Sonogashira tandem

Sonogashira/nucleophilic addition (Scheme 7.34) [70], The reaction started by the Ugi-4CR, giving the intermediate 82, which was transformed into the enyne 83 by a Heck-Sonogashira tandem reaction. Finally, the activated enyne evolved an aza-Michael-type addition to give the final six-component product 84. 

Scheme 22. Schreiber s approach to dynemicin A system 86 by a tandem Sonogashira coupling/Diels-Alder reaction.

NHC-Pd(ll) complexes have also been used in tandem reactions involving a Sonogashira couphng and hydroalkoxylation of the resulting alkyne for the synthesis of benzofurans [131] as well as sequential Heck-Sonogashira couphngs [132] (Scheme 6.44). 

Scheme 6.44 Tandem Sonogashira-hydroaUcoxylation and Sonogashira-Heck reactions...

Tandem Sonogashira reactions starting with iodopyrrole 122 have furnished the dipyrrolylacetylene 124, and dimerization of 123 gives 125 [86], The Sonogashira coupling has also been reported for enol triflate 55 reacting with an /V-protected propargyl amine [81]. 

A methodology for the synthesis of substituted thiazolo[3,2-rz]benzimidazoles 250 from 2-propargylmercapto benzimidazole 249 was developed based on a tandem Sonogashira cross-coupling with iodoaryls and a subsequent exocyclic heterocyclization (Equation 109) <2004TL5747>. 

Harmata et al. have developed a tandem Sonogashira/nitrogen-addition reaction of acetylenes 261 to sulfonamide 262 to prepare S(vi)-oxidized compounds 263 and 264 (Scheme 36) <20050L143>. When R = alkyl (e.g., Pr"), the 1,2-thiazine 263 is the major product (70%) formed via a endocyclization process, along with a minor amount (20%) of exocyclized product 264, while the five-membered ring product 264 (81%) is preferred when R= Ph. 

With respect to this, Ellman and coworkers [16], Zhu and coworkers [17], Amusch and Pieters [18], and Liskamp and coworkers [19] have prepared (monocyclic) mimics of the D-E part of the cavity of these antibiotics via an intramolecular nucleophilic aromatic substitution [16-18] or a Sonogashira-based macrocyclization [19] (Figure 1.4). Recently, a bicydic mimic of the C-D-E cavity, which was prepared by a Stille reaction followed by tandem ring-dosing metathesis (9, Figure 1.4), was described by liskamp and coworkers [20]. Considerable challenges lie ahead for the synthetic chemist in order to develop practical syntheses of mimics of vancomydn capable of binding not only D-Ala-D-Ala, but also cell wall parts of resistant bacteria, i.e. D-Ala-D-lactate. 

Fig. 44 Tandem carbonylation/Sonogashira coupling sequences of alkyl halides...

A variety of structurally diverse 2-alkynyl benzo[Z>]furans were synthesized by a tandem Pd/C- and Cul-catalyzed tandem Ullmann/Sonogashira coupling reaction from gem-dibromovinyl substrates and terminal alkynes <07OL2955>. 

Pettier LR, Peyrat JF, Alami M, Brion JD (2004) Unexpected tandem sonogashira-carbo-palladation-sonogashira coupling reaction of benzyl halides with terminal alkynes a novel four-component domino sequence to highly substituted enynes. Synlett 1503-1508... 

Okamoto et al. [19] described the direct synthesis of the benzimidazo [2,1-a] isoquinoline (x) ring system by a microwave-accelerated tandem process in which a sonogashira coupling, 5-endocyclization, oxidative aromatization and 6-endo cyclization can be performed in a single synthetic operation. 

Tandem Sonogashira reactions beginning with 40 readily assembled 358. This com-... 

Schreiber s early efforts in this area were focused on libraries of compounds having structural features reminiscent of rigid, complex, stereochemically rich natural products. In a key early example, solid-phase split-pool synthesis was used to generate a combinatorial library of over two million complex, polycyclic compounds derived from shikimic acid [17]. A stereoselective tandem acylation-nitrone cycloaddition was used to generate 18 tetracyclic scaffolds, to which 30 alkynes were coupled using a Sonogashira reaction, 62 amines were coupled via y -lactone aminolysis, and 62 carboxylic acids were coupled by alcohol esterification (Fig. 9.1-3(c)). In addition, a portion of the solid supports were left unreacted at each of the last three steps to generate a skip codon that further increased the diversity of the library. 

Aryl and alkyl-substituted diynes and tetraynes have been synthesized in good yields (82-99%) by TBAF-promoted desily-lation and Cu-catalyzed oxidative dimerization of triisopropylsi-lyl (TlPS)-protected acetylenes (eq 38). Copper acetate was used as oxidant in this reaction. Aryl- and alkenyl alkynes were made under similar conditions (eq 39). Pd/C with TBAF was used in ligand- and copper-free, one-pot, domino Halex-Sono-gashira reactions. Similarly, TBAF promoted the synthesis of 2-substituted indoles by a tandem Sonogashira/cyclization reaction of 2-iodoanilines and terminal alkynes. ... 

The Sonogashira coupling was applied to the synthesis of an indole-containing KDR kinase inhibitor by tandem Sonogashira coupling/5-ew[Pg.99]

Since aikenes and aikynes can be prepared via Heck and Sonogashira reactions, respectively, tandem processes are also possible for lactone synthesis [71-77]. Appropriately, o-iodobenzoic acids can generate both phthalide and isocoumarin derivatives under Pd catalysis, with a Cul co-catalyst favoring the former and... 

Scheme 2.28 Regioselective tandem Sonogashira/hydrocarboxylation of alkynes [71, 72],...

Rapid method to prepare 3,4-disubstituted 2-trifluoromethylqumolines 94 by a palladium catalyzed tandem Sonogashira-alkyne carbocyclization of p-trifluoro-methyl p-enaminoketones 93 with arynes has been suggested (Scheme 38) [59]. 

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