Communications
Table 3: Cyclic sulfinates from an alkyl radical.
We finally examined the cyclization of alkyl sulfinamide 7
(Scheme 1). The reaction still worked and cyclic sulfinamide 8
could be isolated in good yield (83%). However, some
reduced material was also obtained. As was expected from
Entry Precursor R1 R2 Conditions[a] Product, yield [%] trans/cis
1
2
3
4
5
6
7
8
9
5a
5a
5b
5b
5c
5c
5d
5d
5e
5e
H
H
H
H
H
H
H
H
A
B
A
B
A
B
A
B
6a, 85
6a, 65
6b, 60
6b, 69
6c, 85
6c, 84
6d, 70
6d, 63
6e, 85
6e, 99
–
–
Me
Me
tBu
tBu
Me Me
Me Me
66:34
63:37
100:0[b]
100:0
–
–
Scheme 1. Cyclization of alkyl sulfinamide 7.
nP
nP
r
r
H
H
A
B
69:31
63:37
[c]
10
the previous experiments, lowering the temperature gave only
reduced product 9. This finding represents a noticeable
difference compared with the benzofused sultine case, and
shows that the formation of cyclic alkyl sulfinamides is a
slower process.
[a] Conditions A: Bu3SnH, AIBN (10 mol%), benzene, D; B: TTMSS, V-
501 (25 mol%), benzene, D. [b] The product could not be separated from
AIBN by-products. The yield was calculated relative to 1,3,5-trimethox-
ybenzene as internal standard. [c] AIBN was used.
In conclusion, we have devised an efficient, general access
procedure for cyclic sulfinates and sulfinamides based on
homolytic substitution at the sulfur atom. Both purely alkyl
and benzofused families of compounds could be accessed.
The cyclization of a prochiral radical proceeded with varied
stereochemical outcomes, which depended on the size of the
incoming radical. Biologically active sultines were quickly
prepared by this method, which opens the way to the synthesis
of a vast library of analogues. We are currently assessing the
process at the stereogenic sulfur atom, with a view to
preparing enantiopure sultines and cyclic sulfinamides. Prog-
ress along this route will be presented in due course.
the other methods we tried led to the loss of the products. The
yields reported indicate the calculated amount of desired
product present in the isolated mixture. Tin by-products
(usually 10–30 mol%) were also present. Moreover, some of
the products could not be separated from the AIBN residues.
We thus changed to TTMSS as mediator and V-501 (azobis-4-
cyanovaleric acid) as initiator (conditions B), because we
anticipated that separation from the by-products could be
achieved readily, either upon aqueous workup or by filtration
on silica. This change proved rewarding, as the sultines were
obtained in similar yields with no traces of either mediator or
initiator residues (Table 3, entries 2, 4, 6, 8, 10).
Received: September 22, 2005
When a prochiral radical was cyclized, the trans diaste-
reomers were favored (Table 3, entries 3–6, 9, 10), as evi-
denced by comparison with known products.[38] The selectivity
depends on the size of the substituents. Methyl and propyl
groups typically gave a 2:1 selectivity, while the bulky tert-
butyl group led to the formation of a single diastereomer,
which we assumed to be a trans isomer by analogy with the
methyl case.
Noticeably, the method still worked smoothly with an
incoming tertiary radical, that is, with no positive bond-energy
balance. Cyclization of 5d thus delivered sultine 6d, which is a
component of catꢀs urine (Table 3, entries 7 and 8).[39]
Interestingly, sultine-based natural products are not abun-
dant. Yet, both 6d and 6e have olfactory or flavor properties,
Keywords: cyclization · radical reactions · sulfinamides ·
.
sulfinates · sulfur heterocycles
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modifications of the former. For example, cyclization of
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Angew. Chem. Int. Ed. 2006, 45, 633 –637