Scheme 1 a
a Reagents: (i) Bu3SnH/AIBN or (TMS)3SiH/AIBN.
(trimethylsilyl)silyl radicals (Scheme 1).6a This strategy was
subsequently extended to the use of arenediazonium salts as
alternative precursors to aryl radicals with the principal goal
of avoiding the attendant problems of the undesirable use
of toxic and/or expensive organotin or organosilane reagents.6b
Very recently, our interest in the radical chemistry of
azides prompted us to undertake a study of the intramolecular
reactivity of acyl radicals toward the azido function. To this
purpose, a number of aryl- and alkyl-derived azidoacyl
radicals were generated from the iodothiol azidoesters by
intramolecular homolytic substitution at sulfur, following the
previous methodology reported by Crich. The derived acyl
radicals were found to be interestingly capable of performing
intramolecular five- and six-membered cyclizations onto the
azido moiety, although to an extent dependent upon their
structural features, to give eventually cylized lactams.7
In the course of this study, we became interested in a
search for other thiol ester compounds that might similarly
act as valuable precursors to acyl radicals under reductive
conditions but avoid the need of stannanes or silanes. It thus
occurred to us that, in principle, alkynylthiol esters of type
3 might represent attractive candidates in conjunction with
standard thiols. Indeed, radical addition of a thiol to the
terminal triple bond of 3 was expected to result in regiose-
lective production of an intermediate sulfanylvinyl radical.8
This intermediate, similar to the aryl congener of Crich, was
considered to be presumably capable of performing intramo-
lecular substitution at sulfur to yield thiophene 4 with
concomitant release of an acyl radical (Scheme 2).
Figure 1.
preliminary results of their radical reactions with ben-
zenethiol. The choice of these substrates was essentially
dictated by our additional interest in gaining suitable
information about the intramolecular reactivity of the possible
acyl radicals in the presence of the thiol H-donor rather than
of tributylstannane6a,7 or tris(trimethylsilyl)-silane.6a,7
Compounds 5-7, 9, and 10 were prepared by reacting the
appropriate acid chlorides with the pentynethiol 11 in the
presence of DMAP and compound 8 by direct coupling of
11 with the carboxylic acid in the presence of DCC and
DMAP (Figure 1). Thiol esters 5-8 were obtained in good
to fairly good yields, whereas those containing an azido
function, i.e., 9 and 10, for unclear reasons were achieved
in rather modest yields. The requisite thiol 11 was in turn
readily obtained from commercial 4-pentyn-1-ol through a
three-step protocol involving conversion to mesylate and then
to thiol acetate, followed by eventual treatment with meth-
ylthiolate.9 It is worth noting that the present synthesis of
11 compares favorably with that devised by Crich for
iodothiol 1, which in fact required a rather tedious five-step
procedure starting from much more expensive 2-(2-bro-
mophenyl)ethanol.
Radical reactions of thiol esters 5-10 were normally
performed by adding a benzene solution of PhSH (1.1 equiv)
and AIBN (0.2 equiv) with a syringe pump over 3 h to a
refluxing benzene solution of the appropriate substrate (2
mmol) under a nitrogen atmosphere. The resulting mixture
was refluxed for an additional 2-3 h until virtual disap-
pearance of the starting material and then separated by
column chromatography.
Scheme 2 a
(8) (a) Benati, L.; Montevecchi, P. C.; Spagnolo, P. J. Chem. Soc., Perkin
Trans. 1 1991, 2103. (b) Benati, L.; Capella, L.; Montevecchi, P. C.;
Spagnolo, P. J. Chem. Soc., Perkin Trans. 1 1995, 1305. (c) Benati, L.;
Capella, L.; Montevecchi, P. C.; Spagnolo, P. J. Org. Chem. 1994, 59, 2818.
(d) Benati, L.; Capella, L.; Montevecchi, P. C.; Spagnolo, P. J. Org. Chem.
1995, 60, 7941.
(9) Thiol 11 has recently been prepared from 4-pentyn-1-ol by means
of a similar three-step procedure, but no experimental details have been
furnished (see: Journet, M.; Rouillard, A.; Cai, D.; Larsen, R. D. J. Org.
Chem. 1997, 62, 8630); compound 11 has also been previously prepared
from 1-chloro-4-pentyne through hydrolysis of the derived thiuronium salt
(see: Dupuy, C.; Crozet, M. P.; Surzur, J. M. Bull. Soc. Chim. Fr. 1980,
Part 2, 353).
a Reagents: (i) R′SH/AIBN.
In this paper, we report the preparation of the novel
alkynylic thiol esters 5-10, shown in Figure 1, as well as
(6) (a) Crich, D.; Yao, Q. J. Org. Chem. 1996, 61, 3566. (b) Crich, D.;
Hao, X. J. Org. Chem. 1997, 62, 5982.
(7) Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.;
Strazzari, S.; Zanardi, G. Org. Lett. 2002, 4, 3079.
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Org. Lett., Vol. 5, No. 8, 2003