Synthesis of Long‐Chain Dimethylalkyl Methyl Ethers, Important Components of the Epicuticular Wax of Spiders

Long‐chain methyl‐branched alkyl methyl ethers are essential constituents of the cuticle of many spiders, regulating water balance and transporting chemical signals used in species recognition. The synthesis of such compounds, or related hydrocarbons found in insects, is usually time‐consuming and not very efficient, mainly due to the long alkyl chains involved. Herein, new strategies for synthesizing such compounds are evaluated. Negishi sp2–sp3 coupling reactions are first investigated and proceed with yields of 50–70%, even with very long alkyl chains. However, such approaches require the synthesis of vinyl iodides, adding additional steps. While the methyl branches are created early in these syntheses, a late introduction strategy proves more favorable. To facilitate this, chain construction is achieved through the addition of an alkynyl anion to aldehydes, resulting in internal propargyl alcohols that serve as substrates for nucleophilic methylation. Iron‐catalyzed methyl Grignard addition yields methylallyl alcohols, which are subsequently converted into the target compounds through hydrogenation and alcohol defunctionalization. Although this approach is successful for compounds with medium chain length, it fails for very long compounds. Instead, allene formation by nucleophilic addition of the methyl group to propargyl mesylates, followed by hydrogenation, gives good yields and clean target ethers.