Preparation of fluoroadamantane acids and amines: Impact of bridgehead fluorine substitution on the solution- and solid-state properties of functionalized adamantanes
Vj. Jasys et al., Preparation of fluoroadamantane acids and amines: Impact of bridgehead fluorine substitution on the solution- and solid-state properties of functionalized adamantanes, J AM CHEM S, 122(3), 2000, pp. 466-473
Functionalized adamantanes are utilized as medicinal therapeutics and a pra
ctical route to novel bridgehead fluorinated adamantylamines and acids incl
uding fully fluorinated 3,5,7-tri-fluoroadamantane-1-carboxylic acid 1 and
3,5,7-trifluoroadamantane-1-amine 2 is described. Potassium permanganate-me
diated bridgehead hydroxylation followed by DAST fluorination was utilized
to sequentially insert bridgehead fluorine atoms. C-13 NMR chemical shifts
of mono-, di-, and trifluoroadamantylamines, acids and carbamates reveal lo
ng-range fluorine-mediated electronic effects within the adamantane framewo
rk, most notably by substrates bearing three bridgehead fluorine atoms. The
impact of multiple bridgehead fluorine substitution on structure (X-ray cr
ystallography) and on physicochemical parameters such as acidity (pK(a)) an
d lipophilicity (log P) which are important for the design of medicinal the
rapeutics is assessed.