Coupling of acid chlorides with terminal

An alternative approach to multicomponent heterocycle synthesis involves the use of palladium catalysis to construct keto-alkynes for cycloaddition reactions. Muller has demonstrated the power of this approach in the construction of a range of aromatic heterocycles. For example, the palladium-catalyzed coupling of acid chlorides with terminal alkynes provides a method to assemble 36. The trapping of this substrate can provide routes to aromatic heterocycles. As an example, the addition of amidines provides a multicomponent synthesis of pyrimidines (Scheme 6.69) [97]. This same substrate 36 is available via the carhonylative coupling of aryl halides with terminal alkynes, providing a four-component synthesis of pyrimidines (98j. 36 can also be employed in 1,3-dipolar cydoaddition reactions. For example, cydoaddition... 

A carbonyl group in conjugation with the triple bond exerts a strong polarization of the alkyne. Thus, Sonogashira coupling of acid chlorides 7 and terminal alkynes... 

A seemingly simple method for the coupling of acid chlorides to acetylenes which avoids the use of copper acetylides employs mixtures of copper(i) iodide, tri-phenylphosphine, and palladium(ll) chloride as catalysts. By treating terminal acetylenes with dimethylcarbamoyl chloride under these conditions, high yields of 2-alkynamides (159) may be obtained. ... 

Trisubstituted isoxazoles 14 with ferrocenyl groups in 4- and 5-position can be synthesized utilizing acid chlorides 4, terminal alkynes 5, and hydroximinoyl chlorides 13 in a sequence consisting of modified Sonoga-shira cross-coupling I and cyclocondensation. Hydroximinoyl chlorides 13 are employed as synthetic equivalents of the corresponding aromatic nitrile... 

Zanina et al. have reported a method for the synthesis of a, acetylenic ketones from terminal alkynes and acid chlorides using cuprous iodide as a catalyst. The use of high temperature and toluene as the solvent in this protocol prompted Kundu and co-workers to develop a new procedure with triethylamine as the solvent and the base, which obviated many of the difficulties and enabled the reactions to be carried out at room temperature (eq 30). Zhang and co-workers have modified the conditions in order to couple monooxalyl chloride with terminal alkynes THE was used as the solvent with 2 equiv of triethylamine and 5 mol % of Cul. It is noteworthy that CuCl, CuBr, and Cul showed similar reactivity, while CuOTf was totally inert. 

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... 

PLLA-fr-PCL) multiblock copolymers were prepared from the coupling reaction between the bischloroformates of carboxylated PLLA with diol-terminated PCL in the presence of pyridine [140]. LLA was polymerized with SnOCt2 and 1,6-hexanediol followed by the reaction with succinic anhydride to provide the dicarboxylated PLLA. The carboxyl end groups were subsequently transformed to acid chloride groups by the reaction with thionyl chloride (Scheme 65). As expected, the molecular weight distributions were broad for all samples (1.84 < Mw/Mn < 3.17). 

A similarly high performance has been reported for oxime-derived (125) and benzylsulfide-derived (126) palladacycles.438 These precatalysts are effective in the cross-coupling of arylboronic acids,438,439 organotin compounds,440 and terminal acetylenes441 with aryl iodides and bromides, and of activated aryl chlorides. SC-palladacycles can effect the Suzuki-Miyaura reaction even at room temperature. 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

---