Sonogashira reaction tandem

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]. 

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. 

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... 

To investigate the mechanism when a blank experiment was performed for the tandem C-N/Sonogashira reaction in the absence of Pd/C under the optimized conditions the formation of a significant amount of 2-bromoindole,... 

Kaspar and Ackermann also reported that the process could be performed as a three-component system, featuring in situ generation of the key o-alkynylhaloarenes via the incorporation of a tandem Sonogashira reaction [35]. Related chemistries have been reported for the synthesis of 2-aminoindoles from ynamide-based substrates [36], A-aminoindoles from hydrazine-based nucleophiles [37], and N-unsubstituted indoles via the use of ammonia as the coupling partner [38,39],... 

Also exploiting an intramolecular C—S bond formation, Bryan et al. extended their investigation of gem-dihalovinylarene substrates in the synthesis of heterocycles to encompass a thiol analogue (Scheme 34.38, disconnection D-2). The combination of an unusual palladium-catalyzed S-alkenylation with a second cross-coupling process, such as a Suzuki, Heck, or Sonogashira reaction led to diversely functionalized benzothiophenes such as 67, produced in excellent yield (Scheme 24.40) [132], Routes incorporating a tandem carbonylation step [133] and a direct arylation [117] process have subsequently been reported. 

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...

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. 

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... 

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. ... 

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. 

BuendiaJ, Darses B, Dauban P. Tandem catalytic C(sp )-H amination/sila-Sonogashira-Hagihara coupling reactions with iodine reagents. Angew Chem Int Ed. 2015 54 5697-5701. 

In 2012, Teiber and Muller reported an efficient one-pot, three-component, consecutive Sonogashira-Fiesselmann cyclocondensation tandem reaction of alkyne, benzoyl chloride, and ethyl 2-mercaptoacetate to afford 2,4-disubstituted thiophenes [50]. We then developed this promising tandem reaction into the first... 

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