Tetrahedron Letters,Vo1.30,No.23,pp Printed in Great Britain
0040-4039/89
3037-3040,1989
Maxwell
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ACONVEN~INSITDPROCEDURg FOREFFRCTINGIKPEB-AND
IINImmLRm
DIRE+AIDER REACTICMUS OF I-SULFONYL II¶INRS Joseph Department
Sisko
and Steven
of Chemistry,
University.
University
M. WeinrebX
The Pennsylvania Park.
State
Pennsylvania
16802
Treatment of an aldehyde and a 1,3-diene with N-sulfinyl-p-toluenesulfonamide/boron S-q: trifluoride etherate leads to products of an imino Diels-Alder reaction via an N-sulfonyl imine produced in situ. Since powerful
its inception
nearly
tool for construction
of the methodology
have been widely
in this area is the procedure of inmnonium salts under for effecting A number converted
five decades
utilized
cycloadditions
to the corresponding
3
in alkaloid
inter-
synthesis.
reaction
has become
a
and intramolecular
versions
A recent
advance
important
reaction et al., for in situ generation and Diels-Alder 2 We now describe a new one-pot method Mannich-like conditions.
of years ago Kresze
presence of a Lewis acid.
Both
of Grieco,
aqueous
Diels-Alder
ago, the imino Diels-Alder
of tetrahydropyridines.l
of N-sulfonyl
and co-workers
N-tosyl
We recently
imines
reported
imine using
derived
from a variety
that non-enolizable
N-sulfinyl-p-toluenesulfonamide
used the Kresze
reaction
of aldehydes.
aldehydes
to generate
could
be
in the
N-tosyl
imines
from
several
enolizable aldehydes which underwent subsequent intramolecular electrophilic cyclizations 4 We have now found that these in situ produced N-sulfonyl imines can be with olefins. efficiently Thus, followed
trapped treatment
by 1,3-dienes
by 2.3-dimethyl
butadiene
TsNSO BFJ-Et20/hAgS0.,
with N-sulfinyl-p-toluenesulfonamide
gives Diels-Alder
adduct
3 in good yield
and BP3 etherate (IQ 1).
It was also
O-so
EtCHO PhMe/CH&I,
in a [4+2]-cycloaddition.
of propionaldehyde
Et
A
I&
=/!:I
&ID&
Kq
-30% 1
2
3037
3
1)
3038
discovered anhydrous
that yields magnesium
are effective an initial intermediate complexed
is suspended
are slightly
of Die&-Alder
below.
Cycloadditions
stereoselectivity is that
be noted
compounds
derived
Moreover,
these
temperatures
than
cis-fused
structure
cases
shown
if
(4 A> also
presumably
involves
acid
aldehydes
which
aldehydes
the general
and
procedure
to be fully regioselective.
A useful
feature
sensitive
of the
enolieable
of N-sulfonyl
such as chloral
imines,
these
cycloadditions was obtained
these reactions
in the Scheme.
In this case,
Thus,
of adduct
such as 5 are potentially
aldehydes.
involve and glyoxylate. 3,5
generally
imines
require
higher
useful
intramolecularly
as shown
here which was tentatively
by the example assigned
the
experiments.
with other N-sulfinyl sulfonamide
4 with
EtCHO
SESNSO
6-10).
of relatively
product
based upon NOESY
Scheme
were found
of [4+2]-cycloadditions
the neutral
using
in our procedure.
to effect
treatment
(cf entries
non-enolizable
stereoisomeric
One can also perform
Me+
sieves
formation
of different
conducted
dienes
with a variety
all utilize
is necessary
A single
shown
was observed
from simple
in Eq 2.
Compounds
improved
Molecular
Imine
a number
were
with unsymmetrical
that existing
reactions
using
The reactions
it is successful
It is also possible
conditions.
mixture.
lower than with HgSO4,
cycloadditions
in the Table.
are shown
methodology
series
in the reaction
are substantially
salt 2.
Only modest
It should
in the reaction
!2+21-cycloaddition of the N-sulfinyl compound with the aldehyde affording an 3 such as I. The reactive species in the cycloaddition may in fact be a Lewis
The results
described
sulfate
but yields
immonium
1,3-dienes
and reproducibility
cleavage
fluorideb
in synthesis Me
afforded
sulfonamides
such as the SES 697
can be effected the bicyclic
of indolizidine
under mild 8 5.
lactam 9 alkaloids.
tfSES
I
BF3-Et,0 Me
MgSO4 PhMelCH,CI,
Me
-3oOc (SES= MeJSiCH2CH2S02-)
We are currently
56%
Me
MeO&(CH&CHO
exploring
extensions
and applications
of the methodology
described
here.
3039
TABLE. Diels-Alder Cycloadditions of in situ Generated N-Tosyl lminesa Entrv
Isolated Yield
ProductIs)
Diene
Aldehvde
Me 63%
Me(CH&CHO
1
(CHzkM~
Me Me
60%
[email protected]&CHO
2
Me Me 3
75%
PhCHOb Me
63%
EtCHO
4
Me
5
PhCHOb
60%
6
EtCHO
61%
7
EtCHO
8
EtCHO
73%
9
Me(CH&.CH0
74%
68%
(1.5:1)
IO
EtCHO
fJ-jEt
Me a see General b reaction
Experimental
conducted
’ stereochemistry
Procedure by ‘H NMR
Me
NOEDS
+yEt
Me (1:l)
at 0°C
established
+
44%
3040
General
Experisental
was added
Procedure.
200 mg of MgS04
toluenesulfonamide added
stirred
(0.3 mmol.
extracted
After
The 1,3-diene
The reaction
product
yields
was diluted
Acknowledgment. support.
with
We are grateful
For reviews
2.
see:
Weinreb,
to the National for obtaining
1987.
(c)
S.M.
Act. Chem. Res.
Larsen,
Albrecht,
4.
Melnick,
5.
Krow,
P.A.
NOESY
1965, 98,
M.J.;
G.; Rodebaugh,
R.; Marakowski,
Weinreb,
7.
The N-sulfinyl
Direct with
gel.
for financial
for NOEDS
spectra.
and Notes
R.R.
S.
Tetrahedron
1982, 38, 3087.
in Organic
Synthesis,"
Adv. Heterocvcl.
P.A.; Parker,
Pobare, B.
W.F.
Chem.
1768.
D.T.
(b)
Boger,
Academic
Press,
1987, 3,
Grieco,
245.
(d)
Lett.
1964, 97, 483.
Ber.
S.M.
Tetrahedron
P.A.; Larsen,
J. Org. Chem.
Tetrahedron
Chem.
J.; Ramey.
S.D.
1988, 53, 3325,
1986, 27,
Albrecht,
1975.
R.; Kresze, G.
see:
1988, 29, 3891.
Tetrahedron 1717.
1974, 30. 2977.
Tetrahedron aldehydes
K.C.
Lett.
1975, 1,
Tetrahedron
Lessen,
Krow, G.R.;
T.A.; Demers,
was prepared of:
of compounds generally
J.P.
Lett.
Krow,
1973, 1899.
G.R.;
Pyun, C.:
For cycloadditions Henz, K.J.;
Tetrahedron
from Me3SiCH2CH2S02NH2
Kim, Y.H.;
Shin, J.M.
like 5 via Die&z-Alder
does not work well:
in "Alkal'oids:
New York;
T.: Singer,
(Received
dried
TLC on silica
with N-acyl
Szczepanski,
S.W.
using
Tetrahedron reactions
Edwards,
0.E.;
Lett.
1986, 21, 2099.
the N-sulfinyl
1985, 3,
Lett.
3821.
of 1,2-dehydropyrrolidin-2-one Greaves,
A.M.;
Sy, W.-W.
1988, 66, 1163.
R.B.
John Wiley,
J.
D.M.;
procedure
formation
and
1888.
compound
1,3-dienes
Herbert,
W.N.
from enolizable
S.M.; Demko,
Can J. Chem.
10. Hori,
Speckamp,
1985, 0,
bis-imidazole
S.D.;
R.; Marakowski,
Rodebaugh,
6.
Grieco,
A.J.; Weinreb,
W.A.;
J. Org. Chem.
for 3
1985, 18, 16.
G.; Mlakar,
Freyer,
derived
solution
was
1431.
Zunnebeld,
imines
solution
was stirred
20 mL of H20,
(CA-34303)
and Dr. A. Freyer
J. Am. Chem. Sot. 1985, 107,
P.A.; Larsen,
R.; Kresze,
NaHC03 with
by preparative
Institute
Methodology
T.; Hibino,
1986, 51, 3553.
Grieco,
Chem. Ber.
9.
Kametani,
S.D.; Grieco,
was purified
Cancer
S.M.; Staib,
Diels-Alder
Orlando,
3658.
8.
Weinreb,
Weinreb.
J. Org. Chem.
3.
(a)
S.M. "Hetero
layer was washed
mixture
in the Table.
We thank Dr. A. Benesi
D.L.;
cap
N-Sulfinyl-p-
and the resulting
10 mL of saturated
The product
References
1.
by syringe
The organic
in vacua.
are shown
with a syringe
of argon.
(0.2 nm101) was added and the reaction
mixture
and concentrated
an atmosphere
fitted
in 2 mL of dry CH Cl and this solution was 2 2 the mixture to -30°C, the aldehyde (0.5 mmol) and
cooling
with 40 mL of ethyl acetate.
over MgS04 Isolated
flask.
under
25 mL flask
was dissolved
0.037 mL) were added sequentially
for 5 min.
h at -3O'C.
2-necked
and 3 mL of dry toluene
(0.3 xunol, 65 mg)l'
to the reaction
BP3eEt20
To an oven-dried,
in
USA
Chemical
S.P.; Sharpless, 22
and Biological
Perspectives";
Pelletier,
1985; vol. 3, p. 241.
March
K.B.
1989)
J. Org. Chem.
1978, 42, 1456.
S.W.,
Ed.;