Natural products Sonogashira reaction

The Sonogashira reaction is a transition metal-catalyzed coupling reaction which is widely used for the preparation of alkyl-, aryl- and diaryl-substituted acetylenes (Table 4.7) [120]. This reaction is a key step in natural product synthesis and is also applied in optical and electronic applications. Sonogashira reactions involve the use of an organic solvent with a stoichiometric portion of a base for capturing the... 

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... 

Advantage has been taken of the aforementioned observations in the synthesis of a terthiophene natural product, arctic acid (147) [123]. Pd-catalyzed carbonylation of bromobisthiophene 25, obtained from the Kumada coupling of 2-thienylmagnesium bromide and 2,5-dibromothiophene, gave bithiophene ester 144, which was converted to iodide 145 by reaction with iodine and yellow mercuric oxide. Subsequent propynylation of 145 was then realized using the Sonogashira reaction with prop-l-yne to give bisthienyl alkyne 146, which was subsequently hydrolyzed to 5 -(l-propynyl)-2,2 -bithienyl-5-carboxylic acid (147), a natural product isolated from the root of Arctium lappa. 

Akita and Ohta disclosed one of the earliest Sonogashira reactions of chloropyrazines and their A-oxides [24, 25]. The union of 2-chloro-3,6-dimethylpyrazine (23) and phenylacetylene led to 2,5-dimethyl-3-phenylethynylpyrazine (29). Subsequent Lindlar reduction of adduct 29 then delivered (Z)-2,5-dimethyl-3-styrylpyrazine (30), a natural product isolated from mandibular gland secretion of the Argentine ants, Iridomyrmex humilis. 

Like halopyridines, diazines participate in Sonogashira coupling too. 3,6-dimethyl-2-chloropyrazin, for example on coupling with phenylacetylene under standard conditions, gave the desired compound in good yield, which was further reduced to give a natural product (7.36.)51 (NB. the Heck reaction, which could be considered as an alternate approach would be expected to furnish predominantly the c/.v-olcfin as product). 

Removal of the tri-wo-propylsilyl (TIPS) and tm-butyldimethylsilyl (TBS) protecting groups could be accomplished concomitantly with TBAF in tetrahydrofuran at 0 °C, but here competing elimination of the secondary bromide was observed. Better overall yields and cleaner conversion was observed when TBS ether was cleaved with 5 % aqueous HF in acetonitrile at 0 °C followed by removal of the acetylenic TIPS with TBAF under milder conditions of -78 °C.10 The diastereomers are not separated before the desilylation process therefore even a 3 1 mixture of E- and Z-enyne is obtained. Prelaureatin 4 and its F-isomer 17 are likewise goals in natural product synthesis. Crimmins and co-workers developed an own synthetic route to 4. The reaction sequence is similar up to aldehyde 55. Afterwards a Z-vinyl-iodide is selectively formed and the alkyne is introduced via a Sonogashira reaction. 

Prclaureatin 4 and its E-isomcr 17 are likewise goals in natural product synthesis. Crimmins and co-workers developed an own synthetic route to 4. The reaction sequence is similar up to aldehyde 55. Afterwards a Z-vinyl-iodide is selectively formed and the allcyiie is introduced via a Sonogashira rcaction. 

The novel heliannane-type sesquiterpenoid (-)-heliannuol E was synthesized in the laboratory of K. Shishido. Interest in the total synthesis of this natural product was not only spurred by its irregular terpenoid structure and significant biological activity but the need to establish the absolute stereochemistry at the C2 and C4 stereocenters. The Sonogashira reaction was utilized to prepare the 3-arylpropargyl alcohol by coupling of a heavily substituted aryl iodide with an unprotected propargyl alcohol in quantitative yield. 

In recent years, several natural products containing 2,4-disubstituted oxazoles have been isolated and their synthetic routes were investigated. Several key intermediates required for the synthesis of target compounds were achieved via the Stille, Suzuki, Heck, and Sonogashira reactions. In addition, several 2,5-diaryloxzoles were prepared from 2-halo-... 

The Sonogashira coupling reaction of terminal alkynes with aryl or vinyl halides is a useful tool for carbon—carbon bond formation, and has found wide employment in areas such as natural product synthesis, the pharmaceutical industry, and material sciences. Novel recyclable Pd catalysts with fluorous ponytails in the ligand 2,2 -bipyridine were reported in a copper-free Pd-catalyzed Sonogashira reaction in a fluorous biphasic system (FBS) (Equation 4.19). The catalysts are only soluble in perfluorinated solvents at room temperature [41],... 

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. 

Examples of name reactions may be found by first considering the nature of the starting material and product. The Wittig reaction, for instance, is given in Section 199 (Alkenes from Aldehydes) and in Section 207 (Alkenes from Ketones). The aldol condensation may be found in the chapters on difunctional compounds in Section 324 (Alcohol, Thiol-Aldehyde) and in Section 330 (Alcohol, Thiol-Ketone). Examples of the synthetically important alkene metathesis reaction are provided primarily in Section 209 (Alkenes from Alkenes). Examples of the Heck reaction are presented in Section 74C, those for the Suzuki reaction in Section 70, and examples of the Sonogashira reaction are presented in Section 300. 

The best results for this procedure are obtained with bromoaUcynes, whereas iodoalkynes suffer from their more strongly oxidizing nature toward the Cu(I) ion, which leads to an increased formation of the by-product 72, and chloroalkynes generally show a lower reactivity. The reactivity of the terminal alkyne is similar to that described for the Sonogashira reaction. In general, arylacetylenes provide better results than alkylacetylenes. Less acidic alkynes have also been shown to produce larger quantities of the undesired 72 [182]. 

A singular feature of the Sonogashira reaction is the wide range of solvents that have been used, from benzene and toluene, to DMF and water. Even vodka has been used. The mild nature of the Sonogashira reaction makes it a singularly useful carbon-carbon bond-formation reaction. The enyne natural product. 

The challenge of the synthesis of the ene-diyene natural products was one of the factors that brought the Sonogashira reaction to prominence. Three Sonogashira reactions were used in a synthesis of the core of the esperamycin/calichemicin anti-tumour agents (Scheme 2.117). Two were employed in sequence to add two alkynes onto cw-l,2-dichloroethylene 2375 to form the ene-diyne 2376. Due to the sensitivity of propiolaldehyde, its diethyl acetal was employed. After hydrolysis of the acetal, a diene unit was installed. 

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