SolutionsProtection of alcohols
Exercise 1
Why can an alcohol protected as a THP ether be treated with butyllithium but not with aqueous acid? What drawback does THP have in a chiral alcohol?
The THP ether is an acetal: it has no acidic protons or accessible electrophiles, and it resists bases and organometallics; but in aqueous acid it is protonated, forms the oxocarbenium ion and is hydrolysed. In a chiral alcohol, C2 of the ring is a new stereocentre and a mixture of diastereomers is obtained, which complicates NMR spectra and purification.
Exercise 2
In a triol with a primary, a secondary and a tertiary alcohol, how would you protect only the primary one? And the 1,2-alcohols of a sugar, together?
With a bulky silyl group (TBDPSCl or TBSCl, imidazole, one equivalent, 0 °C) or with trityl chloride and pyridine: steric hindrance means that almost only the primary alcohol reacts. A pair of 1,2-cis alcohols of a sugar is protected as an acetonide with acetone (or 2,2-dimethoxypropane) and an acid; the 1,3 pair of a hexopyranoside (O4 and O6) as a benzylidene acetal.