SolutionsThe Wittig reaction and related processes
Exercise 1
Propose a synthesis of (Z)-hex-3-en-1-ol, the “leaf alcohol” responsible for the smell of freshly cut grass, by a Wittig reaction. What precautions would you take to make the alkene Z?
Disconnection of the C3=C4 double bond: propanal + the ylide derived from a protected 3-halopropan-1-ol (for example, Ph3P+CH2CH2CH2OTHP Br−), or the propyl ylide + a protected 3-hydroxypropanal. The ylide is non-stabilized, so it gives the Z alkene if the reaction is run without lithium salts (NaHMDS or KHMDS as base), in THF and at low temperature. Finally the alcohol is deprotected with mild acid.
Exercise 2
What product is obtained by treating cyclohexanecarbaldehyde with (a) Ph3P=CHCO2Et in CH2Cl2 and (b) (CF3CH2O)2P(O)CH2CO2Me with KHMDS and 18-crown-6 at −78 °C? Why is the stabilized ylide not useful for olefinating cyclohexanone?
(a) Ethyl (E)-3-cyclohexylpropenoate: the stabilized ylide gives the E alkene. (b) Methyl (Z)-3-cyclohexylpropenoate (Still–Gennari). The stabilized ylide is a poor nucleophile, because the negative charge is delocalized onto the ester carbonyl, and ketones are less electrophilic and more hindered than aldehydes; for ketones the phosphonate carbanion (Horner–Wadsworth–Emmons), much more reactive, is used.