Alkyne derivatives Sonogashira synthesis

The alkyne derivatives were used for the synthesis of boron-containing nucleosides [56] and porphyrins [60] using click reaction and Sonogashira reaction, respectively. 

Snieckus and his group members [104] used the known domino Sonogashira/ Castro-Stephens reaction [105, 106] for the synthesis of the natural product pli-cadin (6/1-209), this having been isolated from Psorelia plicata in 1991 [107]. In this synthesis, Pd°-catalyzed reaction of the alkyne 6/1-210 and the iodobenzene derivative 6/1-211 in the presence of Cul led to the furan 6/1-212, which was transformed into 6/1-209 via 6/1-213 (Scheme 6/1.54). There are some discrepancies of the physical data of the natural and the synthetic product thus, it might be possible that the natural product has a different structure. It should also be mentioned that the... 

Wang s approach for the synthesis of enyne-allenes focused on ene-allenyl iodide 45 (Scheme 14.12) [24]. Palladium-catalyzed Sonogashira reaction of 45 with terminal alkynes 46 (R= Ph or CH2OH) proceeded smoothly under mild reaction conditions in the presence of the cocatalyst cuprous iodide and n-butylamine. The initially formed enyne-allene 47b with substituent R= CH2OH cyclized spontaneously to the corresponding a-methylstyrene derivative 48. 

The concise formal total synthesis of mappicine was accomplished using an intramolecular hetero Diels-Alder reaction as the key step by M. lhara and co-workers. Introduction of the necessary acetylenic moiety at the C2 position was achieved by the Sonogashira cross-coupling of a 2-chloroquinoline derivative with TMS-acetylene. Several substituents at the C3 position were investigated, and it was found that the unprotected hydroxymethyl substituent gave almost quantitative yield of the desired disubstituted alkyne product. 

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. 

One distinguishes palladium(0)- and palladium(ll)-catalysed reactions. The most common palladium(O) transformations are the Mizoroki-Heck and the cross-coupling transformations such as the Suzuki-Miyaura, the Stille and the Sonogashira reactions, which allow the arylation or alkenylation of C=C double bonds, boronic acid derivates, stan-nanes and alkynes respectively [2]. Another important palladium(O) transformation is the nucleophilic substitution of usually allylic acetates or carbonates known as the Tsuji-Trost reaction [3]. The most versatile palladium(ll)-catalysed transformation is the Wacker oxidation, which is industrially used for the synthesis of acetaldehyde from ethylene [4]. It should be noted that many of these palladium-catalysed transformations can also be performed in an enantioselective way [5]. 

The MgLa mixed oxide-supported Pd catalyst is air and moisture stable and highly efficient for the synthesis of benzofuran derivatives involving Sonogashira reachon between o-halo phenol and terminal alkynes. The reaction was performed in freshly distilled DMF and EtsN at 80°C for 24h to provide the product in more than 60% )deld (Scheme 47) [68]. Though the reactions witii o-iodo phenol provided moderate to high yields, in case of o-bromo and o-chloro phenol very low yields (less than 10%) were obtained. 

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