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Organic Synteses vol 69 - Paquette L.A.

Paquette L.A., Boecman R.K. Organic Synteses vol 69 - John Wiley & Sons, 1990. - 174 p.
ISBN 0-471-54560-0
Download (direct link): organicsynthesesvol691990.pdf
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18. The product contains about 4% of the 16(3-fiuoroestrone epimer; 1H NMR (360 MHz, CDCI3) 5: 4.76 (dt, J = 50, 8; 16a-H); 19F NMR (CDCI3) 8: -185.3 (dd, J =
50, 22; 16p-F).
19. Identical yields of recovered starting material and product were obtained when Parts В and С were run on 2.5 times the scale. The submitters report obtaining a 78% yield of product, mp 145-149°C (recrystallized from ethyl acetate/hexane after chromatography) containing a small but unspecified amount of its epimer, along with 11% recovered starting material and 12% 2-pyridyl triflate, which is a decomposition product of 1. Anal. Calcd for C19H23O2F: C, 75.47; H, 7.66. Found: C, 75.52; H, 7.81.
3. Discussion
Electrophilic fluorinating agents such as F2,3 CF3OF,4 FCIO3,5 CF3COOF.6 CH3COOF,7 XeF2,8 and CSSO4F9 require the use of special equipment and techniques because of their explosive, toxic, unstable, or hygroscopic nature. N-Fluoroperfluoropiperidine,10 N-fluoropyridone,11 and N-fluoro-N-alkyltoluene-sulfonamides12 are easy to handle, but their low reactivity limits the scope of their
134
applications. More reactive N-fluoroperfluorosulfonamides13 have been recently reported as particularly useful reagents for aromatic fluorination.
N-Fluoropyridinium trifluoromethanesulfonate (triflate) and its derivatives are effective, stable fluorinating agents with varying degrees of fluorinating power.14 The procedure given here represents a general method for preparing substituted N-fluoropyridinium triflates. Triflates 2-4 can be made in good yields in the same manner as 1, although instead of sodium triflate, potassium triflate is required for 2, and lithium triflate for 3 and 4.
The reactivity of the N-fluoropyridinium salts can be adjusted by varying the substituents on the pyridine ring. Triflates 1-4, whose fluorinating power increases in the order 2<1<3<4, are the most generally useful reagents. The most powerful reagent available is 5;1S 6 and 716 recently have been developed as mild, efficient reagents. The reagents are all stable, crystalline materials and thus can be handled routinely. Examples of fluorinations which illustrate their use are given in Table I. The weakest reagent 2 is most suited for fluorinating reactive or easily oxidized compounds, such as carbanions, enamines, and sulfides, whereas the more potent reagents 4 and 5 are preferred for fluorinating aromatic rings. Salt 1 of intermediate
135
reactivity is effective with moderately electron-rich substrates, such as enol alkyl ethers, enol silyl ethers, and activated vinyl acetates.
N-Fluoropyridinium triflate shows high regioselectivity in its fluorinations, as evidenced by the results in Schemes 1 and 2. With steroids 8 and 10, each having two reactive sites, 1 reacts to give exclusively the 6-fluoro steroid 9 and the 16-fluoro steroid 11, respectively. Thus 1 can distinguish between a conjugated and non-conjugated vinyl acetate, and between an enol silyl ether and a conjugated vinyl acetate in its fluorinations. The present procedure for converting the estrone enol silyl ether to the 16a-fluoroestrone also shows that 1 selectively reacts with an enol silyl ether moiety in the presence of an activated aromatic ring.
136
Scheme 1
OAc
1/CHoClo
Reflux, 14 hr 51%
1/CH?Cfe>
Reflux, 1 hr 54%
The fluorination of 12, easily prepared from the corresponding triketo steroid, with an equimolar amount of 1 (Scheme 2) shows the remarkable ability of 1 to distinguish di-substituted from tri-substituted enol silyl ethers. The 9a-fluoro steroid 13 is produced in 51% yield (78% based on recovered triketo steroid) and the combined yield of the other fluorinated products is only 4.6%.17 It thus is apparent that
1 reacts almost exclusively with the trisubstituted enol ether moiety. The new, selective direct fluorination at the 9a-position holds considerable promise as a means to prepare biologically important 9a-fluoro steroids.18
137
Scheme 2
OSiMe3
O
1)1, r.t., 2 hr _CH2CI2 ,
Me3SiO'
2)l-r
o
12
51%
13
With the increasing importance of organofluorine compounds in the development of new materials, pharmaceuticals, and agricultural chemicals, N-fluoropyridinium salts should find extensive use as mild and selective fluorinating agents.
1. (a) Sagami Chemical Research Center, Nishi-Ohnuma 4-4-1, Sagamihara, Kanagawa 229, Japan; (b) Onoda Cement Company, Japan. Present address forT.U.: Daikin Industries, Ltd., Chemical Division, 1-1 Nishi Hitotsuya, Settsu-Shi, Osaka 566, Japan.
2. Specialty Gas Material Data Sheet on Fluorine; Air Products and Chemicals Inc.: Allentown, PA, 1986
3. Purrington, S. T.; Kagan, B. S. Chem. Rev. 1986, 86, 997.
4. Alker, D.; Barton, D. H. R.; Hesse, R. H.; Lister-James, J.; Markwell, R. E.; Pechet, M. M.; Rozen, S.; Takeshita, T.; Toh, H. T. Nouv. J. Chim. 1980, 4, 239.
5. Schlosser, M.; Heinz, G. Chem. Ber. 1969, 102, 1944.
6. Rozen, S.; Lerman, O. J. Org. Chem. 1980, 45, 672.
7. Rozen, S.; Lerman, O.; Kol, M.; Hebel, D. J. Org. Chem. 1985, 50, 4753, and references cited therein.
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