Organic Letters
Letter
Scheme 2. Reactivity of Meldrum’s Acid Derivatives,
8d bearing an electron-donating ether group on the arene,
which gave 13ad in only 28%. The moderate yield of 13af
(48%) is a result of the water sensitivity of 8f, which rapidly
hydrolyzes. On a 4 mmol scale, 13aa was obtained in 90%
yield.
Assumed Compounds 10aa and 11aa and Obtained Product
16
1
3aa
Next, the sulfur component was varied, and several other N-
cyanosulfoximines were applied in reactions with Meldrum’s
acid derivative 8a (Scheme 3). Again, the yields of the
corresponding products 13ba−ia spanned a wide range (from
1
5% to 87%). Among the S-alkyl S-aryl derivatives, S-
cyclopropyl S-phenyl sulfoximine 3b performed best providing
3ba in 87% yield. For unknown reasons, the presence of a
para substituent on the arene reduced the product yields
1
(
13ca−ga). Distinct electronic effects were not identified. An
interesting observation was made in the reaction of 8a with p-
formyl-substituted sulfoximine 3g. In this case, we expected the
formation of 13ga, but instead compound 14 was obtained
(
13% yield). Presumably, 14 stemmed from 13ga, which had
undergone a subsequent aldol reaction with in situ formed
acetone resulting from the degradation of Meldrum’s acid
derivative 8a. NMR spectroscopy suggested an exclusive
formation of the Z isomer of 14, which contrasted observations
by Bhat and co-workers, who found high E selectivities in
related organocatalytic reactions providing α,β-unsaturated
from the reaction of 3a with 8a was performed (Scheme 2).
Again, we were caught by surprise because none of the so far
considered structures were correct. Instead of 10aa or 11aa, an
isomer of 11aa (product 13aa) representing a sulfoximine with
an N-bound 5-carbonyl-1,3-oxazine-2,4-dione group was
found.
18
ketones. While the use of S,S-diphenyl sulfoximine 3h led to
1
1
3ha in 83% yield, S,S-dialkyl-substituted substrate 3i afforded
3ia in only 30% yield.
Scheme 4 shows a tentative multistep reaction sequence
converting N-cyanosulfoximines 3 and Meldrum’s acid
Varying the reaction parameters revealed that 13aa could be
obtained in 99% yield when a 1:4 mixture of 3a and 8a in
17
toluene was kept for 2 h at 120 °C. Under these conditions,
other Meldrum’s acid derivatives reacted with 3a analogously
providing the corresponding products 13ab−af in yields
ranging from 28% to 86% yield (Scheme 3). In this series,
the best results were obtained with substrates 8a and 8b having
3
as R a methyl or a benzyl group, respectively. Lower yields
were observed with Meldrum’s acid derivatives 8c−f having
aryl substituents at that position. This was particularly true for
Scheme 3. Substrate Scope
derivatives 8 to the observed products 13. Because none of
the depicted intermediates A−G could be isolated or detected,
the proposed transformation has to be taken with great care.
The process is initiated by elimination of acetone from 8
providing zwitterion A. (Note that A could loose CO leading
2
to acylketene 9. Then, however, CO would have to re-enter at
2
a later stage because it is part of the product.) Regioselective
addition of A on N-cyanosulfoximine 3 yields intermediate B.
Initially, we hypothesized that the formation of the N-acyl
group of 13 involved the addition of water to B (or B′) to give
B
Org. Lett. XXXX, XXX, XXX−XXX