Codex @codex  0

Disconnect the internal Z alkene by a non-stabilized Wittig reaction:The aldehyde carbon becomes the right-hand internal alkene carbon; the ylide carbon becomes the left-hand one. Both the methyl ester and the remote terminal alkene survive the olefination.

Make the aldehyde from pentanal by Stork enamine reaction: form its pyrrolidine enamine, react at carbon with allyl bromide, then hydrolyse to $\mathrm{OHCCH}(\mathrm{nPr})\mathrm{C}{\mathrm{H}}_2\mathrm{CH}=\mathrm{C}{\mathrm{H}}_2$. The original alpha carbon of pentanal now bears allyl and n-propyl substituents. Control the alkylation to avoid multiple substitutions.

The other branch needs a three-carbon extension of the supplied four-carbon bromo alcohol. Protect the OH of $\mathrm{HO}(\mathrm{C}{\mathrm{H}}_2{)}_4\mathrm{Br}$ as a tetrahydropyranyl ether. Convert the bromide into an organocuprate and add it conjugatively to methyl acrylate:Here the organocopper formula is shorthand for a suitable cuprate preparation, not a claim that an isolated monomer is necessary. The acrylate contributes two methylenes and the ester carbonyl. Remove the THP group, replace the resulting terminal OH by Br, and react with $\mathrm{PP}{\mathrm{h}}_3$ to form $[\mathrm{P}{\mathrm{h}}_3\mathrm{PC}{\mathrm{H}}_2(\mathrm{C}{\mathrm{H}}_2{)}_5\mathrm{C}{\mathrm{O}}_2\mathrm{Me}{]}^{+}\mathrm{B}{\mathrm{r}}^{-}$. Deprotonate adjacent to phosphorus to generate the non-stabilized ylide. This proton is much more acidic than the ester alpha protons, but controlled base stoichiometry and low temperature remain important.

Add the allylated aldehyde under conditions favouring the usual kinetic Z-selective Wittig olefination, and separate any E isomer. The result isThe four-carbon starting alcohol plus the three-carbon acrylate backbone supplies the seven-carbon acid-derived chain; the ester Me gives an eighth carbon. Pentanal plus allyl gives the other eight. The total is sixteen carbons, including the terminal alkene. A two-carbon extension would produce the wrong chain length.

Disconnect the tertiary alcohol at its bond to the alkenyl group. The required carbonyl partner is $\mathrm{MeCOCH}(\mathrm{Me})\mathrm{Et}$; the other partner is an E-configured $\mathrm{PhC}{\mathrm{H}}_2\mathrm{CH}=\mathrm{CH}$ organometallic reagent. This disconnection fixes the alkene geometry before the alcohol is made.

First form the ethyl-side enolate of butan-2-one under equilibrating conditions, then trap it with ethyl iodide and isolate the required monoalkylated ketone:The incoming group is Et: methylation would give a carbon skeleton one carbon too short. Because an unsymmetrical ketone can form two enolates and undergo repeated alkylation, regioisomer separation and controlled conversion are part of this step.

Independently perform a halo-Wittig reaction on phenylacetaldehyde using $\mathrm{P}{\mathrm{h}}_3\mathrm{P}=\mathrm{CHBr}$ and isolate E-$\mathrm{PhC}{\mathrm{H}}_2\mathrm{CH}=\mathrm{CHBr}$ from any geometrical mixture. magnesium insertion in dry ether gives the corresponding vinylmagnesium halide; add the isolated ketone at low temperature and protonate the resulting alkoxide. Addition to C=O preserves the pre-existing C=C geometry:The E alkene and the complete fifteen-carbon skeleton are obtained. No absolute configuration is specified at the newly formed alcohol centre, so an unselected stereoisomeric mixture there is acceptable. An alternative carbon–carbon disconnection is acetylide addition to the same ketone followed by a controlled trans-selective alkyne reduction; the vinyl-reagent route avoids relying on reduction of a tertiary propargylic alcohol.

A Wittig reaction with $\mathrm{P}{\mathrm{h}}_3\mathrm{P}=\mathrm{C}{\mathrm{H}}_2$ that replaces a carbonyl oxygen by $=\mathrm{C}{\mathrm{H}}_2$. On a cyclic ketone it installs an exocyclic methylene without inserting a new ring atom.

Conditions favouring a Z alkene in a Wittig reaction, often using a nonstabilized ylide under kinetic, salt-controlled conditions. Isolation or verification is still required when complete stereoselectivity is not established.