128 Purines
C-Metallated purines by direct deprotonation or halogen–metal exchange
After protection of the 9-position, purines can be directly lithiated at C-8, the lithio compounds then reacting with
a variety of electrophiles under normal conditions. Even an adenine derivative containing a free NH 2 can be directly
metallated if a large excess of base is used.
Compounds metallated in the six-membered ring are available via halogen–lithium exchange, but if C-8 is unsub-
stituted, very low temperatures must be maintained to avoid a rapid equilibration to the much more stable 8-lithio
compounds.
Palladium(0)-catalysed reactions
Most commonly, palladium-catalysed substitutions on purines are carried out on a halopurine. Cross-couplings on
6,8-dichloropurines are highly selective for C-6.
Purines with oxygen and amine substituents
Oxy- and amino-purines are potentially tautomeric compounds that exist predominantly as carbonyl and amino
structures, respectively, as indicated at the beginning of this chapter and in line with the situation in simpler hetero-
cycles, such as pyridines.
Oxypurines
Alkylation
The ‘amide’ N-hydrogen in oxypurines is relatively acidic and these compounds can be readily alkylated under
basic conditions, substitution occurring only on nitrogen. This acidity can be readily understood in terms of
the phenolate-like resonance contributor to the anion. Conversely, acylation, sulfonation and silylation occur on
the oxygen.