Electrophilic fluorination of diazoketones

摘要

1224 J.C.S. Perkin I Electrophilic Fluorination of Diazoketones By Jacques Leroy and Claude Wakselman,' C.N.R.S.-C.E.R.C.O.A. 2 rue Henry Dunant, 94320 Thiais, France Fluorination of diazoketones with trifluoro(f1uoro-oxy) methane produces mainly a mixture of aa-difluoroketones and a-fluoro-cc-trifluoromethoxy ketones. The initial electrophilic attack on the diazo group is followed by nucleophilic attack by F-or CF,O-. In the case of diazocamphor a rearrangement occurs and leads to the formation of a fluorotricyclanone. The use of molecular fluorine can also lead to acc-difluoroketones. FLUORINATIONof organic compounds by molecular fluorine is rendered particularly difficult by the high re- activity of this reagent which can break carbon-carbon bonds. Less drastic and more selective fluorinating agents such as trifluoro (fluoro-oxy)methane (CF,OF) are commonly used.There has been a controversy over the ionic or radical nature of the action of trifluoro-(fluoro-oxy)methane on double bonds. The observed transposition reactions and solvent participation favour an ionic mechanism.l However, the fluorination of halogenated olefins by trifluoro(fluoro-oxy)methane is neither regio- nor stereo-selective : this would rather suggest a radical mechanism.2 The ionic character of the reagent is best revealed by its action on polar substrates. Thus, we have studied its reactivity on primary and secondary diazoketones. These compounds are known to be particularly sensitive to electrophilic attack by halogens and pseudo halogen^.^ This study shows that the reagent behaves like a pseudo-6+ +a-halogen4 and its polarization is F-OCF,.In the presence of a radical inhibitor (such as nitrobenzene) ,5 the reaction is not substantially modified. In the case of 3-diazobornan-2-one (3-diazocamphor) (7),there is evidence for a transposition reaction with an ionic intermediate. Reactions were carried out at -70 "C in an inert solvent (chlorotrifluoromethane) and both awdifluoro and cc-fluoro-a-trifluoromethoxy ketones were always isolated. Nucleophilic attack of the polarized diazo- alkanone (1) on the fluorine atom bonded to oxygen is followed by nucleophilic attack by CF,O-or F-(there is an equilibrium, CF,O- COF, +F-) on an inter- mediate such as (2) or the resultant a-fluoro-a-oxo-carbenium ion (2') (Scheme 1).(a)D. H. R. Barton, L. S. Godinho, R. H. Hesse, and M. M. Pechet, Chem. Comm., 1968, 804; (b) D. H. R. Barton, L. J. Banks, A. K. Ganguly, R. H. Hesse, G. Tarzia, and M. M. Pechet, ibid., 1969, 227; (c) D. H. R. Barton, R. H. Hesse, G. P. Jackman, L. Ogunkoya, and M. M. Pechet, J.C.S. Perkin I, 1974, 739. K. Johri and D. D. Des Marteau, Third Winter Fluorine Conference, St.Petersburg, Florida, 1977. Reactions of Primary Diazoketones with Trifluoro-(fluoro-oxy)methane.-For primary diazoket ones , the conversion is generally total (with ca. 1.5 equiv. of CF,OF), however the yields of isolated products are low owing to their difficult separation by methods other than R'CO ~EEN R'CO OC5 bsol;c' 'c' (3)/bsol;RZ F 4 R'CO (1 1 a; R' = Ph, R2=H b; R' = CEH11 R2=H C; R' = Bu' , R2= H e; R'R~= d; R' =PhCH2, RZ=H SCHEME1 g.1.c.In the cases of diazoketones (lb-d), the reaction leads to the formation of ketones (3) and (4) as well as to two different epoxides (5) and (6), which have been isolated for cases (lb and c) and/or characterized, espec- ially by n.m.r. spectrography. Compounds of type (5) have two vicinal fluorines. Compounds (6) have vicinal fluorine and trifluoromethoxy groups. The n.m.r. spectra of both types of epoxides display geminal H-F coupling constants (85Hz) as observed in monofluorinate- epoxides6 These compounds can result from an attack (a) 0. 0. Orazi, R.A. Corral, and H. Schuttenberg, J.C.S. Perkin I, 1974, 2087 and references therein: (b) G. A. Olah and J. Welch, Synthesis, 1974, 896 and references therein. Preliminary communication, C. Wakselman and J. Leroy,J.C.S. Chem. Comm., 1976, 611. ti D. H. R. Barton, R. H. Hesse, R. E. Markwell, M. M. Pechet, and H. T. Toh, J. Amer. Chem. SOC.,1976, 98, 3034. E. Elkik and M. Le Blanc, Bull. SOC.chim. Francs, 1971, 870. of the trifluoromethoxide anion or fluoride anion on the carbonyl group of the a-oxodiazonium ion (2) (Scheme 2). (6) X = OCF3 SCHEME2 Since the reaction leads to one isomer only, it is not likely that a genuine a-oxocarbenium ion (2rsquo;) is formed. If that were so, the reaction would yield a mixture of cis- and trans-isomers for each epoxide.Asymmetric induction seems more likely, either on (1) and/or (2). A four-or six-centred concerted transfer of trifluoro- (fluoro-oxy)methane (CF,O-F or F-CF,O-F) to the diazoketone cannot be completely discarded. The stereochemistry of the two types of epoxides could not be determined from the proton-fluorine or fluorine- fluorine coupling constants. However, in the case of epoxides (6), the value of the fluorine-fluorine coupling constant increases with the size of the substituent R. This would favour fluorine and trifluoromethoxy cis relative to the epoxide plane. The coupling would be through space and would increase with the steric inter- action between R and the trifluoromethoxy group. The percentages of the various fluorination products measured by 19F n.m.r.spectrography are listed in Table 1. TABLE1 Product distribution for the addition of trifluoro-( fluoro-oxy) methane to primary diazoketones( 1) Product (yo) Substratc (3) (4) (5) (Gj ( la) 42 58 0 0 (11)) 25 43 20 12 a ( 1c) 27 32 30 11 (1c) 29 32 25 14 (Id) 24 40 27 9C a With 0.1 cquiv. PhNO, added. a Isolated impure. Not isolated. Reaction of Diazo bornan-2-one with Trijluoro (fluoro-0xy)methanc.--The acid-catalysed decomposition of secondary a-diazoketones, and particularly of 3-diazo- bornan-one (7),has shown that the products depend (i) on the structure of the diazonium ion (2), (ii) on thermodynamic versus kinetic control of the formation of the epimeric diazonium ions, and (iii) on the solvent system in which the reaction takes place.It is generally accepted that there is no a-oxocarbenium ion (2rsquo;) formed by loss of nitrogen. On the contrary, there is concerted loss leading to the formation of different non-classical ions according to whether the diazonium ion (2) is of exo-or endo-type.rsquo; Thus, there are many products corresponding to the various sites which can be attacked by the counterion. However, in the case of the reaction of 3-diazobornan-2-one with trifluoro(fluoro-oxy)-1225 methane, the composition of the crude product is simpler as shown by its 19Fn.m.r. spectrum. Never-theless, two signals which are probably trifluoromethoxy resonances and are not associated with fluorine reson- ances have not been assigned.The other signals are from three compounds which have been isolated by g.1.c. in the ratio 31 : 27 : 42 (the total yield with respect to diazobornan-2-one is SOY0). The structure of these compounds has been determined mainly by n.m.r. spectroscopy. The large value for the fluorine-fluorine coupling constant in 3,3-difluorobornan-2-one (8) is an unambiguous indication of geminal difluoro substitution. At 250 MHz, the most shielded methyl resonance v W OCF, I (91 (10) (6 1.22) is a doublet (J 5.5 Hz). This is probably the 8-methyl resonance with through-space coupling with the exo-fluorine atom. The endo-fluorine resonance is a singlet and this nucleus is therefore not coupled with any of the neighbouring protons such as 4-H.Compound (9) is a mixture of two isomers in the ratio 66 : 34. The 19Fn.m.r. spectrum of this mixture displays resonances for the two trifluoromethoxy groups and also for the corresponding fluorine atoms substituted on a tertiary carbon atom. There are no lH n.m.r. reson-ances with chemical shifts up to 6 2.8; this excludes a CH(OCF,) group. The 19Fn.m.r. spectrum of 2-fluoro-4,7,7-trimethyl-tricycl02.2.1.O~~~hept-3-one(10)has a triplet to high field of CFCl, 6 234 (CDCl,). Its #H n.m.r. spectrum (CDC1,) displays distinct signals for the three methyl groups. One at high field is a doublet. Two resonances, 6 1.94 and 2.33, are both doublets (respectively J 2 and 10.6 Hz). At 250 MHz, this pattern is unchanged.By heteronuclear decoupling of the fluorine atom, all the doublets become singlets. As in the case of 3,3-difluoro- bornan-2-one (8),it is probable that the fluorine atom is coupled through space with the 8-methyl group protons. Furthermore, 1-and 6-H appear to be equivalent (8 2.33); the same applies to exo-5- and endo-5-H (6 1.94). These nuclei are coupled only to fluorine. The structure of compound (10) was confirmed by its 13C n.m.r. spectrum which exhibits characteristic cyclopropane I3C-F couplings. The reaction of trifluoro(fluoro-oxy)methane with 3,3- difluorobornan-2-one can be compared with that of L. Friedman, lsquo; Carbonium Ion Formation From Diazonium Ions rsquo; in lsquo; Carboniums Ions,rsquo; Wiley, New York, 1970, p. 692. hydrogen chloride in an aprotic solvent where the re- arrangement is limited to the formation of a tricycliccompound.8 The formation of the geminal compounds (8) and (9) can be explained in terms of an SN2 displace-F c*(91+:(12) ment of nitrogen by the counterions CF,O- or F-acting on the a-fluorodiazonium ions (12).The dispersion of the counterions in the medium is limited by use of a non-polar solvent. Cyclopropanation, which leads to the formation of product (lo),results from the loss of a proton from one of the ions (13) resulting from rearrangement of the amp;;-Nz+amp; (13) - (lo) ex0 -(12) exo-diazoniuni ion (12). In the case of ion (12), the loss of nitrogen is favoured by assistance of the C(4)-C(5) bond which is antiparallel to the C(3)-N bond.Reactions of FIuorine with Diazoketones.-A survey of the literature shows that nonselective fluorination would be expected together with polyfluorination and carbon-carbon bond breaking. However, although elemental fluorine can have a regiospecific action on saturated carb~n,~.~ earlier work shows that alkyl chains and phenyl are inert under similar conditions.1deg; At -70 "C, molecular fluorine diluted by an inert gas reacts with aliphatic diazoketones (la-c) in chloro- trifluoromethane solutions. As expected, the reaction yields the corresponding a-difluoro-ketones. The 19F n.m.r. spectrum of the crude products shows clearly the resonance of geminal fluorines among numerous, un-identified fluorine signals. Difluoro-ketone (4c) was isolated in low yield (15).ButCOCHN, --amp; ButCOCHFz +fluorinated by-products (4c) Under the same conditions, 3,3-difluoronorbornan- one (8)was fluorinated to give a complex mixture from which compounds (8) and (10) could be isolated in the ratio 70 :30. Nevertheless, yields remained low. conc~usion, the study of the reaction of trifluoro-(fluoro-oxy)methane with a-diazoketones shows that an ionic mechanism is involved. This type of mechanism is 1)robably predominant when trifluoro(fluoro-ox~)-methane is in the presence Of a polarised substrate. M. Hanack and J. Dolde, Tetrahedron Letters, 1966, 321. 9 D. H. R. Barton, R. H. Hesse, R. E, Markwell, M. M. Pechet, and S. Rozen, J.Amer. Chem,.SOC.,1976,98, 3036. J.C.S. Perkin I The mode of reaction of molecular fluorine is not very well knownI9J1 but it is shown here that fluorine reacts with diazoketones as an electrophile. EXPERIMENTAL IH (60 MHz; Me,Si as internal standard) and l9Fn.m.r. spectra (56.4 MHz; CFCl, as internal standard) were TABLE2 N.m.r. data (6; CDCl,) for fluorinated products obtained from primary diazoketones (I) Product 'H 19F (3a) 6.34 (1 H, d, JH,F 56 60.2 (3 F, d, JF,F 4.9 Hz,CHF), 7.23-Hz, OCF,), 135.5 8.12 (5H, m, Ph) (1 F, dqt, JF.H 0.9 Hz, CHF) (44 6.23 (1H, t, JH.F 53 153.7 (dt, Jp,H 1.0 Hz, Hz, CHF,), 7.2-CHF,)8.17 (511, m, Ph) (3b) 0.48-2.52 (10 H, m), 60.7 (3 F, d, JF.F 4.6 2.82 (1H, m), 5.76 Hz, OCF,), 138.2 (1 H, d, JH.Y 56.0 (1 F, dqd, JF.H 1.6 Hz, CHF) Hz, CHF) (4b) 0.57-2.53 (10 H, m), 128.6(dd, JF,H 1.2 Hz, 2.82 (1 H, m), 5.68 CHF,)(1H, t, JH.F 53.6 Hz, CHF,) (34 1.28(9H,JHJO.~HZ,61.5(3F,d,J~,~4.7 CH,), 6.08 (1H, d, Hz, OCF,), 137.6 JH.F 56.5 Hz, CHF) (1 F, dqrn, CHF) (4c) 1.28 (9 H, t, JH,F 0.75 126.8 (d, CHF,)Hz, CH,), 5.98 (1H, t,JH,F 53.6 Hz, CHF2)(3d) 8.89 (2 H, d, JH,F 1.5 60.0 (3 F, d, JF,F 4.9 Hz), 5.89 (1H, d, Hz, OCF,), 137.5 JH.F 56 Hz, CHF), (1F, dqt, CHF)7.2 (5H, Ph) (4d) 3.82 (2 H, t,JH,F 1.1 127.6 (dt, CHF,)Hz,CH2),5.58(1H, t. JH.F 53.6 Hz,CHF,), 7.2 (5H, Ph)(5; R = c6~~ll)0.58-2.63 (11H, m), 152.0 (1 F, ddd, J ~ , ~ 5.31 (1H,dd, JH.F 35.3 Hz, JF,H 12.0 84.0, 2.2 Hz, CHF) Hz, CFR), 163.5 (1F, dd, CHF) (6; R = C6H1,p 5.48 (d, 1H.p 84.0 Hz, 54.8 (3 F, d, JF.F 3.9 CHF) Hz, OCF,), 163.0 (1F, dqd, JF.H 1.7 Hz, CHF) (5; R = But) 1.07 (9 H, d, JH,F 0.8 155.5 (1F, dm, JF,F Hz, CH,), 5.45 (1 H, 36.0 Hz, CFR), 163.0 dd, JH,F 85.0, 2.5 (1 F, dd, CHF)Hz, CHF) (6; R = Bu') 1.04 (9 H, S, CHJ, 5.48 53.6 (3F, d, JF.F 8.8 (1H, d, JH.F 85.0 Hz, OCF,), 163.1 Hz, CHF) (1F, dq, CHF) a Isolated impure.recorded with a JEOL C-60 HL instrument equipped with JEOL JNM-SD-HC heteronuclear spin decoupler. Spectra at 250 MHz were obtained with a Cameca spectrometer. I3C N.m.r. spectra were run at 20 MHz with a Varian CFT-20 spectrometer. 1.r. spectra were recorded on a Perkin-Elmer 457 spectrometer for solutions in carbon tetrachloride. Mass spectra were obtained at 70 eV on an A.E.1.-MS 30 double beam apparatus.Preparative g.1.c. were performed with a Varian Aerograph nlodel 920 chromatographcolumns~ Apiezon (lB~)-Cl~romosorbWAW solso (2 m) ; SE30 (30)-Cl~romosorb PAW 46/60 (3 m) ; and 10 R.H. Merritt and F. A. Johnson, J. Org. Chem., 1967, 32, 416. l1 R. Breslow, R. J. Corcoran, B. B. Snider. R. J. Doll, P. L. Khanna, and R. Kaleya, J. Amer. Chem. SOC.,1977, 99, 905. 1978 EGS ( 15~o)-CliromosorbWAW 60/80 (2 nij ; He as carrier gas. B.p.s were determined by Siwoloboff's method on a Biichi apparatus and 1n.p.s on the same apparatus. Tri-fluoro(fluoro-oxy)methane was supplied by Soci6t6 des Usines Chimiques de Pierrelatte. Aliphatic diazoketones were prepared from the corresponding acid chlorides by Eistert's method and 3-diazobornan-2-one by the method of Cava et a1.12 Fhorinations of Diazoketones wit?L Trifluoro(fEuoro-ox~y)-methane.-General procedure.Diazoketone ( 15-65 nimol) in trichlorofluoromethane (150 ml) for (la), chloroform (50 ml) was added to maintain solubility at low tem-perature at -70 "C was stirred while an escess (1.5 equiv.) of trifluoro(fluoro-oxy)methane diluted to 20y0 with nitrogen was bubbled in. The mixture was allowed to warm to room temperature under nitrogen. The solution was neutralised with a 5 sodium hydrogencarbonate solution and extracted with trichlorofluoroniethane. The combined extracts were washed with brine and dried (MgSO,). After rotary evaporation or distillation at atmospheric pressure case (lc), the resulting mixture was separated by preparative g.1.c.after bulb-to-bulb distillation under reduced pressure. u-Fluoro-a-trifluoronaethoxyacetop~~enone(3a) (yield 10 from acid chloride) had b.p. 182-183" at ca. 760 Torr; wmnx. 1722-1 702 cm-l (Found: C, 48.75; H, 2.8; F, 34.2. C,H,F402 requires C, 48.65; H, 2.7; F, 34.2); m/e 222 (amp;I+).a,a-Dzfluoroacetophenone (14) had b.p. 185" at ca. 760 Torr; wmax. 1714-1 701 cn-l (Found: C, 61.7; H, 3.9; F, 24.35. C,H,F20 requires C, 61.55; H, 3.85; F, 24.35); m/e 156 (M+). CyclohexylfEuoro(tri-fluoromethoxy)methyl ketone (3b) (9) had b.p. 172-173" at ca. 760 Torr; wnlax. 1735 cm (Found: C, 47.8; 13, 5.45; F, 33.05. C,H12F,0, requires C, 47.35; H, 5.3; F, 33.3) ; wt/e 228 (M+).Cyclohexyl difluoromethyl ketone (4b) (14) had b.p. 168" at ca. 760 Torr; w,,,. 1 733 cm-' (Found: C, 59.3; H, 7.5; F, 23.55. C,H12F20 requires C, 59.25; H, 7.45; F, 23.450/,); m/e 162 (M+). DifEuoro-methyl t-butyl ketone (4c) (12) had b.p. 103-104" at ca. 760 Torr; w,,,~~.1 740sh, 1 736~11,and 1 723 cm-l (Found: C, 53.0; H, 7.15; F, 27.9. C,H,,F,O requires C, 59.25; H, 7.4; F, 27. 9yo), FZuoro(trifluoromethoxy)methylt-butyl ketone (1176) had b.p. 116-117" at ca. 760 Torr; wmaX. 1744-1 726 cm-1 (Found: C, 41.65; H, 4.95; F, 37.5. C,H1,F40, requires C, 41.6; H, 5.0; F, 37.6). 1,2-Di-fluoro-l-t-butyloxiran (5;R = But) was formed in 6 yield (Found: C, 52.3; H, 7.2. C,H,,F,O requires C, 52.95; H, 7.40/,).2-Fluoro-l-t-butyl-l-trifluoromethoxyoxiranwas formed in 5 yield (Found: C, 41.4; H, 5.15. C,H,,F,O, requires C, 41.6; H, 5.0). Benzyl fluoro(trifluoro-methoxy)methyl ketone (3d) (6) had b.p. 197" at ca. 760 Torr; m.p. 78-79"; w,,,. 1754 cm-l; m/e 236 (M+). Benzyl clifluoromethyl ketone ($yo),b.p. 203" at ca. 760 Torr; w,,,. 1 754 cm-l; na/e 170 (M+). Reaction of 3- Diatobornan-2-one wit?L Trifiuoro(fEuoro-oxy)-metha~e.-3-Diazobornan-2-one (7) (3.6 g, 20 mmol) was treated with trifluoro(fluoro-oxy)methane (1.5 equiv.) as l2 M. P. Cava, R. L. Litle, and D. H.Napier, J. Org. Chem . 1958, 80, 2257. 1227 described above. The components of the crude product (oil; 4.2 g) were separated by g.1.c. on an EGS column, giving in order of elution 3-fluoro-3-trifluoromethoxybornan-2-one (9) (0.82 g, 16) as a mixture of epimers (liquid), wmX.1782 cm-l; GH(CDCl,) 0.92-1.18 (9 H, CH,) and 0.6-3.0 (5 H, m, CH and CH,); GF(CDC1,) one epimer (66) 52.8 (3 F, dd, JF,F 9.4, JF,H 1.8 Hz, OCF,) and 113 (1 I?, m, W1,2 29.6 Hz, CF); other epimer (34) 53.7 (3 F, dd, J$-,F 9.5, JF,H 1.5 Hz, OCF,) and 115.4 (1 F, q, CF) (Found: C, 51.7; H, 5.5; F, 29.85. CllHl,F,O, requires C, 51.95; H, 5.55; F, 29.9); m/e 254 (M+);3,3-diJuoro-bornan-2-one (8) (purified by sublimation at 0.01 Torr) (0.71 g, 19yo), m.p. (sealed capillary) 175-177"; w,,,~~. 1 775 c1n-l; GH(CDC1,) (250 MHz) 0.6-2.6 (5 H, m, CH and CH,), 1.22 (3 H, d, JH,F~~~6 Hz, CHJ, 1.23 (3 H, S, CHJ, and 1.30 (3 H, s, CH,); GF(CDCl,) 109.3 (1 F, dm, 1F.F 280, W112 18.3 Hz, F exo) and 115.5 (1 F, d, F endo) (Found: C, 63.9; H, 7.3; F, 20.5.C,,,H1,F,O requires C, 63.8; H, 7.5; F, 20.2) ; m/e 188 (M+); and 2-3uoro-4,7,7-trimethyl-tricyclo2.2. 1.02yBhefitan-3-one (10)(purified by sublimation at 0.01 Torr) (0.86 g, 25y0),m.p. (sealed capillary) 142-144"; w,,,. 1 769 cm-l; GE(CDCl3) 0.81 (3 H, d, JH,F 1.4 Hz, CH,), 0.93 (3 H, S, CH,), 1.00 (3 H, S, CH,), 1.94 (2 H, d, 1R.F 2 Hz, exo-and endo-5-H), and 2.33 (2 H, d, JHmF 10.6 Hz, 1-and 6-H); Gn(C,D,) 0.52 (3 H, s, CH,), 0.63 (3 H, d, JH.F 1.3 Hz, CH,), 0.76 (3 H, S, CH,), 1.46 (2 H, d, JH.z-1.9 Hz, exo-and endo-5-H), and 1.87 (2 H, d, Jrr,p10.6 Hz, 1-and 6-H); GF(CDC1,) 234 (t, JF,n 10.6 Hz, CF); 6C(c,n,; Me,Si) 6.02 (s, C-lo), 19.71 (s, C-8 or -9), 20.97 (s, C-9 or 4, 24.3 (d, Jc,~7.1 Hz, C-1 or -6), 35.9 (s, C-5), 36.5 (d, JCPF 6.0 Hz, C-6 or -I), 44.1 (s, C-7), 49.6 (s, C-4), 82.6 (cl, Jc.F 270.5 Hz, C-a), and 186.5 (d, Jc.17 8.1 Hz, C-3) (Found: C, 71.3; H, 7.8; F, 11.75.CIoHl,FO requires C, 71.4; H, 7.75; F, 11.3); m/e 168 (42y0, M+), 153 (22, M -CH,'), and 125 IOO, M -(CH, + CO)+. Reaction of l-Diazo-3,3-dimethylbutan-2-onewith Fluorine. -Diazoketone ( lc) (80 mmol) in chlorotrifluoroniethane (300 ml) was stirred vigorously at -65 "C while an excess of fluorine (ca. 1.5 equiv.) diluted to lo:/, in nitrogen was passed through until the solution became colourless. The mixture was purged with nitrogen, allowed to warm to room temperature, and then worked-up as described for trifluoro(fluoro-oxy)methane. Distillation gave the ketone (1.5 g, 14). Reaction of 3-Diazobornan-2-one with Fluorine.-Diazo-ketone (7) (3.7 g, 20 mmol) treated by fluorine as described above gave an oil (4.1 g) which was chromatographed on Merck silica gel 60 (benzene as eluant). An unidentified oil was first eluted, then 3,3-difluorobornan-2-one(8)followed by tricyclanone (10). Compounds (8) and (10) were purified by repeated preparative g.1.c.-sublimation and identified by comparison with compounds obtained from trifluoro(fluoro-oxy) methane. We thank Dr. J. Bensoam and Mr. G. Vignal, I.R.C.H.A., Vert-le-Petit, for performing fluorinations with elemental fluorine and Dr. G. de Villardi for linguistic assistance. 7/2255 Received, 28th December, 19771