Garst independently attacked this problem with metallic
Mg.9 In agreement with our results, he observed from 1 in
THF 98% of uncylized Grignard reagent and less than 1.5%
of cyclized product. In Et2O, up to 25% of cyclized Grignard
reagent was formed. According to his D-model calculation,
which rationalizes quite satisfactorily the experimental results
observed with alkyl halides, 78% of cyclized Grignard
reagent should have been found in THF. Garst discards the
possibility of adsorbed radicals at the Mg surface, as well
as a very fast geminate reaction between the radical and an
active site. He proposed that within this D-model, if aryl
radicals exist, their lifetime could be about 10-11 s or less,
“a possible but unlikely value”. He concludes that even if
aromatic σ radicals could be formed, a major dianionic
pathway takes place. Therefore Garst proposed that the main
difference between alkyl and aryl halide is the possibility
for the second to reach the dianion stage,10 whereas the first
one is known to undergo a highly dissociative electron
transfer.11 This author pointed out that radical isomerization
(including racemization) during Grignard formation varies,
for a given halide, in the order alkyl > cyclopropyl > vinyl
> aryl. Less radical isomerization would correspond with
an increasing participation of the dianionic pathway.9 Garst
noticed that this trend is consistent with the partial knowledge
presently accumulated about the relative stabilities of RX
radical anions in the series alkyl, cyclopropyl, vinyl, aryl.
One may note, however, that electrochemical experiments12
suggest very short lifetime for the radical anion of aryl
halides bearing the type of substituent (alkyl) present in the
presently studied radical clocks. Exceptionally strong salt
effects10,13 would have to be invoked to extend these very
short lifetimes.
order of magnitude.15 Scheme 2 outlines the synthesis of
radical probes 2a and 2b.
Scheme 2
Our results with metal vapor synthesized Mg*16 are
summarized in Table 1. Radical probes 2a and 2b lead to
Table 1. Reaction of Radical Probes 2a and 2b with Active
Mg* in THF ([RX] ) 0.03-0.04 M)
rel yield (%)c
reactn yield RMgX
entry RX Mg*/RX
T
time
(%)a
(%)b
3
4
1
2
3
2a
2b
2b
4.7
1.3
1.3
rt
1 h
95
91
87
13
-80 °C 1 h
rt
61d
41e
72e
41 (45) 59 (55)
26 (38) 74 (62)
30 min 92
a Yields including phenols for reaction of 2b. Estimated from NMR and
GC analysis using anthracene as internal standard. b Titration with 1,10-
phenanthroline using 1-BuOH/xylene as titrant.18 c Determined by NMR
or GC analysis. See the text for the corrected yield given in parentheses.
d The conversion was 70% according to NMR. e Probably underestimated.
To trap efficiently aryl radicals with short lifetimes, we
decided to effect structural changes in the radical probes,
aiming at an increase of the cyclization rate of 1.
The incorporation of a group stabilizing the rearranged
radical (like a phenyl group) should accelerate at least 10-
fold the cyclization rate.14 Another possibility consists of
replacing the benzylic methylene group by an oxygen atom.
This structural change increases the cyclization rate by 1
the formation of cyclized products 4a and 4b (Scheme 3).
Each experiment was performed twice, and reproducible
yields of products 3a-b and 4a-b were obtained.
Scheme 3
(5) (a) Anteunis, M.; Van Schoote, J. Bull. Soc. Chim. Belg. 1963, 72,
787-796. (b) Jones, L. A.; Kirby, S. L.; Kean, D. M.; Campbell, G. L. J.
Organomet. Chem. 1985, 284, 159-169.
(6) Chanon, M.; Ne´grel, J.-C.; Bodineau, N.; Mattalia, J.-M.; Pe´ralez,
E. Macromol. Symp. 1998, 134, 13-28.
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N.; Beckwith, A. L. J.; Scaiano, J. C.; Ingold, K. U. J. Am. Chem. Soc.
1985, 107, 4594-4596. Corrected value from Garden, S. J.; Avila, D. V.;
Beckwith, A. L. J.; Ingold, K. U.; Lusztyk, J. J. Org. Chem. 1996, 61,
805-809.
Products 3a-b and 4a-b, described in the literature,17
were identified from GC-MS and NMR analysis of the
crude product. Authentic samples of 4a-b were prepared
by reacting 2a-b with Bu3SnH in toluene. The presence of
(8) (a) Ashby, E. C.; Oswald, J. J. Org. Chem. 1988, 53, 6068-6076.
(b) Bodewitz, H. W. H. J.; Blomberg, C.; Bickelhaupt, F. Tetrahedron 1975,
31, 1053-1063.
(9) Garst, J. F.; Boone, J. R.; Webb, L.; Lawrence, K. E.; Baxter, J. T.;
Ungva´ry, F. Inorg. Chim. Acta 1999, 296, 52-66.
(14) (a) Curran, D. P. Synthesis 1988, 417-439. (b) The rate of
intramolecular cyclization of the 5-decyn-1-yl radical is approximately 40
times slower than the cyclization of the 6-phenyl-5-hexyn-1-yl. Peters, D.
G. In Organic Electrochemistry; Lund, H.; Baizer, M. M., Eds.; M.
Dekker: New York, 1991; Chapter 8, p 372. (c) Newcomb, M.; Choi, S.-
Y.; Horner, J. H. J. Org. Chem. 1999, 64, 1225-1231.
(15) Abeywickrema, A. N.; Beckwith, A. L. J. J. Chem. Soc., Chem.
Commun. 1986, 464-465.
(16) (a) Ne´grel, J.-C.; Gony, M.; Chanon, M.; Lai, R. Inorg. Chim. Acta
1993, 207, 59-63. (b) Pe´ralez, E.; Ne´grel, J.-C.; Goursot, A.; Chanon, M.
Main Group Met. Chem. 1998, 21, 69-76.
(10) Boche, G.; Schneider, D. R.; Wintermayr, H. J. Am. Chem. Soc.
1980, 102, 5697-5699.
(11) Andrieux, C. P.; Gallardo, I.; Save´ant, J.-M.; Su, K.-B. J. Am. Chem.
Soc. 1986, 108, 638-647.
(12) (a) Save´ant, J.-M. Tetrahedron 1994, 50, 10117-10165. (b) Pause,
L.; Robert, M.; Save´ant, J.-M. J. Am. Chem. Soc. 1999, 121, 7158-7159.
(13) (a) Boche, G.; Walborsky, H. M. In The Chemistry of the
Cyclopropyl Group; Rappaport, Z., Ed.; Wiley: Chichester, 1987; pp 701-
808. (b) Gonzalez-Blanco, R.; Bourdelande, J. L.; Marquet, J. J. Org. Chem.
1997, 62, 6903-6910 and references therein.
2304
Org. Lett., Vol. 2, No. 15, 2000