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

8
Chapter One
both enantiomers were isolated (10a and 10b). [23] Asymmetric enolate fluorinations were
conducted at -50 ºC, by the addition of 1.2 equivalents of 10a/10b to the preformed
enolates, generated by treatment of 1.5 equivalents of LHMDS with the corresponding
ketones. The 11S,12R,14R isomer (10a) was found to give modest enantioselectivities
ranging from 33-70 % ee. The enantioselective fluorination of the lithium enolate of 2-
methyl-1-tetralone, exhibited the highest asymmetric induction with 70 % ee, 65 % yield.
However, 11S,12S,14R (10b) was very poor in comparison, with enantioselectivities only
ranging from 13-24 % ee. Overall, the enantioselectivities obtained were comparable to
those obtained by the N-fluorocamphorsultams synthesised by Differding [18] and Davis. [20]
1.2.1 [N-F] + Reagents
The development of quaternary N-fluoro ammonium salts based on the cinchona alkaloids
as electrophilic fluorinating agents, was a key development in the area of asymmetric
[24, 25]
fluorination, and was independently reported by the groups of Cahard and Takeuchi.
These are charged [N-F] + reagents and have several advantages over neutral N-F reagents.
Cinchona alkaloids are readily available and can be fluorinated without the need for highly
reactive elemental F2 or FClO3, previously required for the synthesis of N-fluoro-sultams, -
camphorsultams and –amines. Cahard initially synthesisied four [N-F] + reagents, using the
naturally occurring cinchona alkaloids cinchonidine, cinchonine, quinine and quinidine
(Figure 1.7).
Figure 1.7 [N-F] + Enantiopure fluorinating reagents
A one step fluorination based on previous work by Banks [26] was conducted; an equimolar
mixture of the cinchona alkaloid was stirred with Selectfluor in MeCN at 20 °C, with
complete transfer occurring in 20 minutes according to 19 F NMR spectroscopy, and workup
yielding the desired fluorinated product (Scheme 1.6).