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Asymmetric diels-alder reaction of a chiral allenic ester : enantioselective synthesis of (−)-β-santalene
Tetrahedron Letters,Vo1.24,No.43,pp Printed in Great Britain
ASYMMETRIC
DIELS-ALDER
ENANTIOSELECTIVE
Wolfgang Departement
REACTION SYNTHESIS
de Chimie
:
OF A CHIRAL OF
ALLENIC ESTER (-)-f3-SANTALENE [ll
and Christian
Oppolzer*
CH-1211
oo40-4039/83 $3.00 + .Oo 01983 Pergamon Press Ltd.
4665-4668,1983
Organique,
Chapuis
Universite
de Geneve
Switzerland
Geneve,
Abstract. The Lewis-acid promoted Diels-Alder reaction of the allenic ester 10 provides the adduct 11 with excellent a-facial selection leading to an efficient enantioselective synthesis of (-)-i3-santalene and to the recovery of the chiral control element 7.
Asymmetric received
Diels-Alder
a great
quantitative
Scheme
deal of attention
diastereoface
cyclopentadiene (Scheme
reactions
addition
using chiral over the
differentiation 2 as recently -1 + -
dienophiles
last few years has been
achieved
reported
by this
or dienes [21 . Thus,
have almost
in the acrylate/ [31
laboratory
1). 1
,
CHzCI,
TiC12(0iPr),t-20’ 96% si -attack 99.3Kd.e.%$!=
1
The easy derived bias,
accessibility
control
offers
element,
attractive
y
2
of the rationally together
with
possibilities
designed,
recoverable,
its predictable for the synthesis
products.
4665
camphor-
and efficient of chiral
topological
natural
4666
In this context, we present here a highly enantioselective total synthesis of the olfactively interesting sandalwood constituent
(-)-S-santalene (6) [41 .
Its
[51
racemate has been synthesized elegantly by Bertrand et al. by means of a thermal allenic ester/cyclopentadiene addition 3 + 4 (Scheme 2) [61 . Scheme 2 aNaBH,,NiyH, @LDA
MeOOC
my
.
COOMe
II
(2) -4
3
(+I
_
5
R=COOMe
6
R=Me
Aiming at an efficient n-facial selection in the initial cycloaddition step, we have prepared the allenic ester -10 (Scheme 3). Scheme
3
R TFO
~C(Cl-q
7R=H 8 R = COCH,Br 9 R = COCH$ph,
0
CH,COCI NEt3 -
, CH#& sH
TiC11(0iPr)a,~200
COOR’
98%
53x
-4 QQX d.e.
10
~100%
es=
y
11
A’: J
/ 3
ffy~
*
OR 12R=H
(-)-p-Santalene
R’OH
3 7
QMe
13
R=CO+Co Ph
14
R=CONH
4667
of the chiral
Acylation
bromoester after
crystallization
yield
from 1). CH2C12,
Proceeding
O" -t 40°) gave after Torr)
salt
benzene, 80°, 15 h) furnished 9 I81 (m.p. 183-185O, 100%
[91 of 2 with acetyl chloride
reaction
distillation
the allenic
ester
(1 eq., NEt3 10 181 -
in 53% yield.
to the crucial
(3 eq.)
(1.06 eq.,
(CC14) the phosphonium
Wittig-type
(b.p. 145O/O.15
diene
(2 eq., AgCN 7 [31 with bromoacetyl bromide I71 followed by treatment of the resulting ,
benzene, 80°, 20 min) [81 with triphenylphosphine 2
(1.4 eq.),
(2 eq.),
alcohol
cycloaddition
in the presence
step,
of TiC12(GiPr)2
treatment
(1.5 eq.,
of -10 with
CH2C12,
-20°,
cyclopenta6 h)
t31
-11 [81 (oil) in 98% yield. To determine the diastereoof -11 it was reduced with LiA1H4 (excess, Et20, 200). The [81 contained only 2% of its exo-epimer (GC) which was resulting en&-alcohol -12 Acylation of pure 12 with (R)-(+)-a-methoxyreadily removed by preparative GC. 19 F-NMR a-trifluoromethylphenylacetic acid (1.5 eq., DCC (1.5 eq.), DMAP) and
afforded
the cycloadducts
isomeric
purity
[lo1 of the resulting
analysis
be enantiomerically naphthyl)-ethyl
Accordingly,
acid promoted follows the
Diels-Alder
addition
from the conversion
Selective
120°)
hydrogenation
of the resulting
and simple
40°) which (NH2NH2,
on successive afforded
sense
of induction
synthesis
(2), carried out along of racemic 6 [51 .
(EtOH) furnished
the pure ester -15 [8f 131 (m.p. 11911. Reduction of -15 with LiA1H4 (excess, Et 0) 2 element 7 and gave a crystalline alcohol [81 (m.p. 38-
oxidation
optically
(PCC, CH2C12)
and Wolff-Kishner
reduction
(-)-8-santalene (6). Synthetic t-)-2 was 13 [I31 , IR, 'H-NMR, ([a] C-NMR, MS) with (-)-8-santalene
identified
by comparison origin.
asymmetric
C,C-bond-formation
of practical
The absolute
(-)-8-santalene
of crude 11 (NaBH4, Ni(OAc)2, H2), subsequent a-alkyl[81 (l:LDA, 2:4-methyl-3-pentenyl iodide, THF/HMPA)
of natural
stage
10 + 11. --
of -11 into established
from crude
the auxiliary
KOH)
to
ester
crystallization
in 82% yield
refurnished
of N-N-dimethyl-2-aminoethanol
HPLC-analysis of -14 confirmed the 99% optical purity of -14. [121 has been achieved in the Lewisexcellent chiral efficiency
lines of the previously
ation
in the presence -
isocyanate['l'
give the carbamate 12.
ester -13 in the presence of Pr(fod)3 showed -12 to Alternatively, 12 was treated with (R)-(-)-l-(1-
pure.
We believe
pure
that
this work
by n-facial
applicability
[141
demonstrates
selection
convincingly
of enoates
that
has reached
the
.
Acknowledgements: Financial support of this work by the Swiss National Science Foundation, Sandoz Ltd, Basel, and Givaudan SA, Vernier is gratefully acknowledged. We also thank Mr. J.P. SauZnier, Mr. A. Pinto aid Mrs. D. Cle'ment for NMR and MS measurements.
4668
REFERENCES
AND NOTES
[II
To be presented at the 8th International Symposium Chemistry", Cambridge, England, July 1983.
[21
a) H.M. WaZborsky,L. Barash, T.C. Davis, Tetrahedron g,2333 (1963);J. Sauer, J. KredeZ, Tetrahedron Lett. 1966, 6359: R.F. Farmer, J. Hamer, J. Org. Chem. 31, 2418 (1966); E.J. Corey, H.E. EnsZey, J. Am. Chem. Sot. 97, 6908 (1975); R.K. Boeckman Jr., P.C. Naegely, S.D. Arthur, J. Org. Chem. 45, 752 (1980); D. Horton, T. Machinami, J. Chem. Sot. Chem. Commun. 88 (1981); G. HeZmchen, R. Schmierer, Angew. Chem. 93, 208 (1981); Angew. Chem. Int. Ed. Engl. 20, 205 (1981); W. OppoZzer, M. Kurtk, D. Reichlin, F. Moffatt, Tetrahedron Lett. 2545 (1981); W. Oppolzer, M. Kurth, D. ReichZin, c. Chapuis, M. Mohnhaupt, F. Moffatt, Helv. Chim. Acta 64, 2802 (1981); W. Choy, L.A. Reed III, S. Masamune, J. Org. Chem. 4&, 1137 (1983). b) B.M. Trost, S.A. Godleski, J.P. Gen&, J. Am. Chem. Sot. 100, 3930 (1978); B.M. Trost, D. O'KrongZy, J.L. BeZZetire, Ibid. 102, 7595 (1980); S. David, J. Eustache, A. Lubineau, J. Chem. Sot. Perkin I, 1795 (1979); W.G. Dauben, R.A. Bunce, Tetrahedron Lett. 1982, 4875; for an intramolecular asymmetric Diels-Alder reaction where the chirality-directing unit is attached to the chain which links the reaction partners see: T. Mukaiyama, N. Iwasawa, Chem. Lett. 29 (1981).
t31
W. Oppolaer, 1982, 4781.
141
Constitution: L. Ruzicka, G. Thomann, Helv. Chim. Acta 18, 355 (1935); configuration: C.R. Eck, G.L. Hodgson, D.F. MaeSweeney, R.W. MilZs, T. Money, J. Chem. Sot., Perkin Trans I, 1974, 1938.
[51
M. Bertrand,
[61
For other syntheses of santalenes and santalols see the reviews: G. Buehbauer, Chemiker-Zeitung 100, 225 (1976); E.-J. Brunke, E. KZein, in "Fragrance Chemistry", Ed. E.T. Theimer, Academic Press 1982, p. 397, and more recent work: K. Sato, 0. Miyamoto, S. Inoue, K. Honda, Chem. Lett. Lett. 1982, 947; 1981, 1183; H. Monti, C. Corriol, M. Bertrand, Tetrahedron rbid. 1982, 5539; D. SoZas, J. Wolinsky, J. Org. Chem. 48, 1988 (1983).
[71
S. Takimoto, J. Inanaga, T. Katsuki, M. Yamagushi, Bull. Chem. Sot. Jpn. 2, 2335 (1976). 1 H-N14R and mass spectra are in perfect agreement with the assigned IR, structure.
ial
[91
[lOI
C. Chapuis,
H. Monti,
M.D.
K.C.
Guo, D. Reichlin,
Huong,
Tetrahedron
"Synthesis
T. GodeZ,
Lett.
1979,
in Organic
Tetrahedron
Lett.
15.
R.W. Lang, H.-J. Hansen, Helv. Chim. Acta 63, 438 (1980). This preparation of the allenic ester -10 was superior to the approach described for the preparation of 3: M. Bertrand, Parfums, Cosmetiques, Aromes 2, 29 (1981). J.A. DaZe,
D.L. 0~11,
H.S. Mosher,
J. Org. Chem. 2,
2543
(1969).
Cl11
W.H. Pirkle,
[I21
implies chemical yield The term "chiral efficiency" of a reaction: J.M. Wilson, D.J. Cram, J. Am. Chem.
[131
The following compounds showed the indicated optical rotations [cxID : Is, -27.6O (c = 1.21, EtOH, 21.5'); synthetic c-j-5, -108.9' (c = 0.776, CHCl,, 200); natural (-)-5, -107.8' (C = 0.73, CHCl,, 20').
[I41
For highly asymmetric ene reactions and conjugate additions using chiral enoates see: W. OppoZzer, C. Robbiani, K. Bbttig, Helv. Chim. Acta 63, 2015 (1980); Tetrahedron 39 (1983) in press: W. Oppolzer, H. Liiher, Helv. Chim. Acta fi, 2808 (1981): (Received
J.R. Hauske,
in Germany
J. Org. Chem. 42,
18 July
1983)
1839
(1977). and asymmetric induction Sot. 109, 881 (1982).
ASYMMETRIC
DIELS-ALDER
ENANTIOSELECTIVE
Wolfgang Departement
REACTION SYNTHESIS
de Chimie
:
OF A CHIRAL OF
ALLENIC ESTER (-)-f3-SANTALENE [ll
and Christian
Oppolzer*
CH-1211
oo40-4039/83 $3.00 + .Oo 01983 Pergamon Press Ltd.
4665-4668,1983
Organique,
Chapuis
Universite
de Geneve
Switzerland
Geneve,
Abstract. The Lewis-acid promoted Diels-Alder reaction of the allenic ester 10 provides the adduct 11 with excellent a-facial selection leading to an efficient enantioselective synthesis of (-)-i3-santalene and to the recovery of the chiral control element 7.
Asymmetric received
Diels-Alder
a great
quantitative
Scheme
deal of attention
diastereoface
cyclopentadiene (Scheme
reactions
addition
using chiral over the
differentiation 2 as recently -1 + -
dienophiles
last few years has been
achieved
reported
by this
or dienes [21 . Thus,
have almost
in the acrylate/ [31
laboratory
1). 1
,
CHzCI,
TiC12(0iPr),t-20’ 96% si -attack 99.3Kd.e.%$!=
1
The easy derived bias,
accessibility
control
offers
element,
attractive
y
2
of the rationally together
with
possibilities
designed,
recoverable,
its predictable for the synthesis
products.
4665
camphor-
and efficient of chiral
topological
natural
4666
In this context, we present here a highly enantioselective total synthesis of the olfactively interesting sandalwood constituent
(-)-S-santalene (6) [41 .
Its
[51
racemate has been synthesized elegantly by Bertrand et al. by means of a thermal allenic ester/cyclopentadiene addition 3 + 4 (Scheme 2) [61 . Scheme 2 aNaBH,,NiyH, @LDA
MeOOC
my
.
COOMe
II
(2) -4
3
(+I
_
5
R=COOMe
6
R=Me
Aiming at an efficient n-facial selection in the initial cycloaddition step, we have prepared the allenic ester -10 (Scheme 3). Scheme
3
R TFO
~C(Cl-q
7R=H 8 R = COCH,Br 9 R = COCH$ph,
0
CH,COCI NEt3 -
, CH#& sH
TiC11(0iPr)a,~200
COOR’
98%
53x
-4 QQX d.e.
10
~100%
es=
y
11
A’: J
/ 3
ffy~
*
OR 12R=H
(-)-p-Santalene
R’OH
3 7
QMe
13
R=CO+Co Ph
14
R=CONH
4667
of the chiral
Acylation
bromoester after
crystallization
yield
from 1). CH2C12,
Proceeding
O" -t 40°) gave after Torr)
salt
benzene, 80°, 15 h) furnished 9 I81 (m.p. 183-185O, 100%
[91 of 2 with acetyl chloride
reaction
distillation
the allenic
ester
(1 eq., NEt3 10 181 -
in 53% yield.
to the crucial
(3 eq.)
(1.06 eq.,
(CC14) the phosphonium
Wittig-type
(b.p. 145O/O.15
diene
(2 eq., AgCN 7 [31 with bromoacetyl bromide I71 followed by treatment of the resulting ,
benzene, 80°, 20 min) [81 with triphenylphosphine 2
(1.4 eq.),
(2 eq.),
alcohol
cycloaddition
in the presence
step,
of TiC12(GiPr)2
treatment
(1.5 eq.,
of -10 with
CH2C12,
-20°,
cyclopenta6 h)
t31
-11 [81 (oil) in 98% yield. To determine the diastereoof -11 it was reduced with LiA1H4 (excess, Et20, 200). The [81 contained only 2% of its exo-epimer (GC) which was resulting en&-alcohol -12 Acylation of pure 12 with (R)-(+)-a-methoxyreadily removed by preparative GC. 19 F-NMR a-trifluoromethylphenylacetic acid (1.5 eq., DCC (1.5 eq.), DMAP) and
afforded
the cycloadducts
isomeric
purity
[lo1 of the resulting
analysis
be enantiomerically naphthyl)-ethyl
Accordingly,
acid promoted follows the
Diels-Alder
addition
from the conversion
Selective
120°)
hydrogenation
of the resulting
and simple
40°) which (NH2NH2,
on successive afforded
sense
of induction
synthesis
(2), carried out along of racemic 6 [51 .
(EtOH) furnished
the pure ester -15 [8f 131 (m.p. 11911. Reduction of -15 with LiA1H4 (excess, Et 0) 2 element 7 and gave a crystalline alcohol [81 (m.p. 38-
oxidation
optically
(PCC, CH2C12)
and Wolff-Kishner
reduction
(-)-8-santalene (6). Synthetic t-)-2 was 13 [I31 , IR, 'H-NMR, ([a] C-NMR, MS) with (-)-8-santalene
identified
by comparison origin.
asymmetric
C,C-bond-formation
of practical
The absolute
(-)-8-santalene
of crude 11 (NaBH4, Ni(OAc)2, H2), subsequent a-alkyl[81 (l:LDA, 2:4-methyl-3-pentenyl iodide, THF/HMPA)
of natural
stage
10 + 11. --
of -11 into established
from crude
the auxiliary
KOH)
to
ester
crystallization
in 82% yield
refurnished
of N-N-dimethyl-2-aminoethanol
HPLC-analysis of -14 confirmed the 99% optical purity of -14. [121 has been achieved in the Lewisexcellent chiral efficiency
lines of the previously
ation
in the presence -
isocyanate['l'
give the carbamate 12.
ester -13 in the presence of Pr(fod)3 showed -12 to Alternatively, 12 was treated with (R)-(-)-l-(1-
pure.
We believe
pure
that
this work
by n-facial
applicability
[141
demonstrates
selection
convincingly
of enoates
that
has reached
the
.
Acknowledgements: Financial support of this work by the Swiss National Science Foundation, Sandoz Ltd, Basel, and Givaudan SA, Vernier is gratefully acknowledged. We also thank Mr. J.P. SauZnier, Mr. A. Pinto aid Mrs. D. Cle'ment for NMR and MS measurements.
4668
REFERENCES
AND NOTES
[II
To be presented at the 8th International Symposium Chemistry", Cambridge, England, July 1983.
[21
a) H.M. WaZborsky,L. Barash, T.C. Davis, Tetrahedron g,2333 (1963);J. Sauer, J. KredeZ, Tetrahedron Lett. 1966, 6359: R.F. Farmer, J. Hamer, J. Org. Chem. 31, 2418 (1966); E.J. Corey, H.E. EnsZey, J. Am. Chem. Sot. 97, 6908 (1975); R.K. Boeckman Jr., P.C. Naegely, S.D. Arthur, J. Org. Chem. 45, 752 (1980); D. Horton, T. Machinami, J. Chem. Sot. Chem. Commun. 88 (1981); G. HeZmchen, R. Schmierer, Angew. Chem. 93, 208 (1981); Angew. Chem. Int. Ed. Engl. 20, 205 (1981); W. OppoZzer, M. Kurtk, D. Reichlin, F. Moffatt, Tetrahedron Lett. 2545 (1981); W. Oppolzer, M. Kurth, D. ReichZin, c. Chapuis, M. Mohnhaupt, F. Moffatt, Helv. Chim. Acta 64, 2802 (1981); W. Choy, L.A. Reed III, S. Masamune, J. Org. Chem. 4&, 1137 (1983). b) B.M. Trost, S.A. Godleski, J.P. Gen&, J. Am. Chem. Sot. 100, 3930 (1978); B.M. Trost, D. O'KrongZy, J.L. BeZZetire, Ibid. 102, 7595 (1980); S. David, J. Eustache, A. Lubineau, J. Chem. Sot. Perkin I, 1795 (1979); W.G. Dauben, R.A. Bunce, Tetrahedron Lett. 1982, 4875; for an intramolecular asymmetric Diels-Alder reaction where the chirality-directing unit is attached to the chain which links the reaction partners see: T. Mukaiyama, N. Iwasawa, Chem. Lett. 29 (1981).
t31
W. Oppolaer, 1982, 4781.
141
Constitution: L. Ruzicka, G. Thomann, Helv. Chim. Acta 18, 355 (1935); configuration: C.R. Eck, G.L. Hodgson, D.F. MaeSweeney, R.W. MilZs, T. Money, J. Chem. Sot., Perkin Trans I, 1974, 1938.
[51
M. Bertrand,
[61
For other syntheses of santalenes and santalols see the reviews: G. Buehbauer, Chemiker-Zeitung 100, 225 (1976); E.-J. Brunke, E. KZein, in "Fragrance Chemistry", Ed. E.T. Theimer, Academic Press 1982, p. 397, and more recent work: K. Sato, 0. Miyamoto, S. Inoue, K. Honda, Chem. Lett. Lett. 1982, 947; 1981, 1183; H. Monti, C. Corriol, M. Bertrand, Tetrahedron rbid. 1982, 5539; D. SoZas, J. Wolinsky, J. Org. Chem. 48, 1988 (1983).
[71
S. Takimoto, J. Inanaga, T. Katsuki, M. Yamagushi, Bull. Chem. Sot. Jpn. 2, 2335 (1976). 1 H-N14R and mass spectra are in perfect agreement with the assigned IR, structure.
ial
[91
[lOI
C. Chapuis,
H. Monti,
M.D.
K.C.
Guo, D. Reichlin,
Huong,
Tetrahedron
"Synthesis
T. GodeZ,
Lett.
1979,
in Organic
Tetrahedron
Lett.
15.
R.W. Lang, H.-J. Hansen, Helv. Chim. Acta 63, 438 (1980). This preparation of the allenic ester -10 was superior to the approach described for the preparation of 3: M. Bertrand, Parfums, Cosmetiques, Aromes 2, 29 (1981). J.A. DaZe,
D.L. 0~11,
H.S. Mosher,
J. Org. Chem. 2,
2543
(1969).
Cl11
W.H. Pirkle,
[I21
implies chemical yield The term "chiral efficiency" of a reaction: J.M. Wilson, D.J. Cram, J. Am. Chem.
[131
The following compounds showed the indicated optical rotations [cxID : Is, -27.6O (c = 1.21, EtOH, 21.5'); synthetic c-j-5, -108.9' (c = 0.776, CHCl,, 200); natural (-)-5, -107.8' (C = 0.73, CHCl,, 20').
[I41
For highly asymmetric ene reactions and conjugate additions using chiral enoates see: W. OppoZzer, C. Robbiani, K. Bbttig, Helv. Chim. Acta 63, 2015 (1980); Tetrahedron 39 (1983) in press: W. Oppolzer, H. Liiher, Helv. Chim. Acta fi, 2808 (1981): (Received
J.R. Hauske,
in Germany
J. Org. Chem. 42,
18 July
1983)
1839
(1977). and asymmetric induction Sot. 109, 881 (1982).