Coupling, Cadiot-Chodkiewicz

Propiolaldehyde diethyl acetal has found numerous synthetic applications in the literature which may be briefly summarized. The compound has been utilized in the synthesis of unsaturated and polyunsaturated acetals and aldehydes by alkylation of metal-lated derivatives, " by Cadiot-Chodkiewicz coupling with halo acetylenes, " and by reaction with organocuprates. Syntheses of heterocyclic compounds including pyrazoles, isoxazoles, triazoles, and pyrimidines have employed this three-carbon building block. Propiolaldehyde diethyl acetal has also been put to use in the synthesis of such natural products as polyacetylenes " and steroids. ... 

The oxidative coupling, however, normally provides better results, as was demonstrated by the reasonably efficient cyclization of 179 to the homoconjugated 16-membered macrocycle 180 (14% yield) with alternating ethyne and butadiyne units (Scheme 34) the alternative Cadiot-Chodkiewicz coupling of the bisterminal diyne 38 and the dibromotriyne 177 gave only a 2.6% yield of 180 [4]. 

The dimerization of terminal alkynes, known as the Glaser coupling, the Eglinton coupling, and the Cadiot-Chodkiewicz coupling, is one... 

Later, Jones et al. applied this Cadiot-Chodkiewicz coupling reaction to the synthesis of triynoic acid, a fungal polyacetylene (Eq. 4.21).41... 

The monomer used in our studies was synthesized by Cadiot-Chodkiewicz Coupling (14) of 1-iodooctadecyne and 10-Undecynoic acid. 10 Undecynoic acid was used as received from Farchan Labs... 

Aryl-acetylene synthesis, Cf. Cadiot-Chodkiewicz coupling and Sonogashira coupling. The Castro-Stephens coupling uses stoichiometric copper, whereas the Sonogashira variant uses catalytic palladium and copper. 

An alternative mechanism similar to that of the Cadiot-Chodkiewicz coupling ... 

Z,Z-C2H5SCH=CHCH=CHCaC-r-Bu (undistilled) is obtained from Z-C2HjS--CH CHC=CCsC-t-Bu by a similar procedure (1 h reflux). The starting compound is prepared by Cadiot-Chodkiewicz coupling of Z-CjHjSCf CHGsCH with BiO C-t-Bu... 

A coupling procedure particularly suited to the synthesis of unsymmetrical diacetylenes involves the reaction of a terminal acetylene with a 1-bromo-acetylene in the presence of a catalyst consisting of a solution of copper(i) chloride in a primary amine to which small quantities of hydroxylamine hydrochloride is added (the Cadiot-Chodkiewicz coupling). 

Gung and Dickson reported the synthesis of this molecule [54] using a three-component Cadiot-Chodkiewicz coupling reaction [55] as the pivotal step (Scheme 12.17). In this three-component reaction, diyne 112 was utilized as a bidirectional synthon and was coupled successively with bromo alkynes 111 and 113 under... 

Sometimes the triethylsilyl grouping is more suitable for poly-acetylene synthesis because of its greater stability, namely in the Cadiot-Chodkiewicz coupling reaction44 of a halogenoacetylene with unprotected l-phenyl-buta-l,3-diyne (39)... 

A valuable alternative is the Cadiot-Chodkiewicz Coupling which allows the preparation of asymmetric bisacetylenes. 

Whereas Glaser-type oxidative coupling opens efficient synthetic pathways toward symmetrical diynes, its performance in heterocoupling is poor. The latter may be accomplished by Cadiot-Chodkiewicz coupling of terminal alkynes with 1-haloalkynes (usually 1-bromoalkynes). The reaction is conducted in the presence of an amine and catalytic amounts of a copper(I) salt. Because, in contrast with the Glaser-type reactions described above, it follows a nonoxidative reaction mechanism, oxygen is not necessary - but needs often not to be excluded (Scheme 4) [9]. 

Scheme 9. Side-reaction observed in Cadiot-Chodkiewicz couplings (X= I, Br) [11 a].

General procedure for Cadiot-Chodkiewicz Couplings CH3OH, H, CuCl... 

Fig. 16.9. Uncatalyzed, i.e. "true" Cadiot-Chodkiewicz coupling. The catalyzed variant is presented in Figure 16.33.

Fig. 16.33. Pd(0)-catalyzed alkynylation of a copper acetylide with a silylated ethynyl iodide in a two-step synthesis of a monosilylated 1,3-butadiyne. If the same copper acetylide is alkynylated with higher alkynyl iodides and subsequently heated with potassium carbonate in toluene, monoalkylated 1,3-butadiynes result - The Pd-free alkynylation of a copper acetylide ("Cadiot-Chodkiewicz coupling") is shown in Figure 16.9.

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