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Enantioselection in the birch reduction-alkylation of a chiral benzoic acid derivative
Tetrahedron Letters,Vol.25,No.41,pp Printed in Great Britain
ENANTIOSELECTION
Department
0040-4039/84 $3.00 + .OO 01984 Pergamon Press Ltd.
IN THE BIRCH REOUCTION-ALKYLATION
OF A CHIRAL Arthur
4591-4594,1984
BENZOIC
G. Schultz*
ACIO DERIVATIVE
and Padmanabhan
Sundararaman
of Chemistry, Rensselaer Polytechnic Troy, New York 12181
Institute
Preparationand diastereoselective Birch reduction-alkylation Summary: 3 is described; conversion of 3 to % enantiomerically pure -ll confirms selection in the alkylation step. The Birch
reduction-alkylation
cyclohexadienes to natural
is one of the most useful
product
preparation
synthesis
and illustrate
We have reported of diastereoisomeric The absence the chira1
auxiliary
reduction-alkylation
cyclohexadienes
about
movement
the ester within
of a chira1
method
for
by Birch
re-
benzoic
acid derivative
of tricyclo[4.3.1.03s7]decenone
ester of o-methoxybenzoic
C-O bond.
in the alkylation
3 for exploratory
of o-hydroxybenzoic (1 equiv),
acid gave a 1:l mixture
on Birch reduction-alkylation
been
acid
in part,
We expected
a benzo-fused
derived
hexylcarbodiimide
a versatile
applications
In this note, we report the first
to the synthesis
must be due, at least
had already
Reaction
Severa1
pure form.
2-methoxybenzamides heterocycle
synthesis.
and we have developed
acid derivatives.l
that the d-menthol
of stereocontrol
in organic
to give 6,6-disubstituted-1,4-
carboxamido)-2,4-cyclohexadien-l-ones
of the method
of stereoselection
to conformational measure
Birch
an application
-11 in 'L enantiomerically
reactions
(and
of o-methoxybenzoic
for enantioselective
acid derivatives
have been recorded
of 6-alkyl-6-carboalkoxy
duction-alkylation method
of benzoic
of benzoxazepenone the -98:Z diastereo-
to the freedom
that
seven-membered
step.'
Birch
demonstrated;lb
with methyl
restraining
iodide.lb
of rotation the chira1
ring system might
reduction-alkylation
we, therefore,
of
center
provide
a
of tJ,fj-dialkyl-
selected
L-prolinol
studies. (i) with t+methylmorpholine
1-hydroxybenzotriazole
in THF at Oo gave amide 2 in Q quantitative
yield." 4591
(1 equiv), Cyclization
(2 equiv),
N,_-dicyclo-
and L-prolino13
(1 equiv)
of 2 was performed
in -80%
4592
overa11 zation to
yield
from -1 by use of the Mitsunobu
resulted
the enamide
in formation
of varying
reaction
amounts
(not shown) and intramolecular
conditions.5
of benzoxazinone phenol-olefin
Other methods 4, presumably
of cycli-
by elimination
addition.6
Me 4
&--- &-- ‘f-2 R !&,
-6
R = Me
2,
8a_,R
R = Me
b,R=H
d, R = Et
= Me
d, R = CH2CH2CH=CH2
c, R = CH2CH=CH2 d, R = CHrCHzCH=CH2
Benzoxazepenone
3 underwent
the presente
of tert-butano1
with
common
severa1
4-bromo-l-butene
alkylation
(Table
tively,
was found
entries
l-3).
(1 equiv). reagents; With methyl
to be independent
With alkylation
diastereoselectivity A small amount with methyl
1).
Birch-reduction
of y-alkylation
iodide.
This material
iodide,
to give -7a (a tetrasubstituted
from alkylation
iodide,
ethyl ratio
hindered
to be formed
vinylogous
A small amount
with allyl
bromide.
iodide,
step
than methyl
entries
treated
(K, Na, Li; iodide,
from enolate
the
rather
alkylation
diastereoisomer,
but
that y-alkylation
than y' to give a triof y-protonation,
and
respec-
4-6).
It is noteworthy
of the product
in
allyl bromide
(5a:6a) of 85:15, --
as a single
urethane)
solution
was subsequently
in the reduction
(>98:2;
has not as yet been determined.
(not shown).
enolate
the product used
in NH,-THF
amide
more sterically
appeared
occurred
was produced
methyl
metals
product -7a (-3%) was obtained
configuration
acrylamide
s,
was outstanding
relative
substituted
The resulting
of the metal
reagents
of alkylation
with alkali
0,
4594
9 Continuing
studies
in enantioselective of aldol
natural
condensations
and 3) the development optically
active
are directed product
at 1) the utilization syntheses,
2) an examination
of the chira1 amide enolate of protocols
cyclohexanes
of this chira1
derived
for the conversion
for use in organic
auxiliary
method
of the diastereoselectivity
from -3 and related
of benzoic
acids
enolates,
to a wide
range of
synthesis."
Acknowledgment. This work was supported by the National Institutes of Health (GM 26568). NMR spectra were recorded on a Varian XL-200 instrument purchased with funds provided, in part, by a National Science Foundation Department Instrumentation Grant. Mass spectra were obtained on a Hewlett-Packard 5987A GC-MS system purchased with funds provided by the National Science Foundation and Grant No. 1 510 RR01677 awarded by the National Institutes of HealthBRS Shared Instrumentation Program. Referentes
1. 2.
and Notes
Lett. 1983, 2, 1369. (b) Schultz, A. ia) Schultz, A. G.; Dittami, J. P. Tetrahedron . Dittami, J. P.; Lavleri, F. P.; Salowey, C.; Sundararaman, P.; Szymula, M. 8. J:‘Org Chem., in press and referentes cited therein. For a report of stereoselection in the alkylation of cyclic bis-lactim ethers derived from L-amino acids, see Schöllkopf, W.; Groth, U.; Westphalen, K. 0.; Deng, C. Synthesis
1981, 969.
3.
For the use of prolinol Fg8i. 2&$&!i?$
4. 65:
7. 8. 9. 30.
derivatives
as chira1 auxiliaries
see (a) Sonnet,
:~~bac~,,"t3Kali~~?s,'ran~~_~:;As6s:a~~css
P. E.; Heath,
J.C;assTetGrah;al;mn k-;t+
Dörr: rr DuPreez, N. P.; Eh;ig;'V.; Langer,'W.; Nüssler, C.; Oe;, H.-AT; Sihmidt: M. Helv. Chim. Acta 1977, 60, 301. (d) Enders, D.; Eichenauer, H. Angew. Chem. Int. Ed. Engl. 1979, 18, 397. (v Kolb, M.; Barth, J. Angew. Chem. Int. Ed. Engl. 1980, 0, 725. (g) Mukãiyama, T. Tetrahedron 1981, 2, 4111. 11 gave satisfactory combustion analyses. Compounds 2, 3, 4, sc, _, @, ¿&, &, S nthesis 1981, 1 and reierences cited therein. Mitsunobu, 0. was obtainedin 73% yield from the chloromethyl derivative of 1 +~ Benzoxazinone (mp 136-138"C, from treatment of 2 with SOC12-triethylamine in CHCIS; 74% yield) by reaction with K2C03 in acetone. Birch reduction-alkylation reaction conditions were similar to those described in detail in referente 1. Schultz, A. G.; Snead, T.; Lavieri, F. P. manuscript in preparation. Available from Aldrich Chemical Company. An analysis of stereochemical control in reactions of amide enolates derived from 2 together with complete experimental details will be presented in the ful1 paper resulting from this work.
(Received in USA 18 June 1984)
ENANTIOSELECTION
Department
0040-4039/84 $3.00 + .OO 01984 Pergamon Press Ltd.
IN THE BIRCH REOUCTION-ALKYLATION
OF A CHIRAL Arthur
4591-4594,1984
BENZOIC
G. Schultz*
ACIO DERIVATIVE
and Padmanabhan
Sundararaman
of Chemistry, Rensselaer Polytechnic Troy, New York 12181
Institute
Preparationand diastereoselective Birch reduction-alkylation Summary: 3 is described; conversion of 3 to % enantiomerically pure -ll confirms selection in the alkylation step. The Birch
reduction-alkylation
cyclohexadienes to natural
is one of the most useful
product
preparation
synthesis
and illustrate
We have reported of diastereoisomeric The absence the chira1
auxiliary
reduction-alkylation
cyclohexadienes
about
movement
the ester within
of a chira1
method
for
by Birch
re-
benzoic
acid derivative
of tricyclo[4.3.1.03s7]decenone
ester of o-methoxybenzoic
C-O bond.
in the alkylation
3 for exploratory
of o-hydroxybenzoic (1 equiv),
acid gave a 1:l mixture
on Birch reduction-alkylation
been
acid
in part,
We expected
a benzo-fused
derived
hexylcarbodiimide
a versatile
applications
In this note, we report the first
to the synthesis
must be due, at least
had already
Reaction
Severa1
pure form.
2-methoxybenzamides heterocycle
synthesis.
and we have developed
acid derivatives.l
that the d-menthol
of stereocontrol
in organic
to give 6,6-disubstituted-1,4-
carboxamido)-2,4-cyclohexadien-l-ones
of the method
of stereoselection
to conformational measure
Birch
an application
-11 in 'L enantiomerically
reactions
(and
of o-methoxybenzoic
for enantioselective
acid derivatives
have been recorded
of 6-alkyl-6-carboalkoxy
duction-alkylation method
of benzoic
of benzoxazepenone the -98:Z diastereo-
to the freedom
that
seven-membered
step.'
Birch
demonstrated;lb
with methyl
restraining
iodide.lb
of rotation the chira1
ring system might
reduction-alkylation
we, therefore,
of
center
provide
a
of tJ,fj-dialkyl-
selected
L-prolinol
studies. (i) with t+methylmorpholine
1-hydroxybenzotriazole
in THF at Oo gave amide 2 in Q quantitative
yield." 4591
(1 equiv), Cyclization
(2 equiv),
N,_-dicyclo-
and L-prolino13
(1 equiv)
of 2 was performed
in -80%
4592
overa11 zation to
yield
from -1 by use of the Mitsunobu
resulted
the enamide
in formation
of varying
reaction
amounts
(not shown) and intramolecular
conditions.5
of benzoxazinone phenol-olefin
Other methods 4, presumably
of cycli-
by elimination
addition.6
Me 4
&--- &-- ‘f-2 R !&,
-6
R = Me
2,
8a_,R
R = Me
b,R=H
d, R = Et
= Me
d, R = CH2CH2CH=CH2
c, R = CH2CH=CH2 d, R = CHrCHzCH=CH2
Benzoxazepenone
3 underwent
the presente
of tert-butano1
with
common
severa1
4-bromo-l-butene
alkylation
(Table
tively,
was found
entries
l-3).
(1 equiv). reagents; With methyl
to be independent
With alkylation
diastereoselectivity A small amount with methyl
1).
Birch-reduction
of y-alkylation
iodide.
This material
iodide,
to give -7a (a tetrasubstituted
from alkylation
iodide,
ethyl ratio
hindered
to be formed
vinylogous
A small amount
with allyl
bromide.
iodide,
step
than methyl
entries
treated
(K, Na, Li; iodide,
from enolate
the
rather
alkylation
diastereoisomer,
but
that y-alkylation
than y' to give a triof y-protonation,
and
respec-
4-6).
It is noteworthy
of the product
in
allyl bromide
(5a:6a) of 85:15, --
as a single
urethane)
solution
was subsequently
in the reduction
(>98:2;
has not as yet been determined.
(not shown).
enolate
the product used
in NH,-THF
amide
more sterically
appeared
occurred
was produced
methyl
metals
product -7a (-3%) was obtained
configuration
acrylamide
s,
was outstanding
relative
substituted
The resulting
of the metal
reagents
of alkylation
with alkali
0,
4594
9 Continuing
studies
in enantioselective of aldol
natural
condensations
and 3) the development optically
active
are directed product
at 1) the utilization syntheses,
2) an examination
of the chira1 amide enolate of protocols
cyclohexanes
of this chira1
derived
for the conversion
for use in organic
auxiliary
method
of the diastereoselectivity
from -3 and related
of benzoic
acids
enolates,
to a wide
range of
synthesis."
Acknowledgment. This work was supported by the National Institutes of Health (GM 26568). NMR spectra were recorded on a Varian XL-200 instrument purchased with funds provided, in part, by a National Science Foundation Department Instrumentation Grant. Mass spectra were obtained on a Hewlett-Packard 5987A GC-MS system purchased with funds provided by the National Science Foundation and Grant No. 1 510 RR01677 awarded by the National Institutes of HealthBRS Shared Instrumentation Program. Referentes
1. 2.
and Notes
Lett. 1983, 2, 1369. (b) Schultz, A. ia) Schultz, A. G.; Dittami, J. P. Tetrahedron . Dittami, J. P.; Lavleri, F. P.; Salowey, C.; Sundararaman, P.; Szymula, M. 8. J:‘Org Chem., in press and referentes cited therein. For a report of stereoselection in the alkylation of cyclic bis-lactim ethers derived from L-amino acids, see Schöllkopf, W.; Groth, U.; Westphalen, K. 0.; Deng, C. Synthesis
1981, 969.
3.
For the use of prolinol Fg8i. 2&$&!i?$
4. 65:
7. 8. 9. 30.
derivatives
as chira1 auxiliaries
see (a) Sonnet,
:~~bac~,,"t3Kali~~?s,'ran~~_~:;As6s:a~~css
P. E.; Heath,
J.C;assTetGrah;al;mn k-;t+
Dörr: rr DuPreez, N. P.; Eh;ig;'V.; Langer,'W.; Nüssler, C.; Oe;, H.-AT; Sihmidt: M. Helv. Chim. Acta 1977, 60, 301. (d) Enders, D.; Eichenauer, H. Angew. Chem. Int. Ed. Engl. 1979, 18, 397. (v Kolb, M.; Barth, J. Angew. Chem. Int. Ed. Engl. 1980, 0, 725. (g) Mukãiyama, T. Tetrahedron 1981, 2, 4111. 11 gave satisfactory combustion analyses. Compounds 2, 3, 4, sc, _, @, ¿&, &, S nthesis 1981, 1 and reierences cited therein. Mitsunobu, 0. was obtainedin 73% yield from the chloromethyl derivative of 1 +~ Benzoxazinone (mp 136-138"C, from treatment of 2 with SOC12-triethylamine in CHCIS; 74% yield) by reaction with K2C03 in acetone. Birch reduction-alkylation reaction conditions were similar to those described in detail in referente 1. Schultz, A. G.; Snead, T.; Lavieri, F. P. manuscript in preparation. Available from Aldrich Chemical Company. An analysis of stereochemical control in reactions of amide enolates derived from 2 together with complete experimental details will be presented in the ful1 paper resulting from this work.
(Received in USA 18 June 1984)