Possible mechanistic pathways for formation of 14 and 15
involve the intermediacy of the radical-anion 16, which gener-
ates radical 17 by protonation. Reduction of 17 by a second
molecule of SmI2, followed by protonation of the samarium
derivative 18, affords aldehyde 14 (Scheme 4, path a).
The formation of alkenes 21 in this process is consistent
with the involvement of the alkylsamarium intermediate 26,
resulting from R-cleavage of the ketyl radical 24 and
subsequent reduction of radical 25 by a second molecule of
SmI2 (Scheme 6). The intermediate 26 can also be respon-
Scheme 6
Scheme 4
sible for the formation of the alcohol 22, through nucleophilic
addition of oxygen. Diene 23 most probably arises by
spontaneous dehydration of 22.
The results obtained in studies with aldehydes 1 show that
monophenyl or diphenyl substitution on the alkene moiety
does not provide the stabilization required to promote the
carbonyl-alkene reductive coupling process. As a result,
alternative reaction pathways via ketyl radical intermediates,
such as fragmentations and oxidations, are observed.
Although SmI2 has been previously employed to mediate
C-C bond fragmentations,7 to the best of our knowledge,
the reaction documented above represents the first example
of a decarbonylation process taking place in ꢀ,γ-unsaturated
aldehydes promoted by this reagent. It is noteworthy that
this process, reminiscent of the well-known photochemical
Norrish type I reaction, has also been observed when radical-
anion intermediates of ꢀ,γ-unsaturated aldehydes are gener-
ated photochemically using SET-sensitizers.1
Alternatively, oxidation of 18 by nucleophilic addition of
molecular oxygen generates the δ-hydroxyaldehyde 19,
which undergoes intramolecular cyclization to 15 (Scheme
4, path b). This mechanistic hypothesis is supported by the
results of previously described reactions of organosamarium
species with molecular oxygen.3a
To explore the scope of the 3-exo-trig cyclization, the
study was extended to include simple acyclic aldehydes 1,
with monophenyl and diphenyl substitution on the double
bond. However, treatment of aldehyde (E)-1a with SmI2 does
not provide the expected cyclopropanol but rather yields
alcohol (E)-20a (12%), resulting from direct reduction of
the carbonyl group, along with the alkene (E)-21a (16%)
(Scheme 5). Similarly, aldehyde 1b affords alcohol 20b and
A study of the reactivity of the 4-cyanophenyl substituted
aldehyde 27 and ketone 28 was carried out to determine if
the presence of a cyano group attached to the phenyl ring
would provide sufficient activation of the alkene unit to
promote intramolecular reductive coupling. Treatment of 27
and 28 with SmI2 promotes formation of the corresponding
cyclopropanols 29 and 30 in 54% and 23% yield, respectively
(Scheme 7). Therefore, conjugation of the alkene moiety with
a 4-cyanophenyl group promotes the 3-exo-trig cyclization.
The reaction of phenyl ketone 28 also affords the alcohol
31 (19%) resulting from reduction of the carbonyl group.
Interestingly, cyclopropanol 29 was isolated as a 1:1
mixture of Z/E diastereomers, whereas cyclization of phenyl
ketone 29 yields the (E)-cyclopropanol 30 selectively. The
reasons for the lack of diasteroselectivity observed in the
reaction of aldehyde 27 are unclear at this point.
Scheme 5. Treatment of Aldehydes 1 with SmI2
Finally, the reactivity of ketones 32 and 33,8 possessing
two cyano groups directly bound to the alkene unit, was
alkene 21b in 12% and 7% yield, respectively, in addition
to the tertiary alcohol 22 (9%) and the 1,3-diene 23 (11%)
when treated with SmI2.
(7) Williams, D. B. G.; Blann, K.; Caddy, J. Org. Prep. Proc. 2001,
33, 565–602.
(6) (a) Bezzenine-Lafolle´e, S.; Guibe´, F.; Villar, H.; Zriba, R. Tetra-
hedron 2004, 60, 6931–6944. (b) Zriba, R.; Bezzenine-Lafolle´e, S.; Guibe´,
F.; Guillerez, M.-G. Synlett 2005, 2362–2366. (c) Zriba, R.; Bezzenine-
Lafolle´e, S.; Guibe´, F.; Magnier-Boubier, C. Tetrahedron Lett. 2007, 48,
8234–8237.
(8) Efforts made to synthesize the aldehyde analogue (4,4-dicyano-2,2-
dimethyl-3-butenal) by deprotection of its corresponding acetal or thioacetal,
as well as by reduction of methyl 4,4-dicyano-2,2-dimethylbut-3-enoate,
failed.
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Org. Lett., Vol. 12, No. 18, 2010