Three-component reactions alkyne termination

Gold has even shown its ability as a nucleophile activator in three-component reactions of terminal alkynes, aldehydes and amines [186]. In the case of chiral amines, excellent diastereoselectivities were obtained [187] (Scheme 8.29). ... 

Gold also catalyzed a three-component reaction comprising an ( )- or (Z)-2-(arylmethylene)cyclopropylcarbinol, a terminal alkyne and an alcohol to afford a tetrahydrofuran product <07OL4917>. 

This reaction type differs from die three-component reaction reported by Grigg et al. Thus, Grigg et al. [53] (Scheme 7) immobihzed 3-iodo-4-(N-acetyl-N-(2-methyl-2-propenyl)amino)benzoate (36) onto a sohd support. In the presence of suitable Pd salts, Pd substituted the iodide function of the aromatic. The proximal isopropyhdene group trapped the resulting metalated species in an intramolecular Heck reaction. The resulting alkyl palladium species (37) could then react with a suitable carbanion equivalent. The authors used vinylstaimanes or boronates for this purpose, which they obtained in situ from alkynes by hydroboration or hydro-starmylation. The latter procedure allowed them to attach the same vinylic species via its terminal carbon (boronate) (41) and its subterminal carbon (stannane) (39). 

Mishra and Ghosh (2011) found that Cu(l)-NaHS04 Si02 could be utilized as a novel and efQdent heterogeneous catalyst for the synthesis of imidazo[l,2-fl]pyri-dines using three-component reactions of 2-aminopyridines, aldehydes, and terminal alkynes in one pot (Scheme 4.56). Under this catalytic systan, diverse imidazo[l,2-fl]pyridine derivatives were generated in moderate to excellent yields. 

M. J. Campbell, F. D. Toste, Chem. Sci. 2011, 2, 1369-1378. Enantioselective synthesis of cyclic carbamimidates via a three-component reaction of imines, terminal alkynes, and p-toluenesulfonylisocyanate using a monophosphine gold(I) catalyst. 

Ranu et al. [45] introduced a completely different protocol where l,4-disubstituted-l,2,3-triazoles were synthesized by a simple one-pot three-component reaction of alkyl halide/aryl boronic acid, sodium azide, and terminal alkynes... 

M. Jeganmohan, S. Bhuvaneswari, C.-H. Cheng, Synthesis of N-arylated 1,2-dihydroheteroaromatics through the three-component reaction of arynes with N-heteroaromatics and terminal alkynes or ketones, Chem. Asian J. 5 (2010) 153-159. 

The efficient synthesis of aminoindolizines 53 was successfully achieved in PEG using copper(I) chloride catalyzed three-component reaction of pyridine- or quinolin-2-carboxaldehyde with terminal alkynes and secondary amines (Scheme 30) [54]. The reaction in conventional solvents gave lower yields of the product 53. The structure of the obtained aminoindolizines was confirmed by the X-ray crystallography data (53, R =4-MeC6H4, r2]sjr3=morpholino). 

S. Mishra, B. Naskar, R. Ghosh, GuGl catalyzed green and efficient one-pot synthesis of aminoindolizine frameworks via three-component reactions of aldehydes, secondary amines, and terminal alkynes in PEG, Tetrahedron Lett. 53 (2012) 5483-5487. 

Both copper- and silver-catalyzed three-component reactions between an aldehyde, terminal alkyne, and secondary amine have been used to generate propargylamines [17, 18] The copper-catalyzed hydroamination between hydroxylamine esters and unactivated aUcenes generates amines with the desired regiochemistry for a wide range of diverse substrates [20]... 

In a first study [137], the Cu-catalyzed three-component reaction between a terminal alkyne, a sulfonyl azide, and a secondary amine for double PPM purposes was established. Hence, alkyne-containing random copolymers based on polystyrene (PS) have been prepared and modified (Scheme 6). 

Scheme 6 Cu-catalyzed three-component reaction between a terminal alkyne, a sulfonyl azide, and a secondary amine for double PPM purposes...

A three-component reaction for the synthesis of functionalized benzimidazoles from terminal alkynes, o-aminoanilines, and / -tolylsulfonyl azide is developed by Wang and coworkers (Scheme 8.52). The C(sp)-H bond of alkyne was activated in this reaction via Cul-catalyzed azide-alkyne cycloaddtion (CuAAC) reaction which could lead to the formation of a ketenimine intermediate by the release of N2- The benzimidazoles could be obtained by intramolecular nucleophilic addition and subsequent elimination of amide intermediate with 2% H2SO4 under reflux conditions [91]. They also developed another protocol for the synthesis of substituted benzimidazole derivatives via a sequential three-component cascade reaction from sulfonyl azides, alkynes, and 2-bromoanilines using Cul as catalyst. Similarly, the C-H bond of alkyne was activated at the process of copper-catalyzed azide-alkyne cycloaddtion (CuAAC) reaction [92]. 

In addition to the heteroatom nucleophiles, carbon nuleophiles such as pyrroles were found by Cho and Chang [65] to be able to take part in the three-component reaction with sulfonyl azides and terminal alkynes to give the dual-functionalized pyrroles 98 (Scheme 5.63). The reaction depended on the presence of the N—H bond. When N-substituted pyrroles were used, reactions were sluggish and gave poor yields. Moreover, either indole or Af-methyl indole did not participate in the reaction. 

SCHEME 5.63 Cu(I)-catalyzed three-component reaction of sulfonyl azides, terminal alkynes, and pyrrole. 

The synthesis of p-hydroxy triazoles by the three-component reaction of a variety of epoxides, sodium azide, and diverse terminal alkyne reactions performed... 

Scheme 17 Iron-catalyzed three-component coupling reactions of aldehydes, terminal alkynes, and amines...

Recently, on the basis of the Markovnikov addition of water to alkynes, Trost et al. developed a three-component addition reaction of terminal alkynes, water, and methyl vinyl ketone, affording 1,5-diketones in DMF/water in the presence of ruthenium and indium catalysts (Eq. 4.38). 

A three-component coupling was used to prepare a series of 1,4-disubstituted-l,2,3-triazoles 129 from the corresponding acetylated Baylis-Hillman adducts 127, sodium azide and terminal alkynes 128 <06TL3059>. This same reaction was also carried out in either water or in... 

Multicomponent reaction systems are highly valued in solid-phase organic synthesis because several elements of diversity can be introduced in a single transformation.1 The Mannich reaction is a classic example of a three-component system in which an active hydrogen component, such as a terminal alkyne, undergoes condensation with the putative imine species formed from the condensation of an amine with an aldehyde.2 The resultant Mannich adducts contain at least three potential sites for diversification specifically, each individual component—the amine, aldehyde, and alkyne—can be varied in structure and thus provide an element of diversity. 

A novel gold catalyzed example of three-component addition was recently reported by Shi et al. (Equation 8.44) [106]. Terminal aryl alkynes, alcohols and 2-(arylmethy-lene) cyclopropylcarbinols provided an intermolecular tandem hydroalkoxylation/ Prins-type reaction to form 3-oxabicyclo[3.1.0]hexanes from simple materials and under mild conditions, catalyzed by the system AuClPPh3/AgOTf. The proposed mechanism for this reaction is shown in Scheme 8.19. 

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