Synthesis and Comparison of the Reactivity of Allyl Fluorides and ...

11
Chapter One
from quinine and Selectfluor. The product was obtained in an 80 % yield and moderate 40
% ee (Scheme 1.9).
Scheme 1.9 Fluorination of (14) by Quinine/Selectfluor combination
In order to improve upon this, numerous commercially available cinchona alkaloids were
screened. Both DHQB (16) and hydroquinine 1,4-phthalazinediyl diether ((DHQ)2PHAL)
were found to yield the desired fluorinated product as the (R) stereoisomer, with
enantioselectivities greater than 80 % in MeCN at 0 °C. DHQB (16) was used for further
fluorinations simply because it was the cheaper reagent. Various silyl enol ethers were
tested affording the corresponding 2-fluoro indanones and 2-fluoro tetralones in high yields
(71-99 %) and moderate enantioselectivities (42-73%).
1.2.2 Asymmetric Catalysis
Figure 1.8 DHQB (16)
In 2000 the first example of a catalytic asymmetric fluorination of �-ketoesters was reported
by Togni. [28] This work was based on previous studies by Umemoto [29] that had shown that
the reactivity of 1,3-dicarbonyls in the presence of [N-F] + reagents was increased by the
addition of stoichiometric amounts of a Lewis acid, such as zinc chloride. The Lewis acid
significantly accelerated product formation, attributed to the triggering of the enolisation
process. Togni’s group therefore intended to use a chiral non-racemic transition-metal
Lewis acid to promote the enolisation process enabling production of optically active �-
fluorinated 1,3-dicarbonyl compounds.