Synthetic studies of some useful building blocks for preparation of the novel tertiary alkyl fluorides

Bll

73

SYNTHETIC STUDIES OF SOME USEFUL BUILDING BLOCKS FOR PREPARATION OF THE NOVEL TERTIARY ALKYL FLUORIDES

Y. Takeuchi,*

A. Kanada, S. Kawahara, and T. Koizumi

Faculty of Pharmaceutical Sciences,ToyamaMedical&PharmaceuticalUniversity, Sugitani 2630, Toyama 930-01 (JAPAN)

Some synthetic routes to the novel structure of tertiary alkyl fluorides 10 have been developed utilizing the three key compounds, 1,2,and 9. Alkylation of 1 or 2 with Bu$WQ, active olefm} Bu+%H, or R’CHO / Zn proReduction of 3 with LiA& gave p-fluoroduced the diallqlated fluoroester 3. alcohol 4. Halogenation of 4 was accomplished with Ph3P / C& to afford p-fluoro halide 5 which can he transformed

to the target structure

with NaOH yielded the acid 6, which was converted

10.

Saponification

to the corresponding

of 3

chloride

7

by treatment with (COC1)2. Coupling of 7 with Grignard reagent successfully produced the tertiary fluoride 10 0 The chloride 7 could be also converted (NHTP / BrCC13) to a-bromofluoroalkane 8, which was alkylated with Bu3SnR3 to give 10. a-FluoroDirect introduction of the third alkyl group (R3) was also attempted. nitroalkane 9 was obtained from 1 by dealkoxycarbonylation (NaBa or NaOH) followed by alkylation with active olefm. Denitrative alkylation of 9 was achieved with active olefm / Bu3SnH to afford the target structure F

10, although F

F

RdCOOR i

-

R’-&COOR Ii2

i:X=NO,

2:X=E3r

in low yield.

-

R’-&-CHZX

A2

3

4:X=OH 5:X=CIorBr

\ + F l+-&-R~

-

I

NO2

F

F

9

&_p r-l

t Ii3

10

&-Y

6:Y=COOH lb

7:Y=COCl 8:Y=Br