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Carbon-nitrogen bond formation via acyl-nitroso compounds. Intramolecular ene processes.
Tetrahedron Lptters No. 14, ap 1185 - 1186. @Perqmon Freqs Ltd. 1979. Printed in Great Britain.
.
CARBON-NITROGEN
BOND FORMATION INTRAMOLECULAR
Department Acyl-mtroso which
operations
compounds,
possible
to alkaloid
adduct
descnbed,ly2
of lithium
Similarly,
substrate
?j in good yield.
dehyde were readily dimethylsilyl
ethers.
due to their extreme intermediates reactions
converted
The adducts
prepared
essentially prepared I.
The
exclusively
of acyl-nitroso
enolate
enolate
compounds
for
intramolecu-
upon treatment was
products
by condensation
found
of such
SUBSTRATES
in moderate
to afford ene
with methacrolein
in Table
with 1 2
to condense
of 1,2 addition
to their corresponding
for study are summarized
w(a)*b
The
for a number of synthetic
with 1-bromo-3-methyl-2-butene
quantitatively,
ENE REACTION
reactivity.'
species
and g,lO-dimethylanthracene,prepared
to its lithium
alkylated
reactive
is known about the ene reactivity
at -78' C.
to afford
84112
we have been led to investigate
Little
nitrosocarbonylmethane
smoothly
TABLE Substrate
total synthesls,2
in THF-HMPA
Substrates
isolated
RCDNO, are exceptionally
them attractive
compounds
aldehydes
converted,
formula
in C-N bond forming
is readily
the enolate
or
makes
between
dllsopropylamlde
readily with a,8 unsaturated yields.
observed
of acyl-nltroso
The Diels-Alder as previously
the general
of our interest
applications
lar ene reactions 1 compounds
eq
having
of these compounds
Because
COMPOUNDS
Gary E Keck,* Robert Webb of Chemistry, University of Utah, Salt Lake City, Utah
have never been directly
high reactivity
J/IJ ACYL-NITROSO
ENE PROCESSES
and crotonaltert-butyl
I.3
AND PRODUCTS Ene Product
65%
Yielda
100%
50%
100% /OH
0 3 N0 -c
74%
0
100%
/ *
\‘/
(a) All yields reported are isolated yields, (b) for those substrates sllyation, the reported yield is an overall yield for the two steps
1185
prepared
via condensatlon-
1186
No. 14
Using substrates heating
1-3 in Table I, the intramolecular ene process was effected simply by -.?" solutions at reflux for 3-5 hr , rnth tic monltonng of reactant consumption
benzene
Thus,
retro-Duels-Alder
which
then undergoes
fragmentation
serves
the intramolecular
to liberate
ene reaction 0
the highly reactive
acyl-nltroso
moiety,
with facility.
A 3-
-6 +9,10-DMA
Isolation
of products
ducts shown in Table
was accomplished
the rather polar cyclic
hydroxamic
veals that the intramolecular 4 cesses The cyclic by exposure
hydroxamic
to acetic
in the acetates for example,
by chromatography
I in the indicated
yields
acids and is thus easily
ene reactions
acids obtained
anhydrlde-pyndine
then affords
6 was converted
over Florisll,
Dlmethylanthracene
by this process for 10 mln
the corresponding
r,
recycled
WOH
The mild condltlons employment
ln natural
lactams
Reductive
in our laboratories Acknowledgement.
Et 6 H
Using this
procedure,
Z +--
4
described Further
synthesis
Institute
yield
of the N-O bond
NH
2);; /$9)
above make them particularly studies
to natural
to delineate
products
attractive
for
the scope and generality
total synthesis,
are in progress
in due course.
of this research
Cancer
I re-
0
as well as extension
Support
of Table
from
yield
11Ac20-Pyr
and ~111 be reported
Fund, and the National
separated
in quantitative
cleavage5
in high yields.
7 ln 98% isolated
of the processes
products
of the above reactions,
Inspection
are 0-acetylated
0
6
the ene pro-
of both types I (1 and 3) and II (2) are facile pro-
at23'
to lactam
affording
1s very easily
by the Research
(through
Corporation,
the Petroleum
Research
NC1 Grant #l ROl CA 24166) is gratefully
acknowledged REFERENCES 1
For a recent (1978)
survey of acyl-nltroso
chemistry,
note 6. W
Kirby, Chem
Sot
Reviews,
2
G
3.
All new compounds geneous samples
4.
For an excellent recent review and classlflcation of intramolecular ene reactions Oppolzer, Ang Chem Int Ed. Engl , 17, 486 (1978) __ G. E Keck, S. Fleming, D Nlckell, and P Welder, Syn Conan , in press
5
E. Keck, Tetrahedron
Lett
6, 1
, 4767 (1978).
reported gave satisfactory spectral data using chromatographlcally Full experimental details will be given in our full paper
(Received In USA 2 December 1978)
home-
note W
.
CARBON-NITROGEN
BOND FORMATION INTRAMOLECULAR
Department Acyl-mtroso which
operations
compounds,
possible
to alkaloid
adduct
descnbed,ly2
of lithium
Similarly,
substrate
?j in good yield.
dehyde were readily dimethylsilyl
ethers.
due to their extreme intermediates reactions
converted
The adducts
prepared
essentially prepared I.
The
exclusively
of acyl-nitroso
enolate
enolate
compounds
for
intramolecu-
upon treatment was
products
by condensation
found
of such
SUBSTRATES
in moderate
to afford ene
with methacrolein
in Table
with 1 2
to condense
of 1,2 addition
to their corresponding
for study are summarized
w(a)*b
The
for a number of synthetic
with 1-bromo-3-methyl-2-butene
quantitatively,
ENE REACTION
reactivity.'
species
and g,lO-dimethylanthracene,prepared
to its lithium
alkylated
reactive
is known about the ene reactivity
at -78' C.
to afford
84112
we have been led to investigate
Little
nitrosocarbonylmethane
smoothly
TABLE Substrate
total synthesls,2
in THF-HMPA
Substrates
isolated
RCDNO, are exceptionally
them attractive
compounds
aldehydes
converted,
formula
in C-N bond forming
is readily
the enolate
or
makes
between
dllsopropylamlde
readily with a,8 unsaturated yields.
observed
of acyl-nltroso
The Diels-Alder as previously
the general
of our interest
applications
lar ene reactions 1 compounds
eq
having
of these compounds
Because
COMPOUNDS
Gary E Keck,* Robert Webb of Chemistry, University of Utah, Salt Lake City, Utah
have never been directly
high reactivity
J/IJ ACYL-NITROSO
ENE PROCESSES
and crotonaltert-butyl
I.3
AND PRODUCTS Ene Product
65%
Yielda
100%
50%
100% /OH
0 3 N0 -c
74%
0
100%
/ *
\‘/
(a) All yields reported are isolated yields, (b) for those substrates sllyation, the reported yield is an overall yield for the two steps
1185
prepared
via condensatlon-
1186
No. 14
Using substrates heating
1-3 in Table I, the intramolecular ene process was effected simply by -.?" solutions at reflux for 3-5 hr , rnth tic monltonng of reactant consumption
benzene
Thus,
retro-Duels-Alder
which
then undergoes
fragmentation
serves
the intramolecular
to liberate
ene reaction 0
the highly reactive
acyl-nltroso
moiety,
with facility.
A 3-
-6 +9,10-DMA
Isolation
of products
ducts shown in Table
was accomplished
the rather polar cyclic
hydroxamic
veals that the intramolecular 4 cesses The cyclic by exposure
hydroxamic
to acetic
in the acetates for example,
by chromatography
I in the indicated
yields
acids and is thus easily
ene reactions
acids obtained
anhydrlde-pyndine
then affords
6 was converted
over Florisll,
Dlmethylanthracene
by this process for 10 mln
the corresponding
r,
recycled
WOH
The mild condltlons employment
ln natural
lactams
Reductive
in our laboratories Acknowledgement.
Et 6 H
Using this
procedure,
Z +--
4
described Further
synthesis
Institute
yield
of the N-O bond
NH
2);; /$9)
above make them particularly studies
to natural
to delineate
products
attractive
for
the scope and generality
total synthesis,
are in progress
in due course.
of this research
Cancer
I re-
0
as well as extension
Support
of Table
from
yield
11Ac20-Pyr
and ~111 be reported
Fund, and the National
separated
in quantitative
cleavage5
in high yields.
7 ln 98% isolated
of the processes
products
of the above reactions,
Inspection
are 0-acetylated
0
6
the ene pro-
of both types I (1 and 3) and II (2) are facile pro-
at23'
to lactam
affording
1s very easily
by the Research
(through
Corporation,
the Petroleum
Research
NC1 Grant #l ROl CA 24166) is gratefully
acknowledged REFERENCES 1
For a recent (1978)
survey of acyl-nltroso
chemistry,
note 6. W
Kirby, Chem
Sot
Reviews,
2
G
3.
All new compounds geneous samples
4.
For an excellent recent review and classlflcation of intramolecular ene reactions Oppolzer, Ang Chem Int Ed. Engl , 17, 486 (1978) __ G. E Keck, S. Fleming, D Nlckell, and P Welder, Syn Conan , in press
5
E. Keck, Tetrahedron
Lett
6, 1
, 4767 (1978).
reported gave satisfactory spectral data using chromatographlcally Full experimental details will be given in our full paper
(Received In USA 2 December 1978)
home-
note W