Organic Letters
Letter
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a
Scheme 1. Pd-Catalyzed SO2-Insertion Strategies
Scheme 2. Scope of Sulfonylated Oxindoles
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Selected examples of Pd-catalyzed sulfonylation reaction strategies
using DABSO as the SO2 surrogate, and proposed work.
aryl halidesa useful methodology which avoids the isolation
of the sulfinate intermediate.5c These reports highlight the
potential to readily incorporate SO2 using DABSO in
conjunction with palladium catalysis; however, its application
toward more complex frameworks has yet to be realized.4,5
Therefore, we sought out to employ DABSO in a Pd-catalyzed
domino-Heck process with the aim of developing a general
method to access sulfur-containing hetero- and carbocycles.
Our optimal conditions employ aryl iodide 1a and DABSO
and resemble conditions similar to those previously reported.8a
By employing Pd(OAc)2 (5 mol %), PPh3 (10 mol %), TEA (2
equiv), and DABSO (1.5 equiv) in DMF at 80 °C for 16 h (see
generated. Subsequent addition of tert-butyl bromoacetate (3
equiv) at room temperature gave the desired sulfonylated
oxindole product 2a in 74% yield (Scheme 2).
After establishing the optimal conditions, we explored the
scope of the oxindole products that could be produced
(Scheme 2). Substrates incorporating substituents in the para-
position relative to the iodide had a minimal impact of the
yield. Product 2b bearing a p-methyl was isolated in 73% yield
along with p-methoxy and chloro products 2c and 2d in 65%
and 80% yield, respectively. Moving the chloro substituent to
the meta-position produced product 2e in 71% yield. Tethering
a phenyl ring to the alkene in the place of a methyl group was
tolerated and gave product 2f in 76% yield. These phenyl
derivatives could tolerate various substituents such as the
methylenedioxy backbone found in 2g (67% yield) and
substituents on the tethered phenyl ring such as a p-CF3
group found in product 2i (71% yield). An oxindole, bearing a
benzyl group on the nitrogen atom, was successfully
synthesized giving product 2h in 70% yield. The benzyl
derivatives were also able to tolerate fluoro and ester
substituents in the meta-position, furnishing 2j and 2k in
69% and 70% yield, respectively. An example of m-nitrobenzyl
bromide and m-iodobenzyl bromide acting as the alkyl halide
electrophile gave product 2l and 2m both in 66% yield. While
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Reaction scope of selected accessible oxindoles (0.2 mmol scale). All
reported yields are after isolation.
unactivated alkyl bromides gave lower yields at room
temperature, as seen with product 2n (32%), this example
highlights the variety of functionalized dialkylated sulfones
accessible.
Other hetero- and carbocyclic products could be accessed
using this methodology including sulfonylated dihydrobenzo-
furans, indanes, isochromans, and tetrahydronaphthalenes
(Scheme 3). The dihydrobenzofuran 4a was isolated in 75%
yield. At 1 mmol, 4a was isolated in a somewhat reduced yield
of 68%. Introducing a m-chloro substituent lowered the yield
slightly to 65% of 4b. Similarly, the yield of 4c was
considerably lower (41%) when a methoxy group was present
ortho with respect to the tethered alkene substituent.
Isochroman 4d and Indane 4e were successfully generated in
the reaction, being isolated in 77% and 75%, respectively.
These results led us to then attempt to synthesize a six-
membered carbocyclic product 4f, which was isolated in 67%
yield.
The majority of previous reports of cyclization/SO2
incorporation are limited to the generation of sulfones. By
exploiting the sulfinate lynchpin, we aimed to explore the
versatility of this methodology. We prepared sulfonamides in a
one-pot, two-step fashion following procedures reported by
Fier and Maloney (Scheme 4).16 Following generation of the
sulfinate, introduction of piperidine (1.5 equiv) and I2 (1
equiv) at room temperature led to the formation of
dihydrobenzofuran sulfonamide 5a and oxindole-based sulfo-
namide 5b which were isolated in 52% and 59% yield,
2798
Org. Lett. 2021, 23, 2797−2801
Bajohr, Jonathan
