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Reductive ring openings of allyl-alcohol epoxides
Tetrahedron Letters,Vo1.23,No.27,pp Prmted m Great Brltam
REDUCTIVE
2719-2722,1982
RING OPENINGS
0040-4039/82/272719-04$03.00/O 01982 Pergamon Press Ltd.
OF ALLYL-ALCOHOL
EPOXIDES
James M. Finan and Yoshito Klshi* of Chemistry, Harvard Unlverslty, Cambridge,
Department
Mass.
02138, U.S.A
Red-Al reduction of allyl-alcohol epoxldes was shown to yield 1,3-dlols regloselectlvlty, while DIBAL reduction was shown to yield 1,2-dlols.
Abstract
A 1,3_polyhydroxylated lncludlng
polyene
macrollde
chain 1s often 1
been no general method
for syntheslzlng
In th1.s communication,
we would
Encouraged polyether
by successful
the feaslblllty
such a system
like to report
of Important
natural products
to the best of our knowledge,
there has
In a reglo- and stereocontrolled
a sunple
solution
fashlon.2
for this problem.
application
anssmycln
antlblotlcs3,
found on the backbone However,
antlblotlcs.
In high
of the synthetic
of the chain extension approach for the synthesis of 5 4 antlblotlcs , and carbohydrates , It was decided to examine
approach
shown below,
consisting
of a repetltlon
of two mayor
steps, l.e., A and B. With respect to step A, Sharpless asymmetric epoxldatlon of allyllc 6 seemed to provide a practical and reliable method of synthesizing either R- or Salcohols epoxldes
Thus,
we began to study a selective method to achieve step g.
of epoxlde _? 1
of the ring opening the results
summarized
tions satisfy
purposes.
trvlty seems to be the hydroxy
addltlonal
substrates
In contrast
seemed
this seems to be a general
reaCtlOn
exclusively'
case, DIBAL reduction Although
the expected
the alcohol 5. (Red-Al/THF/OOC)
1,3-dlols
of the epoxlde 1 yielded
the degree
of regloselectlvlty
asymmetric
epoxidatlon,
route to 1,3_polyhydroxylated
using
the Red-Al
The stereoselectlvity
(I-PrO)2P(0)CH2C02Et10
reduction
systems , as demonstrated
The of three yield.
the 1,2-dial 2
varies by substrate,
provides
on the three
a stereo-
In the synthesis
of the Horner-Emmons
was 98:2 or better.
under
In excellent
trend, the results
the alcohols -17 and 19 (see scheme) of Wlttlg
exclusively*
condi-
regioselec-
unchanged
of DIBAL ring openzng (DIBAL/C6H6/RT) 9 -7 through -9 are lndlcated in the structures.
Cou,rled with Sharpless and reglocontrolled
this remarkable
the epoxlde 4 was recovered
the epoxide 2 ylelded
From
[NaAlH2(OCH2CH20CH3)21
to be very good, the Red-Al ring opening
(see table).
substrates
reagents was examined.
factor controlling
group in 1, because
? through 2 yielded
to the Red-Al
as the mayor product
addltlonal
The primary
and also because
scope of this reaction
hydride
In the table , It IS clear that the Red-Al
the present
the same condltlons
(racemlc) by various
The regloselectlvlty
of
modlflcation
The Red-Al reduction of the 8 products exclusively The optlcal 11 purity of the epoxlde -12 and the alcohol -13 was very high However, asymmetric lnductlon In the epoxldatlon of the allyllc alcohol -15 by using either natural (+)- or unnatural (-)-dlethyl epoxldes
12, -16 and -18 ylelded
the expected
1,3-dihydroxy
2719
9
2720
R’“-Y-oR2 F?o~od OH
1: 1 - R 'CH2C6H5,
R =n
4. R 1=Cn2C6n5,
2 R =Me
2
1
1
R =CH2C6H5,
2 R =H
-3 l2 R1=cnc2 6 n 5t R2=H 6.12 R1=H _.
c n I R2=CH 265
5. R 1=n, R 2 =CH2C6H5
OH
4
BzlO
7
BzlO&OH
0
Red-Al
= >20:18'14
DIBAL
=
9: Red-Al
g: Red-Al = >20.18'14
1 1 213.14
DIBAL
=
1 . 613,14
DIBAL
= >20 18'14 =
1 . 813,14
- -
Table
6210
OH
-
+
B*‘“-oH OH -212
-1
Product Reagent
h!o&OH
and Reaction
Conditions
-2
Ratio
:3 -
Red-Al/benzene/RT
19
-
Red-Al/ether/RT
12
:
1
Red-Al/THF/RT
22
.
1
Red-Al/TH!?/O'C
40
-
1
Red-Al/THF/-2O'C
150
:
1
1
DIBAL/hexane/RT
1:7
DIBAL/benzene/RT
1
DIBAL/ether/RT
1.7
DIBAL/ether/O'C
1
5
DIBAL/ether/-20°C
1
3
LAH/ether/RT
1:l
LAH/THF/RT
1.1
13
13
312 -
2721
Scheme First Chain-Extension
-11
Second Chain-Extension
OH d
1,12,14,15 -
-16 Y'p
YYO
."o-O"
?z
S"O~
\
OH
-15
-14
f
e I-
1912,14.15 -
-18
Reagents a.
03/MeOH-CH2C12;-780C,
followed
by
(Me)2S work-up
(l-Pro) P(O)CH CO Et/t-BuOK/THF/-78OC DIBAL,TiF,-78 0:: 2
d.
t-BuOOH/(+)-dlethyl
tartrate/(~-PrO)4T~/CH2C12/-230C6
-e.
t-BuOOH/(-)-diethyl
tartrate/(l-PrO)4T1/CH2C12/-230C6
-f.
Red-Al/THF/O'C
4
(t-Bu) (C6H5)2S~Cl/lmldazole/DMF/RT
h. -
tartrate
yIelded
Improvement
+ O°C1o
::
MeOCH2Br/(l-Pr)2(Et)N/cH2c12/RT
-1.
(n-Buj4NF/THF/RT
1.
DMSO/(COCl)2/CH2C12/-600C,
about a 3 1 mixture
of this step by changing
and then Et3N
16
of the two dlastereomers the protecting
We are currently
group of the secondary
lnvestlgatlng
alcoholic
group of
-15. Although the observed duclng
further results,
experiments the Red-Al
agent with the alcoholic
DIBAL reduction In which
~111 be necessary reduction
group,
also seems to Involve
the aluminum
to provide
seems to involve
followed lnltlal
by intramolecular
formatzon
to the practical
hydroxylated
systems
(cf.
appllcatlon,
explanation
complexatlon
hydride
lntennolecular
reduction.
It seems worth polntlng
hydride
out that 1,4-
for
of the reThe
of a complex with the alcoholic
serves as a Lewis acid to facllltate
With respect
a mechanlstlc
lnltlal
group,
reduction. (or 1,2-) dl-
2 and 5) could also be obtained by either the Red-Al or DIBAL method.
2722
Acknowledgment the National
Flnanclal Science
assistance
Foundation
from the Natlonal
(CHE 78-06296) References
(1) For example, a.,
see W. Mechlinskl,
3873
related
Chem. Sot., 2,
A. W. Fritz. (1980), G
262
(NS 12108) and
and Footnotes
Schaffner,
4829
to this problem,
P. Ganls and G. Avltabzle,
M. Clmarustl, Lett., 2847
Tetrahedron
Cardlllo, S
see P. A. Bartlett
(1977), P. A. Bartlett
(1980), D. M. Floyd and C
Akasaka,
of Health
acknowledged.
Tetrahedron
(1970).
(2) For some works
(3) Y. lushl,
C. P
Institutes
is gratefully
and K
and M
D. J. Karanewsky,
K. Jernstedt,
Tetrahedron
Sandra,
J. Wang, G
J. Am.
Lett.,
1607
(1979), D. M. Floyd and
and H. C. Pal, Chem. Lett.,
J. C. S. Chem. Comm., 465
D. Lewis, Pure Appl. Chem
C.-L
Jernstedt,
Tetrahedron
, 4129
Lett
(1981)‘ K. Narasaka
M. Orena, G. Porzl and S
Hatakeyama
and K. K
, In press,
1415
(1981).
T. Fukuyama,
K.
Schmld and Y. I
(1979).
(4) H. Nagaoka, W. Rutsch, G. Schmld, H. ILO, M. R. Johnson and Y. tishl, J. Am. Chem. Sot., -102, 7962
(1980), H. Nagaoka
Appl. Chem
, 53, 1163
and Y. Iclshl, Tetrahedron,
(5) N. Mlnaml,
S. S. Ko and Y. IClshl, J
(6) T. Katsukl
and K. B. Sharpless,
trlbution Woodard,
to this method
spectroscopic
Sharpless
which
(11) OptIcal prepared
of -14 was examined
according
(1982).
(1980).
The most recent con-
1s found In V. S. Martin,
S
S
J. Am. Chem. Sot., -103, 6237
of this paper
for all new compounds
was greater
than 2O:l
described
In this paper
(NMR). examples
respectively,
In USA
of Its MTPA derivative, 2543
(1969)l
No minor
ylelded
an aldehyde,
but the alcoho IS
unchanged.
by HPLC analysis
the product
(TFA/CH~C~~/RT)
which were easily
(16) A. J. Mancuso,
[J. Org. Chem., 4,
the alcohol 2 smoothly
-17 and 19 were recovered
(15) On acid treatment
4.
by these analyses.
treatment,
(14) This ratlo represents
under reference
by H-NMR and F-NMR analyses
to the Mosher procedure
was detected
(13) The ratlo was determined
(Received
1109 5974
tlus statement.
(12) On sodium perlodate 2, 5, 2,
(1981), Y. Klshl, e
In OUT laboratorles , we have found numerous
7 of the second paper quoted
purity
enantlomer
zor a preprint
reglolsomers
with other research
support
Sot., E,
laboratory
data were obtained
f8) The ratlo of the two possible
(10) See footnote
3873
Y. Yamada, M. Ikeda and K. B. Sharpless,
T. Katsukl,
(9) In connection
Am. Chem
J. Am. Chem. Sot., 102,
from the Sharpless
(1981), we thank PrJ:essor (7) Satisfactory
2,
(1981)
1982)
and 1,2-dlol.
the alcohols 11 and 19 ylelded
separable
S -L. Juang and D
30 March
ratlo of 1,3-dlol
the acetals + and 11,
by slllca gel thin layer chromatography.
Swern, J. Org. Chem
, 2,
2480
(1978)
REDUCTIVE
2719-2722,1982
RING OPENINGS
0040-4039/82/272719-04$03.00/O 01982 Pergamon Press Ltd.
OF ALLYL-ALCOHOL
EPOXIDES
James M. Finan and Yoshito Klshi* of Chemistry, Harvard Unlverslty, Cambridge,
Department
Mass.
02138, U.S.A
Red-Al reduction of allyl-alcohol epoxldes was shown to yield 1,3-dlols regloselectlvlty, while DIBAL reduction was shown to yield 1,2-dlols.
Abstract
A 1,3_polyhydroxylated lncludlng
polyene
macrollde
chain 1s often 1
been no general method
for syntheslzlng
In th1.s communication,
we would
Encouraged polyether
by successful
the feaslblllty
such a system
like to report
of Important
natural products
to the best of our knowledge,
there has
In a reglo- and stereocontrolled
a sunple
solution
fashlon.2
for this problem.
application
anssmycln
antlblotlcs3,
found on the backbone However,
antlblotlcs.
In high
of the synthetic
of the chain extension approach for the synthesis of 5 4 antlblotlcs , and carbohydrates , It was decided to examine
approach
shown below,
consisting
of a repetltlon
of two mayor
steps, l.e., A and B. With respect to step A, Sharpless asymmetric epoxldatlon of allyllc 6 seemed to provide a practical and reliable method of synthesizing either R- or Salcohols epoxldes
Thus,
we began to study a selective method to achieve step g.
of epoxlde _? 1
of the ring opening the results
summarized
tions satisfy
purposes.
trvlty seems to be the hydroxy
addltlonal
substrates
In contrast
seemed
this seems to be a general
reaCtlOn
exclusively'
case, DIBAL reduction Although
the expected
the alcohol 5. (Red-Al/THF/OOC)
1,3-dlols
of the epoxlde 1 yielded
the degree
of regloselectlvlty
asymmetric
epoxidatlon,
route to 1,3_polyhydroxylated
using
the Red-Al
The stereoselectlvity
(I-PrO)2P(0)CH2C02Et10
reduction
systems , as demonstrated
The of three yield.
the 1,2-dial 2
varies by substrate,
provides
on the three
a stereo-
In the synthesis
of the Horner-Emmons
was 98:2 or better.
under
In excellent
trend, the results
the alcohols -17 and 19 (see scheme) of Wlttlg
exclusively*
condi-
regioselec-
unchanged
of DIBAL ring openzng (DIBAL/C6H6/RT) 9 -7 through -9 are lndlcated in the structures.
Cou,rled with Sharpless and reglocontrolled
this remarkable
the epoxlde 4 was recovered
the epoxide 2 ylelded
From
[NaAlH2(OCH2CH20CH3)21
to be very good, the Red-Al ring opening
(see table).
substrates
reagents was examined.
factor controlling
group in 1, because
? through 2 yielded
to the Red-Al
as the mayor product
addltlonal
The primary
and also because
scope of this reaction
hydride
In the table , It IS clear that the Red-Al
the present
the same condltlons
(racemlc) by various
The regloselectlvlty
of
modlflcation
The Red-Al reduction of the 8 products exclusively The optlcal 11 purity of the epoxlde -12 and the alcohol -13 was very high However, asymmetric lnductlon In the epoxldatlon of the allyllc alcohol -15 by using either natural (+)- or unnatural (-)-dlethyl epoxldes
12, -16 and -18 ylelded
the expected
1,3-dihydroxy
2719
9
2720
R’“-Y-oR2 F?o~od OH
1: 1 - R 'CH2C6H5,
R =n
4. R 1=Cn2C6n5,
2 R =Me
2
1
1
R =CH2C6H5,
2 R =H
-3 l2 R1=cnc2 6 n 5t R2=H 6.12 R1=H _.
c n I R2=CH 265
5. R 1=n, R 2 =CH2C6H5
OH
4
BzlO
7
BzlO&OH
0
Red-Al
= >20:18'14
DIBAL
=
9: Red-Al
g: Red-Al = >20.18'14
1 1 213.14
DIBAL
=
1 . 613,14
DIBAL
= >20 18'14 =
1 . 813,14
- -
Table
6210
OH
-
+
B*‘“-oH OH -212
-1
Product Reagent
h!o&OH
and Reaction
Conditions
-2
Ratio
:3 -
Red-Al/benzene/RT
19
-
Red-Al/ether/RT
12
:
1
Red-Al/THF/RT
22
.
1
Red-Al/TH!?/O'C
40
-
1
Red-Al/THF/-2O'C
150
:
1
1
DIBAL/hexane/RT
1:7
DIBAL/benzene/RT
1
DIBAL/ether/RT
1.7
DIBAL/ether/O'C
1
5
DIBAL/ether/-20°C
1
3
LAH/ether/RT
1:l
LAH/THF/RT
1.1
13
13
312 -
2721
Scheme First Chain-Extension
-11
Second Chain-Extension
OH d
1,12,14,15 -
-16 Y'p
YYO
."o-O"
?z
S"O~
\
OH
-15
-14
f
e I-
1912,14.15 -
-18
Reagents a.
03/MeOH-CH2C12;-780C,
followed
by
(Me)2S work-up
(l-Pro) P(O)CH CO Et/t-BuOK/THF/-78OC DIBAL,TiF,-78 0:: 2
d.
t-BuOOH/(+)-dlethyl
tartrate/(~-PrO)4T~/CH2C12/-230C6
-e.
t-BuOOH/(-)-diethyl
tartrate/(l-PrO)4T1/CH2C12/-230C6
-f.
Red-Al/THF/O'C
4
(t-Bu) (C6H5)2S~Cl/lmldazole/DMF/RT
h. -
tartrate
yIelded
Improvement
+ O°C1o
::
MeOCH2Br/(l-Pr)2(Et)N/cH2c12/RT
-1.
(n-Buj4NF/THF/RT
1.
DMSO/(COCl)2/CH2C12/-600C,
about a 3 1 mixture
of this step by changing
and then Et3N
16
of the two dlastereomers the protecting
We are currently
group of the secondary
lnvestlgatlng
alcoholic
group of
-15. Although the observed duclng
further results,
experiments the Red-Al
agent with the alcoholic
DIBAL reduction In which
~111 be necessary reduction
group,
also seems to Involve
the aluminum
to provide
seems to involve
followed lnltlal
by intramolecular
formatzon
to the practical
hydroxylated
systems
(cf.
appllcatlon,
explanation
complexatlon
hydride
lntennolecular
reduction.
It seems worth polntlng
hydride
out that 1,4-
for
of the reThe
of a complex with the alcoholic
serves as a Lewis acid to facllltate
With respect
a mechanlstlc
lnltlal
group,
reduction. (or 1,2-) dl-
2 and 5) could also be obtained by either the Red-Al or DIBAL method.
2722
Acknowledgment the National
Flnanclal Science
assistance
Foundation
from the Natlonal
(CHE 78-06296) References
(1) For example, a.,
see W. Mechlinskl,
3873
related
Chem. Sot., 2,
A. W. Fritz. (1980), G
262
(NS 12108) and
and Footnotes
Schaffner,
4829
to this problem,
P. Ganls and G. Avltabzle,
M. Clmarustl, Lett., 2847
Tetrahedron
Cardlllo, S
see P. A. Bartlett
(1977), P. A. Bartlett
(1980), D. M. Floyd and C
Akasaka,
of Health
acknowledged.
Tetrahedron
(1970).
(2) For some works
(3) Y. lushl,
C. P
Institutes
is gratefully
and K
and M
D. J. Karanewsky,
K. Jernstedt,
Tetrahedron
Sandra,
J. Wang, G
J. Am.
Lett.,
1607
(1979), D. M. Floyd and
and H. C. Pal, Chem. Lett.,
J. C. S. Chem. Comm., 465
D. Lewis, Pure Appl. Chem
C.-L
Jernstedt,
Tetrahedron
, 4129
Lett
(1981)‘ K. Narasaka
M. Orena, G. Porzl and S
Hatakeyama
and K. K
, In press,
1415
(1981).
T. Fukuyama,
K.
Schmld and Y. I
(1979).
(4) H. Nagaoka, W. Rutsch, G. Schmld, H. ILO, M. R. Johnson and Y. tishl, J. Am. Chem. Sot., -102, 7962
(1980), H. Nagaoka
Appl. Chem
, 53, 1163
and Y. Iclshl, Tetrahedron,
(5) N. Mlnaml,
S. S. Ko and Y. IClshl, J
(6) T. Katsukl
and K. B. Sharpless,
trlbution Woodard,
to this method
spectroscopic
Sharpless
which
(11) OptIcal prepared
of -14 was examined
according
(1982).
(1980).
The most recent con-
1s found In V. S. Martin,
S
S
J. Am. Chem. Sot., -103, 6237
of this paper
for all new compounds
was greater
than 2O:l
described
In this paper
(NMR). examples
respectively,
In USA
of Its MTPA derivative, 2543
(1969)l
No minor
ylelded
an aldehyde,
but the alcoho IS
unchanged.
by HPLC analysis
the product
(TFA/CH~C~~/RT)
which were easily
(16) A. J. Mancuso,
[J. Org. Chem., 4,
the alcohol 2 smoothly
-17 and 19 were recovered
(15) On acid treatment
4.
by these analyses.
treatment,
(14) This ratlo represents
under reference
by H-NMR and F-NMR analyses
to the Mosher procedure
was detected
(13) The ratlo was determined
(Received
1109 5974
tlus statement.
(12) On sodium perlodate 2, 5, 2,
(1981), Y. Klshl, e
In OUT laboratorles , we have found numerous
7 of the second paper quoted
purity
enantlomer
zor a preprint
reglolsomers
with other research
support
Sot., E,
laboratory
data were obtained
f8) The ratlo of the two possible
(10) See footnote
3873
Y. Yamada, M. Ikeda and K. B. Sharpless,
T. Katsukl,
(9) In connection
Am. Chem
J. Am. Chem. Sot., 102,
from the Sharpless
(1981), we thank PrJ:essor (7) Satisfactory
2,
(1981)
1982)
and 1,2-dlol.
the alcohols 11 and 19 ylelded
separable
S -L. Juang and D
30 March
ratlo of 1,3-dlol
the acetals + and 11,
by slllca gel thin layer chromatography.
Swern, J. Org. Chem
, 2,
2480
(1978)