identified another new femtosecond pulsed laser to generate the active dipole leading to tris(triazolylmethyl)amine-based ligand (BTTPS) that shows better the desired cycloaddition. Thus it can be used for real-time, kinetics to accelerate the CuAAC.199 With a combination of 5280 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

click method for various purposes. Favorable conditions to carry out the CuAAC-OS open up new avenues to tackle future synthetic challenges.

Acknowledgements

We sincerely acknowledge the many colleagues and friends in particular to Prof. H. Ila, JNCASR, Bangalore for their valuable sug- gestions and helpful discussions. We are grateful to University Grants Commission (F.19-154/2015(BSR)), Council of Scientific and Industrial Research (02(0072)/12/EMR-II), Science and Engineering Research Board (SB/S1/OC-30/2013) and Department of Science & Technology (SR/S1/OC-66/2009) (New Delhi) for funding to our research projects at various times. Finally, we thank to students who have contributed so much in terms of ideas and effort to our research programs over many years and truly made the journey worthwhile.

References and notes

Fig. 5. Biocompatible ligands BTTAA, BTTES, TBTA and THPTA. 1. (a) Uttamchandani, M.; Lu, C. H. S.; Yao, S. Q. Acc. Chem. Res. 2009, 42, 1183e1192; (b) Kolb, H. C.; Sharpless, K. B. Drug Discov. Today 2003, 8, 1128e1137; (c) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40,2004e2021; (d) Lutz, J.-F.; Zarafshani, Z. Adv. Drug Delivery Rev. 2008, electron-donating picolyl azide and BTTPS they detected newly 60, 958e970. synthesized cell-surface glycans by flow cytometry using only 1 nM 2. (a) Buckle, D. R.; Rockell, C. J. M. J. Chem. Soc., Perkin Trans. 1 1982,627e630; (b) of a metabolic precursor. They used the supersensitive chemistry to Buckle, D. R.; Outred, D. J.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. J. Med. Chem. 1983, 26,251e254; (c) Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. J. monitor the dynamic glycan biosynthesis in mammalian cells and Med. Chem. 1986, 29, 2267e2269. 200 in early zebrafish embryogenesis (Fig. 6). 3. (a) Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn, M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega, K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. J. Med. Chem. 2000, 43, 953e970; (b) Alvarez, R.; Ve- lazquez, S.; SaneFelix, A.; Aquaro, S.; De Clercq, E.; Perno, C.-F.; Karlsson, A.; Balzarini, J.; Camarasa, M. J. J. Med. Chem. 1994, 37,4185e4194; (c) Tiwari, V. K.; Mishra, B. B.; Mishra, K. B.; Mishra, N.; Singh, A. S.; Chen, X. Chem. Rev. 2016, 116, 3086e3240; (d) Totobenazara, J.; Burke, A. J. Tetrahedron Lett. 2015, 56, 2853e2859; (e) Castro, V.; Rodríguez, H.; Albericio, F. ACS Comb. Sci. 2016, 18,1e14. 4. Singh, M. S.; Chowdhury, S.; Koley, S. Tetrahedron 2016, 72, 1603e1644. 5. (a) Bock, V. D.; Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem. 2006, 51e68; (b) Liang, L.; Astruc, D. Coord. Chem. Rev. 2011, 255, 2933e2945. 6. (a) Zhang, L.; Chen, X.; Xue, P.; Sun, H. H. Y.; Williams, I. D.; Sharpless, K. B.; Fokin, V. V.; Jia, G. J. Am. Chem. Soc. 2005, 127, 15998e15999. 7. Wamhoff, H. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984; Vol. 5, pp 669e732. 8. Jiang, Y.; Kuang, C.; Yang, Q. Synlett 2009,3163e3166. 9. (a) Gonda, Z.; Lorincz, K.; Novak, Z. Tetrahedron Lett. 2010, 51,6275e6277. Fig. 6. BTTPS to detect newly synthesized cell-surface glycans. 10. Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A.; Quarta, M. R.; Fittipaldi, M. Synthesis 2009, 3853e3859. 11. Lorincz,} K.; Kele, P.; Novak, Z. Synthesis 2009, 3527e3532. 12. Cuevas, F.; Oliva, A. I.; Pericas, M. A. Synlett 2010, 1873e1877. 7. Summary and outlook 13. Zhao, Y.-B.; Yan, Z.-Y.; Liang, Y.-M. Tetrahedron Lett. 2006, 47, 1545e1549. 14. Hagiwara, H.; Sasaki, H.; Hoshi, T.; Suzuki, T. Synlett 2009, 643e647. CuAAC has made a significant contribution to click chemistry 15. Vecchi, A.; Chambery, A.; Chiappe, C.; Marra, A.; Dondoni, A. Synthesis 2010, 2043e2048. and reveals the potential of this kind of click reaction for the rapid 16. (a) Louerat, F.; Bougrin, K.; Loupy, A.; Retana, A. M. O.; Pagalday, J.; Palacios, F. construction of several useful molecules. The impact of click Heterocycles 1998, 48,161e170; (b) Savin, K. A.; Robertson, M.; Gerneret, D.; chemistry is increasing tremendously day by day not only in the Green, S.; Hembre, E. J.; Bishop, J. Mol. Div. 2003, 7,171e174; (c) Ermolat’ev, D.; e fi Dehaen, W.; Van der Eycken, E. QSAR Comb. Sci. 2004, 23,915 918; (d) eld of organic synthesis, but also in drug discovery efforts, poly- Guezguez, R.; Bougrin, K.; El Akri, K.; Benhida, R. Tetrahedron Lett. 2006, 47, mer chemistry and in different disciplines of material science. Not 4807e4811. only it serves the academia but also is employed extensively in the 17. Sreedhar, B.; Surendra Reddy, P. Synth. Commun. 2007, 37, 805e812. e fi 18. Li, J.; Wang, D.; Zhang, Y.; Li, J.; Chen, B. Org. Lett. 2009, 11, 3024 3027. practical elds such as in the preparation of glycoconjugates, potent 19. Tasdelen, M. A.; Yagci, Y. Angew. Chem., Int. Ed. 2013, 52, 5930e5938. glycosidase inhibitors, and even protein and DNA modifications. 20. Tasdelen, M. A.; Yagci, Y. Tetrahedron Lett. 2010, 51, 6945e6947. The future portends even greater and richer implementations of 21. Sirion, U.; Bae, Y. J.; Lee, B. S.; Chi, D. Y. Synlett 2008, 2326e2330. 22. Kumar, D.; Reddy, V. B. Synthesis 2010, 1687e1691. this strategic tool to a vast range of other synthetic and material 23. Jlalia, I.; Elamari, H.; Meganem, F.; Herscovici, J.; Girard, C. Tetrahedron Lett. science applications. Click chemistry accelerates both lead finding 2008, 49, 6756e6758. and lead optimization due to its greater scope, modular design and 24. Zhang, X.; Yang, X.; Zhang, S. Synth. Commun. 2009, 39, 830e844. € d reliance on extremely short sequences of near-perfect reactions. 25. Richters, T.; Krug, O.; Kcsters, J.; Hepp, A.; Muller, J. Chem. Eur. J. 2014, 20, 7811e7818. Herein, the emerging methodologies employing click chemistry 26. (a) Dellisola, A.; McLachlan, M. M. W.; Neuman, B. W.; Al-Mullah, H. M. N.; with a brief description of each has been presented in a best pos- Binks, A. W. D.; Elvidge, W.; Shankland, K.; Cobb, A. J. A. Chem.dEur. J. 2014, 20, 11685e11689; (b) Moustafa, A. H.; El-Sayed, H. A.; Haikal, A. Z.; El Ashry, E. sible mode with the hope that this review would satisfy the e fi S. H. Nucleosides Nucleotides Nucleic Acids 2011, 30, 340 352. workers involved directly or indirectly to the elds, which employ 27. Anand, N.; Jaiswal, N.; Pandey, S. K.; Srivastava, A. K.; Tripathi, R. P. Carbohydr. Res. 2011, 346,16e25. M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5281

28. (a) Krim, J.; Sillahi, B.; Taourirte, M.; Rakib, E. M.; Engels, J. W. Arkivoc 2009, 81. Suarez, P. L.; Gandara, Z.; Gomez, G.; Fall, Y. Tetrahedron Lett. 2004, 45, xiii,142e152; (b) Broggi, J.; Kumamoto, H.; BerteinaeRaboin, S.; Nolan, S. P.; 4619e4621. Agrofoglio, L. A. Eur. J. Org. Chem. 2009, 1880e1888. 82. Chittaboina, S.; Xie, F.; Wang, Q. Tetrahedron Lett. 2005, 46,2331e2336. 29. Malnuit, V.; Duca, M.; Manout, A.; Bougrin, K.; Benhida, R. Synlett 2009, 83. Broggi, J.; Joubert, N.; DíezeGonzalez, S.; BerteinaeRaboin, S.; Zevaco, T.; 2123e2128. Nolan, S. P.; Agrofoglio, L. A. Tetrahedron 2009, 65,1162e1170. 30. Lucas, R.; Neto, V.; Bouazza, A. H.; Zerrouki, R.; Granet, R.; Krausz, P.; Cham- 84. Brunet, E.; Juanes, O.; Jimenez, L.; Rodríguez-Ubis, J. C. Tetrahedron Lett. 2009, pavier, Y. Tetrahedron Lett. 2008, 49,1004e1007. 50, 5361e5363. 31. Yan, Z.-Y.; Zhao, Y.-B.; Fan, M.-J.; Liu, W.-M.; Liang, Y.-M. Tetrahedron 2005, 61, 85. Qvortrup, K.; Petersen, M. A.; Hassenkam, T.; Nielsen, M. B. Tetrahedron Lett. 9331e9337. 2009, 50,5613e5616. 32. Yang, D.; Fu, N.; Liu, Z.; Li, Y.; Chen, B. Synlett 2007,278e282. 86. Montagnat, O. D.; Lessene, G.; Hughes, A. B. Tetrahedron Lett. 2006, 47, 33. Luvino, D.; Amalric, C.; Smietana, M.; Vasseur, J.-J. Synlett 2007, 3037e3041. 6971e6974. 34. do Nascimento, W. S.; Camara, C. A.; de Oliveira, R. N. Synthesis 2011, 87. Detz, R. J.; Heras, S. A.; de Gelder, R.; van Leeuwen, P. W. N. M.; Hiemstra, H.; 3220e3224. Reek, J. N. H.; Maarseveen, J. H. Org. Lett. 2006, 8, 3227e3230. 35. Xu, M.; Kuang, C.; Wang, Z.; Yang, Q.; Jiang, Y. Synthesis 2011, 223e228. 88. Vallee, M. R. J.; Artner, L. M.; Dernedde, J.; Hackenberger, C. P. R. Angew. Chem., 36. Nguyen, D. M.; Miles, D. H. Synth. Commun. 2011, 41, 1759e1771. Int. Ed. 2013, 52, 9504e9508. 37. Klein, M.; Diner, P.; Dorin-Semblat, D.; Doerig, C.; Grøtli, M. Org. Biomol. Chem. 89. Ye, C.; Gard, G. L.; Winter, R. W.; Syvret, R. G.; Twamley, B.; Shreeve, J. M. Org. 2009, 7, 3421e3429. Lett. 2007, 9, 3841e3844. 38. Cheng, X.; Yang, Y.; Kuang, C.; Yang, Q. Synthesis 2011, 2907e2912. 90. Huang, Y.; Gard, G. L.; Shreeve, J. M. Tetrahedron Lett. 2010, 51, 6951e6954. 39. Jiang, Y.; Kuang, C.; Yang, Q. Synthesis 2010, 4256e4260. 91. Pore, V. S.; Aher, N. G.; Kumar, M.; Shukla, P. K. Tetrahedron 2006, 62, 40. Li, L.; Li, R.; Zhu, A.; Zhang, G.; Zhang, L. Synlett 2011,874e878. 11178e11186. 41. (a) Ueda, S.; Nagasawa, H. J. Am. Chem. Soc. 2009, 131, 15080e15081. 92. Moore, E.; McInnes, S. J.; Vogt, A.; Voelcker, N. H. Tetrahedron Lett. 2011, 52, 42. Pirali, T.; Tron, G. C.; Zhu, J. Org. Lett. 2006, 8,4145e4148. 2327e2329. 43. Choi, K. W.; Brimble, M. A. Org. Biomol. Chem. 2008, 6,3518e3526. 93. Maisonneuve, S.; Xie, J. Synlett 2009,2977e2981. 44. Conte, G.; Cristiano, R.; Ely, F.; Gallardo, H. Synth. Commun. 2006, 36,951e958. 94. Bahulayan, D.; Arun, S. Tetrahedron Lett. 2012, 53, 2850e2855. 45. Ackermann, L.; Potukuchi, H. K.; Landsberg, D.; Vicente, R. Org. Lett. 2008, 10, 95. Moorhouse, A. D.; Moses, J. E. Synlett 2008, 2089e2092. 3081e3084. 96. Fletcher, J. T.; Keeney, M. E.; Walz, S. E. Synthesis 2010, 3339e3345. 46. White, J. R.; Price, G. J.; Schiffers, S.; Raithby, P. R.; Plucinski, P. K.; Frost, C. G. 97. (a) Schramm, H.; Saak, W.; Hoenke, C.; Christoffers, J. Eur. J. Org. Chem. 2010, Tetrahedron Lett. 2010, 51,3913e3917. 1745e1753; (b) Shao, C.; Wang, X.; Xu, J.; Zhao, J.; Zhang, Q.; Hu, Y. J. Org. Chem. 47. Riva, R.; Chafaqi, L.; Jer ome,^ R.; Lecomte, P. Arkivoc 2007, x, 292e306. 2010, 75,7002e7005. 48. (a) Chowdhury, C.; Mandal, S. B.; Achari, B. Tetrahedron Lett. 2005, 46, 98. Kristafor, S.; Bistrovic, A.; Plavec, J.; Makuc, D.; Martinovic, T.; Pavelic, S. K.; 8531e8534. Raic-Malic, S. Tetrahedron Lett. 2015, 56, 1222e1228. 49. Smith, N. W.; Polenz, B. P.; Johnson, S. B.; Dzyuba, S. V. Tetrahedron Lett. 2010, 99. Constant, C.; Albert, S.; Zivic, N.; Baczko, K.; Fensterbank, H.; Allard, E. Tetra- 51, 550e553. hedron 2014, 70, 3023e3029. 50. Li, P.; Wang, L.; Zhang, Y. Tetrahedron 2008, 64, 10825e10830. 100. Deobald, A. M.; Camargo, L. R. S.; Horner,€ M.; Rodrigues, O. E. D.; Alves, D.; 51. Rathwell, K.; Sperry, J.; Brimble, M. A. Tetrahedron 2010, 66,4002e4009. Braga, A. L. Synthesis 2011, 2397e2406. 52. Sai Sudhir, V.; Phani Kumar, N. Y.; Chandrasekaran, S. Tetrahedron 2010, 66, 101. Reddy, K. R.; Maheswari, C. U.; Rajgopal, K.; Kantam, M. L. Synth. Commun. 1327e1334. 2008, 38,2158e2167. 53. Qian, W.; Winternheimer, D.; Allen, J. Org. Lett. 2011, 13, 1682e1685. 102. Attanasi, O. A.; Favi, G.; Filippone, P.; Mantellini, F.; Moscatelli, G.; Perrulli, F. R. 54. Pericherla, K.; Jha, A.; Khungar, B.; Kumar, A. Org. Lett. 2013, 15, 4304e4307. Org. Lett. 2010, 12, 468e471. 55. Shao, C.; Wang, X.; Zhang, Q.; Luo, S.; Zhao, J.; Hu, Y. J. Org. Chem. 2011, 76, 103. IJsselstijn, M.; Cintrat, J.-C. Tetrahedron 2006, 62, 3837e3842. 6832e6836. 104. Bonnamour, J.; Legros, J.; Crousse, B.; BonneteDelpon, D. Tetrahedron Lett. 56. Selvarajua, M.; Sun, C.-M. Adv. Synth. Catal. 2014, 356, 1329e1336. 2007, 48, 8360e8362. 57. Zhang, Z.; Zhou, Q.; Ye, F.; Xia, Y.; Wu, G.; Hossain, M. L.; Zhang, Y.; Wang, J. 105. Seus, N.; Saraiva, M. T.; Alberto, E. E.; Savegnago, L.; Alves, D. Tetrahedron 2012, Adv. Synth. Catal. 2015, 357,2277e2286. 68, 10419e10425. 58. (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., 106. Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A.; Capuzzolo, F. Tetrahedron Int. Ed. 2002, 41, 2596e2599; (b) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. 2009, 65,10573e10580. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 107. Reddy, K. R.; Rajgopal, K.; Kantam, M. L. Synlett 2006,957e959. 210e216; (c) Sivakumar, K.; Xie, F.; Cash, B. M.; Long, S.; Barnhill, H. N.; Wang, 108. Zhang, Q.; Wang, X.; Cheng, C.; Zhu, R.; Liu, N.; Hu, Y. Org. Biomol. Chem. 2012, Q. Org. Lett. 2004, 6, 4603e4606. 10, 2847e2854. 59. Barral, K.; Moorhouse, A. D.; Moses, J. E. Org. Lett. 2007, 9, 1809e1811. 109. Quan, Z.-J.; Xu, Q.; Ma, X.; Zhang, Z.; Da, Y.-X.; Wang, X.-C. Tetrahedron 2013, 60. Beckmann, H. S. G.; Wittmann, V. Org. Lett. 2007, 9,1e4. 69, 881e887. 61. Kumar, D.; Reddy, V. B.; Kumar, A.; Mandal, D.; Tiwari, R.; Parang, K. Bioorg. 110. Chattopadhyay, B.; Rivera Vera, C. I.; Chuprakov, S.; Gevorgyan, V. Org. Lett. Med. Chem. Lett. 2011, 21,449e452. 2010, 12,2166e2169. 62. Kategaonkar, A. H.; Shinde, P. V.; Kategaonkar, A. H.; Pasale, S. K.; Shingate, B. 111. Yadav, J. S.; Subba Reddy, B. V.; Chary, D. N.; Reddy, C. S. Tetrahedron Lett. 2008, B.; Shingare, M. S. Eur. J. Med. Chem. 2010, 45,3142e3146. 49,2649e2652. 63. Castagnolo, D.; Dessí, F.; Radi, M.; Botta, M. Tetrahedron: Asymmetry 2007, 18, 112. Yadav, J. S.; Subba Reddy, B. V.; Madhusudhan Reddy, G.; Anjum, S. R. Tetra- 1345e1350. hedron Lett. 2009, 50, 6029e6031. 64. DelaineBioton, L.; Villemin, D.; Lohier, J.-F.; Sopkova, J.; Jaffres, P.-A. Tetrahe- 113. Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.; Giorgi, G.; Mantellini, dron 2007, 63,9677e9684. F.; Perrulli, F. R.; Spinelli, D. Tetrahedron 2008, 64, 3837e3858. 65. Artyushin, O. I.; Osipov, S. N.; Roschenthaler,€ G.-V.; Odinets, I. L. Synthesis 114. Fukuzawa, S.; Shimizu, E.; Kikuchi, S. Synlett 2007, 2436e2438. 2009,3579e3588. 115. (a) Candelon, N.; Lastecoueres, D.; Diallo, A. K.; Aranzaes, J. R.; Astruc, D.; 66. Kolarovic, A.; Schnurch, M.; Mihovilovic, M. D. J. Org. Chem. 2011, 76, Vincent, J.-M. Chem. Commun. 2008,741e743; (b) Lipshutz, B. H.; Taft, B. R. 2613e2618. Angew. Chem., Int. Ed. 2006, 45, 8235e8238. 67. Yap, A. H.; Weinreb, S. M. Tetrahedron Lett. 2006, 47, 3035e3038. 116. Sau, S. C.; Raha Roy, S.; Sen, T. K.; Mullangi, D.; Mandal, S. K. Adv. Synth. Catal. 68. Dururgkar, K. A.; Gonnade, R. G.; Ramana, C. V. Tetrahedron 2009, 65, 2013, 355, 2982e2991. 3974e3979. 117. Park, J. C.; Kim, Y.; Kim, J. Y.; Park, S.; Park, K. H.; Song, H. Chem. Commun. 2012, 69. Appukkuttan, P.; Dehaen, W.; Fokin, V. V.; Van der Eycken, E. Org. Lett. 2004, 6, 8484e8486. 4223e4225. 118. Wang, D.; Zhao, M.; Liu, X.; Chen, Y.; Lia, N.; Chen, B. Org. Biomol. Chem. 2012, 70. Chandrasekhar, S.; Basu, D.; Rambabu, Ch Tetrahedron Lett. 2006, 47, 10, 229e231. 3059e3063. 119. Berg, R.; Straub, J.; Schreiner, E.; Mader, S.; Rominger, F.; Straub, B. F. Adv. Synth. 71. Urankar, D.; Steinbucher, M.; Kosjek, J.; Kosmrlj, J. Tetrahedron 2010, 66, Catal. 2012, 354,3445e3450. 2602e2613. 120. Pierangelo Fabbrizzi, P.; Cicchi, S.; Brandi, A.; Sperotto, E.; van Koten, G. Eur. J. 72. Aizpurua, J. M.; Azcune, I.; Fratila, R. M.; Balentova, E.; SagartzazueAizpurua, Org. Chem. 2009, 5423e5430. M.; Miranda, J. I. Org. Lett. 2010, 12, 1584e1587. 121. Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. J. Org. Chem. 2011, 76, 8394e8405. 73. Ladouceur, S.; Soliman, A. M.; ZysmaneColman, E. Synthesis 2011, 122. Kumar, B. S. P. A.; Reddy, K. H. V.; Madhav, B.; Ramesh, K.; Nageswar, Y. V. D. 3604e3611. Tetrahedron Lett. 2012, 53, 4595e4599. 74. Doak, B. C.; Scanlon, M. J.; Simpson, J. S. Org. Lett. 2011, 13,537e539. 123. Nakamura, T.; Terashima, T.; Ogata, K.; Fukuzawa, S. Org. Lett. 2011, 13, 75. Fletcher, J. T.; Walz, S. E.; Keeney, M. E. Tetrahedron Lett. 2008, 49, 7030e7032. 620e623. 76. Hu, M.; Li, J.; Yao, S. Q. Org. Lett. 2008, 10, 5529e5531. 124. (a) Orgueira, H. A.; Fokas, D.; Isome, Y.; Chan, P. C.-M.; Baldino, C. M. Tetra- 77. Valverde, I. E.; Delmas, A. F.; Aucagne, V. Tetrahedron 2009, 65, 7597e7602. hedron Lett. 2005, 46,2911e2914; (b) Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, 78. Naveen; Babu, S. A.; Aslam, N. A.; Sandhu, A.; Singh, D. A.; Rana, A. Tetrahedron M. Eur. J. Org. Chem. 2010, 1875e1884. 2015, 71, 7026e7045. 125. (a) Yadav, J. S.; Subba Reddy, B. V.; Madhusudhan Reddy, G.; Chary, D. N. 79. Spivak, A. Y.; Gubaidullin, R. R.; Galimshina, Z. R.; Nedopekina, D. A.; Odino- Tetrahedron Lett. 2007, 48, 8773e8776; (b) Liu, M.; Reiser, O. Org. Lett. 2011, 13, kov, V. N. Tetrahedron 2016, 72, 1249e1256. 1102e1105. 80. Song, S.-X.; Zhang, H.-L.; Kim, C.-G.; Sheng, L.; He, X.-P.; Long, Y.-T.; Li, J.; Chen, 126. Lipshutz, B. H.; Nihan, D. M.; Vinogradova, E.; Taft, B. R.; Boskovic, Z. V. Org. G.-R. Tetrahedron 2010, 66,9974e9980. Lett. 2008, 10,4279e4282. 5282 M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283

127. (a) Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. Tetrahedron Lett. 2009, 50, 157. (a) CampbelleVerduyn, L.; Elsinga, P. H.; Mirfeizi, L.; Dierckx, R. A.; Feringa, B. 2358e2362; (b) Teyssot, M.-L.; Nauton, L.; Canet, J.-L.; Cisnetti, F.; Chevry, A.; L. Org. Biomol. Chem. 2008, 6, 3461e3463; (b) Shi, F.; Waldo, J. P.; Chen, Y.; Gautier, A. Eur. J. Org. Chem. 2010, 3507e3515; (c) Kamijo, S.; Jin, T.; Huo, Z.; Larock, R. C. Org. Lett. 2008, 10,2409e2412. Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 7786e7787; (d) Friscourt, F.; Boons, 158. Zhang, F.; Moses, J. E. Org. Lett. 2009, 11, 1587e1590. G.-J. Org. Lett. 2010, 12, 4936e4939; (e) Park, I. S.; Kwon, M. S.; Kim, Y.; Lee, J. 159. Chandrasekhar, S.; Seenaiah, M.; Rao, C. L.; Reddy, C. R. Tetrahedron 2008, 64, S.; Park, J. Org. Lett. 2008, 10, 497e500. 11325e11327. 128. Wei, F.; Li, H.; Song, C.; Ma, Y.; Zhou, L.; Tung, C.-H.; Xu, Z. Org. Lett. 2015, 17, 160. (a) Ankati, H.; Biehl, E. Tetrahedron Lett. 2009, 50, 4677e4682; (b) Sudhir, V. S.; 2860e2863. Baig, R. B. N.; Chandrasekaran, S. Eur. J. Org. Chem. 2008, 2423e2429. 129. Zhang, Z.; Dong, C.; Yang, C.; Hu, D.; Long, J.; Wang, L.; Li, H.; Chen, Y.; Kong, D. 161. Rej, S.; Chanda, K.; Chiu, C.-Y.; Huang, M. H. Chem.dEur. J. 2014, 20, Adv. Synth. Catal. 2010, 352, 1600e1604. 15991e15997. 130. Lee, C.-T.; Huang, S.; Lipshutz, B. H. Adv. Synth. Catal. 2009, 351,3139e3142. 162. Mani, N. S.; Fitzgerald, A. E. J. Org. Chem. 2014, 79, 8889e8894. 131. Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. Org. Biomol. Chem. 2011, 9, 163. Quan, X.-J.; Ren, Z.-H.; Wang, Y.-Y.; Guan, Z. H. Org. Lett. 2014, 16,5728e5731. 6385e6395. 164. Sahu, D.; Dey, S.; Pathak, T.; Ganguly, B. Org. Lett. 2014, 16,2100e2103. 132. Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. Adv. Synth. Catal. 2010, 352, 165. Hussain, M. K.; Ansari, M. I.; Kant, R.; Hajela, K. Org. Lett. 2014, 16, 560e563. 3208e3214. 166. Nguyen, H. H.; Palazzo, T. A.; Kurth, M. J. Org. Lett. 2013, 15, 4492e4495. 133. Megia-Fernandez, A.; Ortega-MuC¸ oz, M.; Hernandez-Mateo, F.; Santoyo- 167. Muller,€ M.; Mossmer,€ C. M.; Bettinger, H. F. J. Org. Chem. 2014, 79,5478e5483. Gonzaleza, F. Adv. Synth. Catal. 2012, 354, 1797e1803. 168. Molteni, G.; Buttero, P. D. Tetrahedron 2005, 61, 4983e4987. 134. Wang, B.; Liu, N.; Chen, W.; Huang, D.; Wang, X.; Hu, Y. Adv. Synth. Catal. 2015, 169. (a) Clemencon, I. F.; Ganem, B. Tetrahedron 2007, 63, 8665e8669; (b) Vaidya, 357,401e407. V. V.; Wankhede, K. S.; Nara, S. J.; Salunkhe, M. M.; Trivedi, G. K. Synth. 135. Wang, Y.; Liu, J.; Xia, C. Adv. Synth. Catal. 2011, 353, 1534e1542. Commun. 2009, 39, 3856e3866. 136. Iniyavan, P.; Balaji, G. L.; Sarveswari, S.; Vijayakumar, V. Tetrahedron Lett. 2015, 170. Schmidt, B.; Meid, D.; Kieser, D. Tetrahedron 2007, 63, 492e496. 56,5002e5009. 171. Basolo, L.; Beccalli, E. M.; Borsini, E.; Broggini, G.; Pellegrino, S. Tetrahedron 137. Tale, R. H.; Gopula, V. B.; Toradmal, G. K. Tetrahedron Lett. 2015, 56, 2008, 64,8182e8187. 5864e5869. 172. Sureshbabu, V. V.; Naik, S. A.; Nagendra, G. Synth. Commun. 2009, 39, 138. Lal, S.; Díez-Gonzalez, S. J. Org. Chem. 2011, 76, 2367e2373. 395e406. 139. Dadashi-Silab, S.; Yagci, Y. Tetrahedron Lett. 2015, 56,6440e6443. 173. Meng, X.; Xu, X.; Gao, T.; Chen, B. Eur. J. Org. Chem. 2010, 5409e5414. 140. Jin, T.; Yan, M.; Menggenbateer; Minato, T.; Bao, M.; Yamamoto, Y. Adv. Synth. 174. Yao, Y.-W.; Zhou, Y.; Lin, B.-P.; Yao, C. Tetrahedron Lett. 2013, 54,6779e6781. Catal. 2011, 353, 3095e3100. 175. McNulty, J.; Keskar, K.; Vemula, R. Chem.dEur. J. 2011, 17,14727e14730. 141. Ji, P.; Atherton, J. H.; Page, M. I. Org. Biomol. Chem. 2012, 10, 7965e7969. 176. Shin, J.-A.; Lim, Y.-G.; Lee, K.-H. J. Org. Chem. 2012, 77,4117e4122. 142. Ozkal, E.; Llanes, P.; Bravo, F.; Ferrali, A.; Pericas, M. A. Adv. Synth. Catal. 2014, 177. Johansson, J. R.; Lincoln, P.; Norden, B.; Kann, N. J. Org. Chem. 2011, 76, 356,857e869. 2355e2359. 143. Fabbrizzi, P.; Bianchini, F.; Menchi, G.; Raspanti, S.; Guarna, A.; Trabocchi, A. 178. Ding, S.; Jia, G.; Sun, J. Angew. Chem., Int. Ed. 2014, 53, 1877e1880. Tetrahedron 2014, 70, 5439e5449. 179. Rao, H. S. P.; Chakibanda, G. RSC Adv. 2014, 4, 46040e46048. 144. Pokhodylo, N. T.; Matiychuk, V. S.; Obushak, M. D. Synth. Commun. 2010, 40, 180. Lin, Y.; Chen, Y.; Ma, X.; Xu, D.; Cao, W.; Chen, J. Tetrahedron 2011, 67, 856e859. 1932e1938. 181. (a) Ramil, C. P.; Lin, Q. Curr. Opin. Chem. Biol. 2014, 21,89e95; (b) Wang, Y.; 145. Wu, L.; Chen, X.; Tang, M.; Song, X.; Chen, G.; Song, X.; Lin, Q. Synlett 2012, Rivera Vera, C. I.; Lin, Q. Org. Lett. 2007, 9,4155e4158. 1529e1533. 182. Wang, Y.; Hu, W. J.; Song, W.; Lim, R. K. V.; Lin, Q. Org. Lett. 2008, 10, 146. (a) Sengupta, S.; Duan, H.; Lu, W.; Petersen, J. L.; Shi, X. Org. Lett. 2008, 10, 3725e3728. 1493e1496; (b) Amantini, D.; Fringuelli, F.; Piermatti, O.; Pizzo, F.; Zunino, E.; 183. Song, W.; Wang, Y.; Qu, J.; Madden, M. M.; Lin, Q. Angew. Chem., Int. Ed. 2008, Vaccaro, L. J. Org. Chem. 2005, 70, 6526e6529. 47, 2832e2835. 147. Oliva, A. I.; Christmann, U.; Font, D.; Cuevas, F.; Ballester, P.; Buschmann, H.; 184. Song, W.; Wang, Y.; Qu, J.; Lin, Q. J. Am. Chem. Soc. 2008, 130, 9654e9655. Torrens, A.; Yenes, S.; Pericas, M. A. Org. Lett. 2008, 10,1617e1619. 185. Wang, Y.; Song, W.; Hu, W. J.; Lin, Q. Angew. Chem., Int. Ed. 2009, 48, 148. (a) Oliva, C. G.; Jagerovic, N.; Goya, P.; Alkorta, I.; Elguero, J.; Cuberes, R.; 5330e5333. Dordal, A. Arkivoc 2010, ii,127e147; (b) Kwok, S. W.; Fotsing, J. R.; Fraser, R. J.; 186. Wang, J.; Zhang, W.; Song, W.; Wang, Y.; Yu, Z.; Li, J.; Wu, M.; Wang, L.; Zang, J.; Rodionov, V. O.; Fokin, V. V. Org. Lett. 2010, 12,4217e4219. Lin, Q. J. Am. Chem. Soc. 2010, 132, 14812e14818. 149. (a) Boren, B. C.; Narayan, S.; Rasmussen, L. K.; Zhang, L.; Haitao Zhao, H.; Lin, 187. Madden, M. M.; Vera, C. I. R.; Song, W.; Lin, Q. Chem. Commun. 2009, Z.; Jia, G.; Fokin, V. V. J. Am. Chem. Soc. 2008, 130, 8923e8930; (b) Takasu, K.; 5588e5590. Azuma, T.; Takemoto, Y. Tetrahedron Lett. 2010, 51,2737e2740. 188. Madden, M. M.; Muppidi, A.; Li, Z.; Li, X.; Chen, J.; Lin, Q. Bioorg. Med. Chem. 150. Oppilliart, S.; Mousseau, G.; Zhang, L.; Jia, G.; Thuery, P.; Rousseau, B.; Cintrat, Lett. 2011, 21,1472e1475. J.-C. Tetrahedron 2007, 63, 8094e8098. 189. Yu, Z.; Lim, R. K. V.; Lin, Q. Chem.dEur. J. 2010, 16, 13325e13329. 151. Zhang, C.-T.; Zhang, X.; Qing, F.-L. Tetrahedron Lett. 2008, 49, 3927e3930. 190. Yu, Z.; Ho, L. Y.; Wang, Z.; Lin, Q. Bioorg. Med. Chem. Lett. 2011, 21, 5033e5036. 152. (a) Barluenga, J.; Valdes, C.; Beltran, G.; Escribano, M.; Aznar, F. Angew. Chem., 191. An, P.; Yu, Z.; Lin, Q. Chem. Commun. 2013, 9920e9922. Int. Ed. 2006, 45, 6893e6896; (b) Tsai, C.-W.; Yang, S.-C.; Liu, Y.-M.; Wu, M.-J. 192. An, P.; Yu, Z.; Lin, Q. Org. Lett. 2013, 15, 5496e5499. Tetrahedron 2009, 65, 8367e8372; (c) Katritzky, A. R.; Singh, S. K. J. Org. Chem. 193. Yu, Z.; Ho, L. Y.; Lin, Q. J. Am. Chem. Soc. 2011, 133,11912e11915. 2002, 67, 9077e9079. 194. Yu, Z.; Ohulchanskyy, T. Y.; An, P.; Prasad, P. N.; Lin, Q. J. Am. Chem. Soc. 2013, 153. Habib, P. M.; Raju, B. R.; Kavala, V.; Kuo, C.-W.; Yao, C.-F. Tetrahedron 2009, 65, 135, 16766e16769. 5799e5804. 195. Yu, Z.; Lin, Q. J. Am. Chem. Soc. 2014, 136,4153e4156. 154. (a) Katritzky, A. R.; Rachwal, S.; Rachwal, B. J. Chem. Soc., Perkin Trans. 1 1987, 196. Gann, A. W.; Amoroso, J. W.; Einck, V. J.; Rice, W. P.; Chambers, J. J.; Schnarr, N. 805e809; (b) Katritzky, A. R.; Kuzmierkiewicz, W. J. Chem. Soc., Perkin Trans. 1 A. Org. Lett. 2014, 16,2003e2005. 1987,819e823; (c) Katritzky, A. R.; Drewniak, M. J. Chem. Soc., Perkin Trans. 1 197. Soriano del Amo, D.; Wang, W.; Jiang, H.; Besanseney, C.; Yan, A. C.; Levy, M.; 1988, 2339e2344. Liu, Y.; Marlow, F.; Wu, P. J. Am. Chem. Soc. 2010, 132, 16893. 155. (a) Katritzky, A. R.; Lan, X.; Yang, J. Z.; Denisko, O. V. Chem. Rev. 1998, 98, 198. Besanceney, C.; Jiang, H.; Zheng, T.; Feng, L.; Soriano Del Amo, D.; Klivansky, L.; 409e548; (b) Katritzky, A. R. J. Heterocycl. Chem. 1999, 36, 1501e1522; (c) Liu, Y.; Marlow, F.; Wu, P. Angew. Chem., Int. Ed. 2011, 50, 8051. Katritzky, A. R.; Li, J.; Xie, L. Tetrahedron 1999, 55, 8263e8293; (d) Katritzky, A. 199. Wang, W.; Hong, S.; Tran, A.; Jiang, H.; Triano, R.; Liu, Y.; Chen, X.; Wu, P. Chem. R.; Denisko, O. V. Pure Appl. Chem. 2000, 72, 1597e1603; (e) Katritzky, A. R.; dAsian. J. 2011, 10, 2796e2802. Suzuki, K.; Wang, Z. Synlett 2005, 1656e1665; (f) Katritzky, A. R.; Manju, K.; 200. Jiang, H.; Zheng, T.; Lopez-Aguilar, A.; Feng, L.; Kopp, F.; Marlow, F. L.; Wu, P. Singh, S. K.; Meher, N. K. Tetrahedron 2005, 61, 2555e2581; (g) Katritzky, A. R.; Bioconjugate Chem. 2014, 25, 698e706. Rachwal, S. Chem. Rec. 2010, 110, 1564e1610. 156. (a) He, F.-Q.; Liu, X.-H.; Wang, B.-L.; Li, Z.-M. J. Chem. Res. 2006, 12, 809e812; (b) Caliendo, G.; Greco, G.; Grieco, P.; Novellino, E.; Perissutti, E.; Santagada, V.; Barbarulo, D.; Esposito, E.; Blasi, A. D. Eur. J. Med. Chem. 1996, 31, 207e213. M.S. Singh et al. / Tetrahedron 72 (2016) 5257e5283 5283

Biographical sketch

Maya Shankar Singh born in 1960 received his M.Sc. degree in Organic Chemistry from Banaras Hindu University, Varanasi, India in 1981, where he also earned his Ph.D. degree in 1986 working under the tutelage of Professor K.N. Mehrotra. After post- doctoral work, he joined Vikram University Ujjain in 1990 as Assistant Professor in Or- ganic Chemistry, and moved to Gorakhpur University as Associate Professor in 1998, Sushobhan Chowdhury was born in South 24 Parganas, West Bengal, India, in 1985. then to Banaras Hindu University in 2004, where he is currently Professor in Organic He received his B.Sc. degree from University of Calcutta in 2007 and moved to Banaras Chemistry since 2006. During his sabbatical, he visited Chemistry Department, Univer- Hindu University, Varanasi for post-graduate studies. There he obtained his M.Sc. de- sity of Arizona, Tucson, USA; Nagoya Institute of Technology, Nagoya, Japan; Loughbor- gree in 2010 and also completed Ph.D. under the supervision of Prof. Maya Shankar ough University, UK, University of Leicester, UK, and RWTH Aachen University, Aachen, Singh in 2014. His doctoral study was mainly themed on the development of synthetic Germany. His research interests are centered on synthetic Organic chemistry with spe- methods based on the dithioester chemistry. After completing his first postdoctoral re- cial emphasis in the development of novel building block precursors, new eco- search at UNIST, Ulsan, South Korea, currently he has started his second postdoctoral compatible synthetic methods, multicomponent domino reactions, and structural research at Ecole Polytechnique, France. studies. 19 students have completed their Ph.D. degrees under his supervision, which resulted the publication of 145 research articles and 6 reviews in journals of high sta- tus. Additionally, Prof. Singh has also authored three textbooks in organic chemistry published from Pearson-Education and Wiley-VCH, Weinheim, Germany. He has been elected Fellow of the Indian Academy of Sciences, India in 2013.

Suvajit Koley was born in Hooghly, West Bengal, India, in 1989. He graduated in 2009 from University of Calcutta, India. After obtaining his M.Sc. degree in chemistry in 2011 from the Banaras Hindu University, Varanasi, he joined the research group of Professor Maya Shankar Singh in the same department in October 2011 and is working on the topic construction of heterocycles and related systems utilizing dithioester and acetals for his Ph.D. degree.