Sonogashira synthesis

A more recent example sees the conversion of an aryl ether (9) to an Af-aryl-2-hydroxypropion-amide (10) in high overall yields from the starting materials, ultimately leading to a two-step Smiles-Sonogashira synthesis of indoles from 2,3-dihalophenols [5]. 

Review, K. Sonogashira, Comprehen.tivc Organic Synthesis, Vol. 3. p. 521. Pcrgamon Press, 1990. 

The original Sonogashira reaction uses copper(l) iodide as a co-catalyst, which converts the alkyne in situ into a copper acetylide. In a subsequent transmeta-lation reaction, the copper is replaced by the palladium complex. The reaction mechanism, with respect to the catalytic cycle, largely corresponds to the Heck reaction.Besides the usual aryl and vinyl halides, i.e. bromides and iodides, trifluoromethanesulfonates (triflates) may be employed. The Sonogashira reaction is well-suited for the synthesis of unsymmetrical bis-2xy ethynes, e.g. 23, which can be prepared as outlined in the following scheme, in a one-pot reaction by applying the so-called sila-Sonogashira reaction ... 

Scheme 19. The Sonogashira coupling in Nicolaou s synthesis of (12S)-HETE (78).

In 1980 Sonogashira reported a convenient synthesis of ethynylarenes - the Pd-catalyzed cross-coupfing of bromo- or iodoarenes with trimethylsilylacetylene followed by protiodesilylation in basic solution [15]. Prior to this discovery, formation of terminal acetylenes required manipulation of a preformed, two-carbon side chain via methods that include halogenation/dehydrohalogenation of vinyl- and acetylarenes, dehalogenation of /1,/1-dihaloalkenes, and the Vils-meier procedure [ 14]. With the ready availability of trialkylsilylacetylenes, the two-step Sonogashira sequence has become the cornerstone reaction for the construction of virtually all ethynylated arenes used in PAM and PDM synthesis (vide infra). 

Vollhardt et al. recently reported the synthesis of hexaethynylated PAM 11 using a combined Sonogashira/Stephens-Castro approach [20]. The requisite compound for cyclization, molecule 12, was prepared in stepwise fashion from 1,2,3,4-tetrabromobenzene. Regioselective alkynylation at positions 1 and 4 afforded dibromophenyldiacetylene (13), which was then monoalkynylated at... 

Synthesis of Ni/Pd bimetallic core/shell nanoparticles and their applications to Sonogashira coupling reactions... 

Sonogashira Couplings Investigated in Micro Reactors Organic synthesis 46 [OS 46) Copper-free Son<%ashira 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... 

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). 

The coupling of terminal alkynes with organic halides, known as the Castro-Stephens-Sonogashira reaction, has wide applications in synthesis. The most widely used method is the Sonogashira coupling, using a combination of palladium and copper as the catalyst.13 Recently,... 

Sonogashira, K., in Handbook of Organopalladium Chemistry for Organic Synthesis, Negishi, E., ed. Wiley, Hoboken, 2002, p. 493. 

Fiandanese and coworkers [103] described a new approach for the synthesis of the butenolides xerulin (6/1-207) and dihydroxerulin (6/1-208), which are of interest as potent noncytotoxic inhibitors of the biosynthesis of cholesterol (Scheme 6/1.53). The key transformation is a Pd°-catalyzed Sonogashira/addition process of 6/1-204 or 6/1-206 with (Z)-3-iodo-2-propenoic acid 6/1-205, which is followed by the formation of a lactone to give 6/1-207 and 6/1-208, 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... 

Scheme 14 illustrates Linstrumelle s synthesis of (9Z,11 )-9,11,13-tetradeca-trienyl acetate (8), the pheromone of the pyralid moth, Stenoma cecropia [25]. The key steps were palladium and copper-catalyzed Sonogashira couplings (A+B and C+D). Another noteworthy feature in this synthesis was the use of activated zinc dust in aqueous methanol for the reduction of the triple bonds of E to give two double bonds of 8. 

Cross-coupling of terminal acetylenes used as nucleophiles with aryl or alkenyl halides (referred to as the Sonogashira-Hagihara, or SH, reaction) is a versatile method of synthesis for acetylenic compounds, which are rapidly gaining importance as advanced new materials and building blocks for implementing unusual molecular architectures. 

R. Dominique, B. Liu, S. K. Das, and R. Roy, Synthesis of molecular asterisks via sequential cross-metathesis Sonogashira and cyclotrimerization... 

---