Alkyne zipper reaction

The alkyne zipper reaction is an organic reaction of unsaturated hydrocarbons. In the presence of an extremely strong base, a non-terminal alkyne isomerizes to a terminal alkynylide anion:

The reaction is an equilibrium reaction, and is driven by formation (and possibly precipitation) of the terminal anion.^[1] The conversion proceeds for straight-chain alkynes and acetylinic ethers, and provides remote functionalization in long chains.^[2]

Zipper isomerization was first reported by Alexey Favorsky in 1887.^[3]

Equilibrium

The alkyne zipper occurs through repeated isomerizations between an alkyne and an allene. First, the base deprotonates the less-substituted methylene adjacent to the alkyne group, to form an allene anion. The anion reprotonates, but at the other end. Then the base attacks the same lesser-substituted carbon on the allene, catalyzing a similar process to form an alkyne:^[4][1]

Through repetition, the alkyne/allene pseudoparticle can move arbitrarily along an unsubstituted alkane chain. When a terminal alkyne is achieved, the base instead attacks and removes the terminal proton.^[1][4]

A mild acid workup quenches the equilibrium before reprotonating the acetylide anion.^[1][4]

Choice of base

The alkyne zipper reaction requires a base strong enough to deprotonate the final alkyne to form a terminal alkynylide anion salt. Otherwise, the base sets up an isomerization equilibrium, but internal alkynes are thermodynamically favored over terminal alkynes.^[1]

Potash amides, from the reaction of potassium hydride and a diamine, are sufficient, and the state of the art in 1975 was potassium 1,3-diaminopropanide, generated in situ from potassium hydride in 1,3-diaminopropane solvent.^[1] Ethylenediamine cannot replace 1,3-diaminopropane.^{[citation needed]}

Potassium hydride is expensive and hazardous, and a LiCKOR base is an acceptable substitute.^[4] In the synthesis of 9-decyn-1-ol from 2-decyn-1-ol, a mixture of lithium 1,3-diaminopropanide and potassium tert-butoxide affords yields of approximately 85%:^[2]

HO–CH₂C≡C–(CH₂)₆CH₃ → HO(CH₂)₈–C≡CH