Organic Letters
Letter
Also, we have recently reported an unusual reaction of alkyne-
containing chlorosulfate derivatives to get sultones (Scheme
1b).9 This thermal reaction proceeds through an initial ring-
expansion process that renders an ionic pair II, which after an
elimination reaction and the subsequent addition of the in-situ-
formed chlorosulfonic acid forms the final sultone derivatives.
Taking into account all of this precedent work, we conceived a
new method to get spirocarbocycles from simple chlorosulfate
derivatives based on a cascade ring-expansion/cationic cycliza-
tion/halide-trapping process (Scheme 1c). More precisely, we
considered that chlorosulfate derivatives 1, similar to those
shown in Scheme 1b but containing a longer chain connecting
the alkyne and the quaternary carbon, should evolve under
thermal conditions to get cationic species 2 through a ring-
expansion reaction. Considering our work shown in Scheme 1a,
this cation could be trapped by the alkyne to form alkenyl cation
3, which, in the presence of a halogen source, should render
spirocarbocycles 4. Details of the development of this cascade
process and other related reactions aimed to the synthesis of
spirocarbocycles are shown herein.
dichloroethane, we observed the formation of complex mixtures
of products where the desired [5.6] spirocarbocycle 4a could not
be identified. All of these experiments showed that the proposed
strategy to get spirocarbocycles was viable but only when
chlorosulfate derivatives were used as starting materials.10 The
absence of reactivity, under our reaction conditions, of the
mesylate and tosylate derivatives could be associated with their
poorer leaving group ability (OMs < OTs < OSO2Cl < OTf).
On the contrary, the triflate derivative seemed to be too
reactive.11
At this point, it should be noted that most of the known
reactivity of chlorosulfates is limited to formal substitutions of
the chlorine atom by nucleophiles.12 Consequently, the
previously described reaction supposes a new application of
chlorosulfate derivatives in organic synthesis. It should also be
noted that the new reaction described here does not require any
reagent or additive and is just a thermal process. This makes this
reaction different from our previous work on the synthesis of
alkenyl halides where an acid was required to promote the
reaction.7a
In our initial experiment, chlorosulfate derivative 1a was used
as a model substrate to explore the viability of the proposed
strategy (Table 1, entry 1). Thus, taking into account our
Next, we explored the scope of the reaction on different
substrates (Scheme 2). To get spirocarbocycles substituted with
Scheme 2. Synthesis of Alkenyl-Halide-Containing
Spirocarbocycles 4
Table 1. Initial Experiments
a
entry
starting mat.
X
yield (%)
1
2
3
4
1a
5
6
7
8
ClSO2
92
b
MeSO2
4-MeC6H4SO2
CF3SO2
H
b
d
d
c
5
a
b
c
Based on 1a and 5−8. Starting material recovered. Reaction
d
performed in the presence of 1 equiv of HBF4·Et2O. Complex
mixture of unidentified products.
previous research,7,9 we simply heated this compound to 50 °C
in 1,2-dichloroethane as the solvent and the source of chloride.
Gratifyingly, we observed the clean formation of the desired
[5.6] spirocarbocycle 4a in very high yield (92%). Considering
that in this reaction the chlorosulfate group formally acted as a
leaving group, we thought that other leaving groups could also
be appropriate in this transformation. Thus, to determine if this
new reaction was specific to chlorosulfates or if it could be
performed with related reagents, we did some additional
experiments. We tried the reaction with starting materials such
as mesylate (5), tosylate (6), and triflate (7) derivatives (Table
1, entries 2−4). Despite containing excellent leaving groups, low
reactivity and the formation of complex mixtures was observed
when they were reacted under identical conditions to those
previously applied for chlorosulfate 1a. We also considered the
possibility of getting our desired product 4a from alcohol 8
(Table 1, entry 5). From this starting material, we thought that
the formation of the initial cation II (see Scheme 1b) could be
promoted by an acid. However, when this alcohol 8 was reacted
with one equivalent of tetrafluoroboric acid (HBF4) in 1,2-
a
b
c
Solvent = 1,2-dichloroethane. Solvent = dibromomethane. Solvent
= iodomethane; reactions performed in a sealed tube.
different halogen atoms, the reactions were performed with
different halogenated solvents (1,2-dichloroethane, dibromo-
methane, or methyl iodide). Thus considering that these
solvents also served as a source of halide,7a,13 several spirocyclic
compounds containing an alkenyl chloride, bromide, or iodide
were obtained in high yield. As shown, [5.5], [5.6], and [5.7]
spirocarbocycles were easily obtained. However, regarding the
new carbocycle containing the alkenyl halide moiety, we were
not able to extend the method to the synthesis of other cycles
different from a six-membered ring.7
Interestingly, this method could be adapted to get spirocyclic
compounds containing a ketone functionality (Scheme 3). Thus
when the solvent of the reaction was changed from a
halogenated one to wet hexafluoro-2-propanol,7b ketones 9
were isolated in high yields. These products are supposed to be
B
Org. Lett. XXXX, XXX, XXX−XXX
Cala, Lara
