Alkynes Sonogashira cross coupling

Type of reaction C-C bond formatitMi Reaction conditions Dioxane, room temperature Synthetic strategy Aiyl bromide - alkyne Sonogashira cross-coupling Catalyst Pd(PhCN)2Cl2 / P(t-Bu>3... 

A palladium catalyst with a less electron-rich ligand, 2,2-dipyridyl-methylamine-based palladium complexes (4.2), is effective for coupling of aryl iodides or bromides with terminal alkynes in the presence of pyrrolidine and tetrabutylammonium acetate (TBAB) at 100°C in water.37 However, the reactions were shown to be faster in NMP solvent than in water under the reaction conditions. Palladium-phosphinous acid (POPd) was also reported as an effective catalyst for the Sonogashira cross-coupling reaction of aryl alkynes with aryl iodides, bromides, or chlorides in water (Eq. 4.18).38... 

Scheme 10.2 shows a protocol for synthesizing 1 and its further transformation into 4 [13a,d], Monolithiation of the diiodide 9 followed by treatment with S8 and AcCI generated 1. Next, a Sonogashira cross-coupling reaction with trimethylsilyl-acetylene afforded 10 in high yield. Desilylation was obtained upon treatment with n-Bu4NF, which provided the terminal alkyne 4. 

Scheme 10.7 depicts the synthesis of an OPE3 one-terminal wire compound by repeated Sonogashira cross-couplings [13c]. The synthesis takes advantage of the more reactive iodide as compared with the bromide, which allows for stepwise scaffolding. Thus, two concomitant Pd-catalyzed cross-couplings of 23 produced 24. The terminal alkyne obtained after desilylation was subsequently cross-coupled with 1 to afford 25. 

Scheme 5 Alkynones 8 by modified Sonogashira cross coupling of acid chlorides 7 and alkynes 4...

The mechanism of the Sonogashira cross-coupling follows the expected oxidative addition-reductive elimination pathway. However, the structure of the catalytically active species and the precise role of the Cul catalyst is unknown. The reaction commences with the generation of a coordinatively unsaturated Pd species from a Pd " complex by reduction with the alkyne substrate or with an added phosphine ligand. The Pd " then undergoes oxidative addition with the aryl or vinyl halide followed by transmetallation by the copper(l)-acetylide. Reductive elimination affords the coupled product and the regeneration of the catalyst completes the catalytic cycle. 

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. 

Pd and Cu-catalyzed Sonogashira cross-coupling Cu-Pd-catalyzed coupling of terminal alkynes with aryl and vinyl halides to give envnes. 424... 

Cu-catalyzed alkynation of L Pd and cross-coupling with R -X, has developed into a widely used method for forming new C-C bonds between alkynyl and aryl or vinyl groups. This transformation is now called Sonogashira cross-coupling. Equation 12.72 shows a typical example of the Sonogashira reaction.146... 

Type of reaction C-C bond formation Reaction condition solvent-free Keywords Sonogashira cross-coupling, alkyne... 

Recently, Fu has developed a catalyst for Sonogashira cross-couplings of unactivated primary alkyl bromides and iodides with an array of alkynes (Eq. 14)... 

Table 9 Sonogashira cross-couplings of primary alkyl bromides and iodides with alkynes...

Camptothecin (127) is an alkaloid with potent anti-tumor activities. SAR studies showed that substitution at the 7-position of 127 led to compounds, such as SN-38 (128) and BNP-1350 (129), with improved biological activity. The Sonogashira cross-coupling of the advanced intermediate 130 with alkyne 131 afforded the common intermediate 132 for the assembly of both 128 and 129. ... 

TABLE 5. Alkyne Synthesis Via Sonogashira Cross-Coupling (cf. Sect. III.2.8.1)... 

The alkynyl functionality of alkynones 1 is perfectly suited for subsequent copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in the sense of an MCR (2015ASC(357)617). A microwave-assisted three-component reaction of aroyl chlorides 4, TMS-substituted acetylene (5a), and benzyl azide (10a) consisting of modified Sonogashira cross-coupling I, desilylation, and CuAAC furnishes 4-disubstituted 1,2,3-triazoles 11 in moderate to excellent yields (Scheme 5) (201 OOL(12)4936). 

The terminal alkyne can also be generated in situ via copper-free Sonogashira cross-coupling of trimethylsilyl acetylene (5a) and aryl halides 6 and subsequent cleavage with TBAF, caibonylation, and cyclization (Scheme 26) (20090L(11)3210). This microwave-assisted sequence allows the rapid synthesis of the title compounds in moderate to good yields. Each compound can be easily varied with exception to trimethylsilyl acetylene. The application of electron-rich aryl bromides and iodides expectedly decreases the yields. 

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