its derivatives should result in scalemic R-sulfamidated
products. Thus, the proline-catalyzed aziridination of 2-phe-
nylpropionaldehyde with chloramine-T and PTAB was
carried out using standard conditions. Unfortunately, no level
of stereoselectivity could be observed, indicating the forma-
tion of enolates rather than enamines, and therefore no control
over the side of attack. Other proline derivatives were less
efficiant in terms of yields. Again, trisubstituted aldehydes
were found to be not reactive under these conditions.
A screening of different protic and aprotic solvents
revealed acetonitril8 to provide the best results in terms of
yield and reaction time, but in all cases only racemic products
were obtained. In most apolar solvents such as ether or THF,
only traces of the desired products could be found, together
with an increasing amount of toluenesulfonamide. This was
obviously due to the poor solubility of the catalysts L-proline
and PTAB.
The catalyst loading of L-proline could be lowered down
to 2 mol % without significant loss of conversion and yield,
respectively. Surprisingly, absence of the brominating agent
PTAB did not influence the formation of the product what-
soever, but identical yield and reaction time were observed.
Therefore the following set of reaction conditions was
established for further experimentation: addition of 1 equiv
of the aldehyde to a solution of 2 mol % of L-proline and a
slight excess of chloramine-T in acetonitrile until GC or TLC
indicated complete consumption of the aldehyde. This was
followed by subsequent isolation of the product by removal
of the solvent, and flash chromatography of the residue.
The effect of temperature was examined in acetonitrile
with L-proline as the catalyst. While no reaction had occurred
after 4 days at 0 °C, an acceleration could be observed at
elevated temperature. At 70 °C, the reaction time was
reduced to 5 h with significantly better yield (85%) compared
to room-temperature yields. This influence was further tested
by employing microwave conditions which benefit from
faster heating rates (Table 1). Variation of temperature,
maximum power, and reaction time led to the highest yield
of 90%, which was isolated after 30 min at 60 °C and 200
W. To further evaluate the effect of microwave irridation
and to determine its real impact on the reaction conditions,
comparative studies were performed using conventional
heating. As seen before, higher temperatures resulted in faster
reaction rates, with an optimum conversion at 60 °C. The
only noticeable difference observed to the microwave experi-
ments was the required reaction time, which had to be
extened to achieve comparable conversions and yields. Thus,
the observed rate enhancement is obviously a result of the
very fast heating rates when irridated in a microwave field
and most likely not attributed to a specific microwave effect.9
Once the optimum reaction conditions had been estab-
lished, the scope and limitation of this catalytic sulfamidation,
with respect to the substrates, were tested. Different para
substituted 2-phenylpropionaldehydes 1a-i were used to
Scheme 2. R-Sulfamidation of 2-Phenylpropionaldehyde 1a
with Chloramine-T under Pyrrolidine Catalysis
byproduct that was found turned out to be toluenesulfon-
amide, which was formed from chloramine-T in very low
quantity (less than 5%). This observation seemed to confirm
our assumption of an in-situ generated enamine whose double
bond is most likely halogenated by tribromide. The formed
bromonium species will then be attacked by the nucleophilic
chloramine-T to yield the aziridine intermediate. This theory
is further supported by the observation that aldehydes without
R-protons such as pivaldehyde do not react at all under these
conditions, thus verifying the required formation of an
enamine intermediate.
On the basis of this pathway for olefins proposed by Sharp-
less, substitution of the achiral pyrrolidine with L-proline or
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