Cycloisomerization/Diels-Alder cycloaddition

In 2005, Yamamoto et al. reported the synthesis of polycyclic pyrrole-2-carboxylates 76 via a CuBr -catalyzed three-component coupling of A-benzylallylamine, ethyl gly-oxalate, and terminal alkynes, and subsequent ttansforma-tion of the glycine-tethered 1,6-enynes 75 thus obtained through a cycloisomerization/Diels-Alder cycloaddition/ dehydrogenation sequence under iridium-catalyzed conditions (Scheme 3.43) [108]. 

SCHEME 343 Synthesis of polycyclic pyrrole-2-carboxylates via CuAAC/cycloisomerization/Diels-Alder cycloaddition/dehydrogena-tion sequence. 

SCHEME 4.5 Scope of the cycloisomerization/Diels-Alder cycloaddition/allylboration multicomponent process. 

Carboni and coworkers developed the appUcation of a one-pot palladium-catalyzed cycloisomerization reaction between enynes 6/Diels-Alder cycloaddition/allylboration sequence to efficiently generate tricyclic structures 7 with complete control of the four new stereogenic centers formed in this process (Scheme 4.5) [6]. 

Silver salts or reagents have received much attention in preparative organic chemistry because they are useful catalysts for various transformations involving C-G and C-heteroatom bond formation.309 Especially, the silver(i)/ BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthalene) system is a very effective catalyst for a variety of enantio-selective reactions, including aldol, nitroso aldol, allylation, Mannich, and ene reactions. Moreover, silver salts are known to efficiently catalyze cycloisomerization and cycloaddition reactions of various unsaturated substrates. Recently, new directions in silver catalysis were opened by the development of unique silver complexes that catalyze aza-Diels-Alder reactions, as well as carbene insertions into C-H bonds. 

As 1,/2-alkenes, 1,6-derivatives are used very frequently leading to five-membered heterocycles, while the use of 1,7-derivatives, which produce six-mem-bered heterocycles, is very rare. The reactions of 1,6-dienes, -enynes, and -diynes are classified into three groups (a) cycloisomerization, (b) tandem addition— cyclization, and (c) cycloaddition, such as the Pau-son—Khand reaction, cyclotrimerization, and the Diels—Alder reaction (Scheme 15).97 In these reactions five-membered heterocycles are constructed upon the carbon—carbon bond-forming processes. 

Recently, Hoye and coworkers [257, 258] reported a new fluorenone synthesis by a novel hexadehydro-Diels-Alder (HDA) reaction (Scheme 6.109). In the HDA reaction, a 1,3-diyne 418 is engaged in a [4+2] cycloisomerization with a diynophile to produce the highly reactive benzyne intermediate 419. When trapping reagents are absent, the generated benzyne 419 undergoes a cycloaddition reaction with benzene as the solvent to form adduct 420. 

Cycloaddition reaction of two molecules of alkyne and alkene is a direct route for the synthesis of substituted cyclohexadiene derivatives, which are important components of the Diels-Alder reaction. Therefore, the reaction cycloisomerization of enediyne azamacrocycles represents a pathway to the synthesis of highly functionalized tetra-condensed cyclo-hexadienes in a single step. The synthetic variety of such reactions is... 

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