Selective lithiation of 1,6-dihalohex-1-enes and 1,6-dihalohex-1-ynes

The lithiation of 1-choro- and 1-bromo-6-chlorohex-1-yne (2, 3) with lithium naphthalene in the presence of benzaldehyde in THF at −78 °C leads after hydrolysis with water to the corresponding chloroalkynol (5) resulting from a regioselective lithiation at the alkynylic position. However, the lithiation of 1-chloro-6-iodohex-1-yne (4) under the same reaction conditions and using pentan-3-one as electrophile leads to the corresponding chloroalcohol (6) from the exclusive lithiation at the aliphatic carbon–iodine bond. Double lithiation of compounds 2 and 3 under Barbier conditions allows the isolation of diols (9), whereas the two-step process leads to differently substituted diols 13. The monolithiation of (E)-1-bromo-6-chlorohex-1-ene (14) under the above conditions and using pentan-3-one as electrophile affords a mixture of chloroalcohols 15 and 16, the process being not stereospecific. However, the lithiation of the same starting material with t-BuLi leads exclusively to a bromine–lithium exchange with retention of the configuration, so after treatment with pentan-3-one only compound 16 was isolated. Finally, whereas double lithiation of compound 14 under the conditions for compounds 9 gives the mixture of compounds 18 and 19, the tandem process involving the t-BuLi-promoted bromine–lithium exchange as the first step followed by lithiation under DTBB-catalysed conditions allows the isolation of (E)-diols 19 as the only reaction products isolated.