The relative reactivity of the alcohol and amine in the example just given could be overturned by conducting a reaction under thermodynamic control. In kinetically controlled reactions, the idea that you can conduct chemoselective reactions on the more reactive of a pair of functional groups— carbonyl-based ones, for example—is straightforward. But what if you want to react the less reactive of the pair? There are two commonly used solutions. The first is illustrated by a compound needed by chemists in Cambridge to study an epoxidation reaction. They were able to make the following diol, but wanted to acetylate only the more hindered secondary hydroxyl group.

Treatment with one equivalent of an acetylating agent is no good because the primary hydroxyl group is more reactive; instead, the chemists acetylated both hydroxyl groups, and then treated the bis-acetate with mildly basic methanol (K₂CO₃, MeOH, 20 °C), which reacted only at the less hindered acetoxy group and gave the desired compound in 65% yield.

In other words, start by letting both groups react and then go backwards so the reaction is reversed, but at only one of the two groups. Steric hindrance means that the less favourable reaction (in other words, reaction at the less reactive group) was also less readily reversed.

مواضيع ذات صلة

The Boc protecting group—gastrin and aspartame

The Cbz protecting group—oxytocin

Peptide synthesis

A survey of protecting groups

How to react the less reactive group (II): protecting groups

Chemoselectivity in the reactions of dianions

Competing reactivity: choosing which group reacts

How to oxidize primary alcohols to aldehydes

How to oxidize secondary alcohols to ketones

Birch reduction of arenes

Dissolving metal reductions

Getting rid of functional groups