16 Common Reaction Types in Heterocyclic Chemistry
The organolithium species adds to the carbonyl carbon of the DMF, but it is not until aqueous work-up that loss of
dimethylamine reveals the aldehyde (compare with the fi nal step in the Vilsmeier reaction, page 12).
In the reaction of an organolithium reagent with a disulfi de, the nucleophile attacks one sulfur and the relatively weak
S-S bond is cleaved, RS being expelled as a leaving group.
Bromination with 1,2-dibromo-1,1,2,2-tetrachloroethane involves a fragmentation process, as illustrated.
One of the important routes to prepare boronic acids and stannanes, each of which are widely used in palladium(0)-
catalysed processes (Chapter 4), involves the reaction of an organolithium reagent. Thus, reaction with a halotrialkyls-
tannane gives stannanes by displacement of the halide. Similarly, reaction with halotrialkylsilanes generates trialkylsilyl
derivatives. Each of these proceeds via addition of the nucleophile giving an intermediate pentavalent anion and then
elimination of the halide.
Reaction with a trialkyl borate and then hydrolysis produces boronic acids.
Generation of C-metallated heterocycles
There are two important ways in which organolithium intermediates are generated: (i) by metal/halogen exchange
using a heteroaryl bromide (or iodide) and n-butyllithium or t-butyllithium; (ii) by abstraction of a proton using a
strong lithium base such as n-butyllithium, t-butyllithium or lithium di-isopropylamide (LiN(i-Pr) 2 ; LDA), for some
heterocycles directly at favoured positions but also, and importantly, via Directed ortho Metallation (DoM) (see below).
Note: Though alkyllithiums can act in both types of process, LDA is simply a strong base – it will NOT take part in
metal/halogen exchange processes.