Heterocoupled diyne

During the biomimetic total synthesis of endiandric acids A-G by K.C. Nicolaou and co-workers, the key polyunsaturated precursor was assembled via the Giaser coupiing of two different terminal alkynes. " One of the alkynes was used in excess so the yield of the heterocoupled diyne could be maximized. In a solvent mixture of pyridine methanol (1 1), the two reactant alkynes were treated with Cu(OAc)2 at 25 °C to provide the desired diyne in 70% yield. 

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]. 

The preparation of enynes by the locoselective monohydroalumination of diynes can be exemplified by equation (69).In addition, a heterocoupling of adduct (58) with 1-halo-l-alkynes can produce conjugated enynes in high yield. 

The heterocoupling of a terminal alkyne with a 1-bromoalkyne in the presence of an aliphatic amine and a catalytic amount of a copper(I) salt affords unsymmetrically substituted diynes (2 equation 5). This useful reaction, discovered by Chodkiewicz and Cadiot, can be employed advantageously for the synthesis of several polyunsaturated systems. 

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