Radical allylation of trifluoromethylated xanthates: Use of DEAD for removing the allyltributyltin excess

Article abstract of DOI:10.1016/S0040-4039(00)02135-3

Radical allylation of trifluoromethylated xanthates allows the preparation of quaternary carbon centers bearing the trifluoromethyl group. An excess of the allyltributyltin reagent must be used in order to achieve satisfactory yields of the adducts. The excess of reagent could be conveniently removed by the use of diethylazodicarboxylate (DEAD).

Full text of DOI:10.1016/S0040-4039(00)02135-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 859–861
Radical allylation of trifluoromethylated xanthates: use of
DEAD for removing the allyltributyltin excess
Jean-Claude Blazejewski,* Patrick Diter, Tadeusz Warchol and Claude Wakselman
SIRCOB, ESA CNRS 8086, Universite´ de Versailles, 45 Avenue des Etats-Unis, 78035 Versailles, France
Received 6 September 2000; accepted 9 November 2000
Abstract—Radical allylation of trifluoromethylated xanthates allows the preparation of quaternary carbon centers bearing the
trifluoromethyl group. An excess of the allyltributyltin reagent must be used in order to achieve satisfactory yields of the adducts.
The excess of reagent could be conveniently removed by the use of diethylazodicarboxylate (DEAD). © 2001 Elsevier Science Ltd.
All rights reserved.
Although numerous methods are now known for the
introduction of a trifluoromethyl group on organic
substrates,1 the elaboration of quaternary carbon cen-
ters bearing this group is not an easy task. Specific
structures have been obtained by cycloaddition reac-
tions or ionic condensations.2 Radical reactions have
been less used in this area.12 Here, we want to describe
our results concerning the intermolecular allylation
of trifluoromethylated tertiary carbon radicals, lead-
classical conditions (KH/THF/CS2, then alkylation by
MeI).23 The tertiary trifluoromethylated radicals have
been formed from these xanthates 3 either by UV
irradiation, or preferably by chemical initiation. Tri-
ethylborane (1 M in hexane) has been useful for the
generation of the radical intermediate at low tempera-
ture. Their allylation by allyltributyltin occurred follow-
ing a radical cycle.24 Several secondary reactions have
been observed: Chugaev elimination leading to trifluo-
romethylated olefins, reduction of the xanthate group
and in some cases rearrangement of the starting O,S-
dialkyldithiocarbonate to an S,S-dialkyldithiocarbon-
ate. In order to minimize these by-products, particular
conditions have been used: reaction at low (−20°C,
entries a and b) or room temperature (other entries),
with a great excess of allyltributyltin (2–10 equiv.) and
without solvent. The results are gathered in Table 1.
ing to trifluoromethylated quaternary carbons
4
(Scheme 1).13
The starting trifluoromethylated alcohols 2 have been
prepared by condensation of the Ruppert Reagent
CF3SiMe3 with the corresponding carbonyl compound
1 in basic medium (1 M Bu4NF/THF).22 Formation of
their xanthate derivatives 3 has been performed under
Scheme 1.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02135-3

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J.-C. Blazejewski et al. / Tetrahedron Letters 42 (2001) 859–861
Table 1. Allyl-trifluoromethyl compounds produced via
Scheme 1
FMRX-CT97.0120, entitled: ‘Fluorine as a unique tool
for engineering molecular properties’.
Entry 1“2a
2“3a 3“4a
References
a
b
c
d
e
52 (CF3 a/b: 96/4)
77 (CF3 a 100%)
92
94
55 (CF3 a/b: 27/73)
7 (CF3 b 100%)
84 (CF3 endo/exo: 96/4)
82 (CF3 ax/eq: 22/78)
56
1. (a) Uneyama, K. J. Synth. Org. Chem. Jpn. 1991, 49,
612–623; (b) McClinton, M. A.; McClinton, D. A. Tetra-
hedron 1992, 48, 6555–6666.
58 (CF3 endo/exo: 2/98) 78
58 (CF3 ax/eq: 77/23)
94
87
92
2. Until now, the Diels–Alder reaction of a trifluoromethyl
bearing dienophile with a non-fluorinated diene has been
the most popular method for this purpose. However, this
kind of reaction either proceeds in low yield (Ref. 3)
unless the fluorinated dienophile is highly activated (Ref.
4) or needs very high pressure (Ref. 5). Among other
methods, the alkylation of stabilized trifluoromethylated
enolates either in a classical way (Ref. 6) or via the
Torgov (Ref. 7) or the Michael reactions (Ref. 8) has met
with some success. More recently, its counterpart, the
pseudo-cationic trifluoromethylation of unfluorinated
enolates was described (Ref. 9). Some functional com-
pounds have been obtained from trifluoromethylated
allylic alcohols by a Claisen rearrangement (Ref. 10). In
the sugar series, a stereoselective SN2% reaction of copper
derivatives with mesylates of similar alcohols has been
reported (Ref. 11).
a Isolated yields (%).
The allylated products were isolated by chromatogra-
phy on silica. Owing to the use of a great excess of
allyltributyltin, several separations were necessary in
the initial experiments to obtain pure products. Various
methods were examined in order to remove the remain-
ing tin reagent. The lithium perchlorate catalyzed inser-
tion of the azo bond in diethylazodicarboxylate
(DEAD) into one allylꢀtin bond of tetraallyltin has
been reported recently.25 We have observed that allyl-
tributyltin is similarly transformed by DEAD to the
metalloene adduct 5 (Scheme 2).
3. Abele, H.; Haas, A.; Lieb, M. J. Fluorine Chem. 1993, 40,
2319–2324.
4. (a) Ansell, M. F.; Nash, B. W.; Wilson, D. A. J. Chem.
Soc. 1963, 3012–3028; (b) England, D. C. J. Fluorine
Chem. 1982, 21, 377–384; (c) Hanzawa, Y.; Suzuki, M.;
Kobayashi, Y.; Taguchi, T. J. Org. Chem. 1991, 56,
1718–1725; (d) Blazejewski, J. C.; Le Guyader, F.; Wak-
selman, C. J. Chem. Soc., Perkin Trans. 1 1991, 1121–
1125; (e) Suzuki, M.; Okada, T.; Taguchi, T.; Hanzawa,
Y.; Iitaka, Y. J. Fluorine Chem. 1992, 57, 239–243.
5. (a) Be´gue´, J. P.; Bonnet-Delpon, D.; Lequeux, T.; d’An-
gelo, J.; Guingant, A. Synlett 1991, 146–148; (b) Iwaoka,
T.; Katagiri, N.; Sato, M.; Kaneko, C. Chem. Pharm.
Bull. 1992, 40, 2319–2324.
Scheme 2.
This condensation is quantitative after a few hours
without catalyst. The metalloene adduct 5 remains on
the silica column when the allylation product 4 is
eluted. Consequently, this procedure allows an easy
removal of the allyltributyltin excess.
6. Ishikawa, N.; Yokozawa, T. Bull. Chem. Soc. Jpn. 1983,
56, 724–726.
Typical procedure:
7. (a) Blazejewski, J.-C.; Dorme, R.; Wakselman, C. J.
Chem. Soc., Perkin Trans. 1 1986, 337–341; (b) Blazejew-
ski, J.-C.; Haddad, M.; Wakselman, C. J. Fluorine Chem.
1991, 52, 353–360.
8. Blazejewski, J.-C. J. Fluorine Chem. 1990, 46, 515–519.
9. Umemoto, T. Chem. Rev. 1996, 96, 1757–1777.
10. (a) Haddad, M.; Molines, H.; Wakselman, C. Synthesis
1994, 167–169; (b) Bouvet, D.; Sdassi, H.; Ourevitch, M.;
Bonnet-Delpon, D. J. Org. Chem. 2000, 65, 2104–2107.
11. Hiraoka, S.; Yamazaki, T.; Kitazume, T. J. Chem. Soc.,
Chem. Commun. 1997, 1497–1498.
12. Cage recombination of radicals generated by photolysis
of trifluoromethylazo derivatives seems the most general
method (Ref. 14). However, it suffers several drawbacks:
the requisite reagent trifluoronitroso-methane is a highly
toxic and expensive gas (Ref. 15); moreover, when possi-
ble, hydrogen abstraction leading to alkenes predomi-
nates over radical recombination (Ref. 16). To our
knowledge, only two examples of the addition of the
electrophilic trifluoromethyl radical (Ref. 18) on electron
Triethylborane (6 mL, 6 mmol, 1 M in hexane) was
added dropwise to a stirred solution of the xanthate 3d
(1.7 g, 5.4 mmol, 77/23 mixture of the axial and equato-
rial isomers) and allyltributyltin (11 mL, 37.8 mmol, 7
equiv.) at room temperature. The progress of the reac-
tion was monitored by TLC (pentane) and the loss of
the yellow color of the solution. After 1 h diethylazodi-
carboxylate (7 mL, 46 mmol) was added to the mixture
and the formation of the metalloene adduct 5 was
followed visually by the fading of the red color of the
azo compound. After 2 h column chromatography of
the reaction mixture (silica gel, pentane) afforded 1.1 g
(4.43 mmol, 82%) of 4d as a colorless oil (22/78 insepa-
rable mixture of the axial and equatorial trifluoro-
methyl isomers).26
Acknowledgements
This work is part of the European TMR program ERB

J.-C. Blazejewski et al. / Tetrahedron Letters 42 (2001) 859–861
861
rich geminally disubstituted alkenes, appeared in the liter-
ature (Ref. 19); but, as expected from the steric require-
ments of the trifluoromethyl group, in both cases the
yield was low. Intramolecular tandem cyclization medi-
ated by a trifluoromethyl substituted double bond has
also been used in the preparation of angularly trifluo-
romethylated indanes (Ref. 20). Two groups (Ref. 21)
independently reported the synthesis of some trifluo-
romethylated five- and six-membered rings by the
intramolecular addition of a secondary trifluoromethyl
bearing carbon radical on a double bond.
21. (a) Watanabe, Y.; Yokozawa, T.; Takata, T.; Endo, T. J.
Fluorine Chem. 1988, 39, 431–434; (b) Morikawa, T.;
Uejima, M.; Kobayashi, Y. Chem. Lett. 1989, 623–624.
22. Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97,
757–786.
23. Barton, D. H. R.; Parek, S. I.; Tse, C.-L. Tetrahedron
Lett. 1993, 34, 2733–2776.
24. (a) Kosugi, M.; Kurino, K.; Takayama, K.; Migita, T. J.
Organomet. Chem. 1973, 56, C11–C13; (b) Grignon, J.;
Pereyre, M. J. Organomet. Chem. 1973, 61, C33–C35; (c)
Keck, G. E.; Enholm, E. J.; Yates, J. B.; Wiley, M. R.
Tetrahedron 1985, 41, 4079–4094.
25. (a) Kinart, W. J.; Tylak, I.; Kinart, C. M. J. Chem. Res.
(S) 1999, 46–47; (b) Kinart, W. J.; Kinart, C. M.; Tylak,
I. J. Organomet. Chem. 2000, 608, 49–53.
13. Presented in part at the 12th International Congress on
Fluorine Chemistry, Durham, July 2000.
14. Go¨litz, P.; de Meijere, A. Angew. Chem., Int. Ed. Engl.
1977, 16, 854–855.
15. Trifluoronitrosomethane is currently available in Europe
26. 1-Allyl-1-trifluoromethyl-4-t-butylcyclohexane 4d had:
calcd for C14H23F3: C, 67.71; H, 9.34%; found: C, 67.59;
H, 9.64%. 19F NMR (282 MHz, CDCl3) l: −69.6 (s, 22%,
cis isomer, CF3 ax); −77.03 (s, 78%, trans isomer, CF3
eq.). 1H NMR (300 MHz, CDCl3) l: 0.86 (s, t-Bu, cis
isomer); 0.89 (s, t-Bu, trans isomer); 1.0 (1H, m, H-4, cis
isomer); 1.15 (1H, m, H-4, trans isomer); 1.31 (m, 4H);
1.5–1.75 (m, 10H); 1.99 (2H, dm, H-2 eq., trans isomer);
2.19 (d, 2H, 3J=7.4 Hz, -CH2-CHꢁ, trans isomer); 2.36
(d, 2H, 3J=7.4 Hz, -CH2-CHꢁ, cis isomer); 5.1 (dd,
from Fluorochem Ltd at 730 # for 5 g.
16. (a) The trifluoromethyl radical is a very good hydrogen
abstractor. See for example: Nonhebel, D. C.; Tedder, J.
M.; Walton, J. C. Radicals; Cambridge University Press,
1979; Chapter 8; (b) Recently, absolute rate constants for
reactions of some perfluoroalkyl radicals (addition to
alkenes and hydrogen abstraction) were published (Ref.
17a,b). The trifluoromethyl radical itself behaves like its
higher homologues (Ref. 17c).
17. (a) Avila, D. V.; Ingold, K. U.; Lusztyk, J.; Dolbier, Jr.,
W. R.; Pan, H.-Q.; Muir, M. J. Am. Chem. Soc. 1994,
116, 99–104; (b) Rong, X. X.; Pan, H.-Q.; Dolbier, Jr.,
W. R. J. Am. Chem. Soc. 1994, 116, 4521–4522; (c)
Dolbier, W. R.; Pan, H.-Q.; Rong, X. X.; Avila, D. V.;
Lusztyk, J.; Ingold, K. U. International Conference on
CFC and BFC (Halons), Shanghai, August 1994.
18. The electrophilic character of some alkyl difluoromethyl
radicals has recently been questioned: Buttle, L.A.;
Motherwell, W.B. Tetrahedron Lett. 1994, 35, 3995–3998.
See also Ref. 17c.
3
3
CH2ꢁ, JH,H-trans=12.5 Hz, JH,H-cis=10 Hz, both iso-
3 3
mers); 5.82 (-CH6 ꢁ, ddt, JH,H-trans=12.5 Hz, JH,H-cis=10
3
Hz, JH,CH =7.4 Hz, both isomers). 13C NMR (75 MHz,
2
CDCl3) l: 21.13 (C3, s, trans isomer); 22.86 (C3, q,
4JC-F=1.6 Hz, cis isomer); 27.3 [C
6
H3, s, trans isomer];
27.45 [C6 H3, s, cis isomer]; 28.12 (ꢁCH-C6 H2-C-CF3, q,
3
3JC-F=2.2 Hz, trans isomer); 30.54 (C2, q, JC-F=1.1 Hz,
trans isomer); 33.98 (C2, q, 3JC-F=1.1 Hz, cis isomer);
32.35 (C
isomer); 41.7 (C1, q, 2JC-F=81.6 Hz, cis isomer); 42.14
(ꢁCH-C
H2, q, 3JC-F=3.3 Hz, cis isomer); 42.6 (C1, q,
2JC-F=83.6 Hz, trans isomer); 46.97 (C4, s, cis isomer);
47.03 (C4, s, trans isomer); 117.7 (ꢁCH2, trans isomer);
118.6 (ꢁCH2, cis isomer); 129.46 (CF3, trans isomer,
1JC-F= 283.4 Hz); 129.85 (CF3, cis isomer, JC-F=285.8
Hz); 133.0 (-CHꢁ, s, trans isomer); 133.6 (-CHꢁ, s, cis
isomer).
6 Me3, s, trans isomer trans); 32.36 (C6 Me3, s, cis
6
19. (a) Cantacuzene, D.; Wakselman, C.; Dorme, R. J.
Chem. Soc., Perkin Trans. 1 1977, 1365–1371; (b) Iseki,
K.; Nagai, T.; Kobayashi, Y. Tetrahedron: Asymmetry
1994, 5, 961–974.
6
6
1
20. Morikawa, T.; Nishiwaki, T.; Kobayashi, Y. Tetrahedron
6
6
Lett. 1989, 30, 2407–2410.
.
.