Acetylene-zipper reaction

DMSO with Nal catalysis (Sonnet and Heath, 1980), by bromination of a terminal alkene followed by double elimination of HBr (Hoye el al., 1999), or by isomerization of an internal alkyne with the acetylene zipper reaction (Abrams, 1984). 

The acetylene zipper reaction is the shifting of a triple bond in any position of a straight chain internal alkyne to the terminus of the chain in the presence of a very strong base. This multipositional isomerization of the triple bond is especially interesting when applied to acetylenic alcohols as a route to long chain structures with chemically differentiated functionality. 

Scheme 9 outlines the synthesis of the (2S, 3R, 4R.5S, 14S)-isomer 57. Cleavage of 54 with the acetylide derived from 55 yielded 58, which was subjected to the acetylene-zipper reaction to give the (9R)-terminal acetylene... 

Negishi and Abramovitch have described an extremely elegant use of two generations of Brown chemistry in the four-step synthesis of the insect sex pheromone of the European grape vine moth Lobesia botrana, (7E,9Z)-dodeca-7,9-dien-l-yl acetate (101). The now familiar acetylene zipper reaction converts (102) into (103), the terminal acetylene (103) produced being then coupled via the borane (104) to give the ( )-dodec-7-en-9-yn-l-yl acetate (105) in >99% isomeric purity and in 70% yield. Hydroboration then leads to the desired product (Scheme 26). 

Azamacrolide 32e was synthesized from epoxy alcohol 91 (Scheme 6.18). Base-mediated fragmentation of epoxy chloride 91a and alkylation followed by acetylene-zipper reaction gave terminal alkyne 93. Alkylation of 93 and hydrogenation furnished diene 94. Conversion of alcohol into aminoethanol derivative followed by oxidation afforded the acid 94, which on macrolactonization gave azamacrolide (—)-32e (Scheme 6.18). 

Sodium 3-aminopropylamide, a base used to effect the acetylenic zipper reaction, is conveniently prepared from sodium hydride in 1,3-diaminopropane at 70 C without problems associated with foaming, often encountered in previous procedures. ... 

Synthesis.—Further use of the superbase potassium 3-aminopropylamine in the acetylene zipper reaction is reported with the observation that alkyn-l-ols and alkynoic acids can participate in this reaction. Yields are all above 85% and the triple bond may be shifted by up to ten positions (Scheme 62).2. 25o poiy-... 

Procedure A. When the acetylene zipper reaction was complete, the dark-brown reaction mixture was poured into ice water and the mixture was shaken. The organic layer was separated, returned to the flask, then the coupling reaction was carried out as described below. 

In 1975 Brown and Yamashita reported that a triple bond in any position of a straight chain hydrocarbon or acetylenic alcohol, when treated with a sufficiently strong base, could be isomerized exclusively to the free terminus of the chain. The "zipper reaction" thus provides a general solution to the problem of remote functionalization of a long hydrocarbon chain. Isomer-izations along chains of thirty carbon atoms have been achieved. 

Palladium(0)-catalysed coupling of non-conjugated dienes, aryl iodides and stabilized carbon nucleophiles has been developed468. An incredibly high yield (86%) of pentacycle 343 has been obtained from a Pd(0)-catalysed zipper reaction of acetylenic pentaene 342. The reaction is triggered off by a Pd-catalysed cyclization of acetylenic bond and the first olefinic bond469. 

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