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Diastereoselective addition of a silylketene acetal to chiral α-thioaldehydes.
Tceahcdron Lcttm. Vo1.31. No.46. ~~6733-6736.1990 Printedin Great Britain
Diastereoselective
Addition
Rita Annunziata, Centro
cKMo-4039/90 $3.00 + .oo Pmgamon Re.ss plc
of a Silylketene
Mauro Cinquini,
CNR and Dipartimento
Acetal
Franc0 Cozzi,
di Chimica
Organica
Chirala-thioaldehydes of silylketene the ligands
represents
an efficient
give
diastereofacial
aldehyde
features
a highly
addition
alternative
process
ligand prone to chelation,
the
ligand
bearing
diastereoselective
Diastereoisomeric products
and
assignment
can
be
catalysts
confirmed
from
of
3
a
by
separating
the
correlation
conversion
case
out reacting
This methodology aldehydes.2
of
a chelating
addition
silylketene
with
obtained
the first
acetal,
the
a
from the use
were
we here report
When
L.a.
resulting
so far
can
are possible:
1,
1 and 2 to give 7a,b
to
with
study on chiral,
isomers of pure
by
flash
on the crude
chromatography.7
Structural
7a and 7b to the corresponding
epoxides
12a (J = 2.5 Hz), and from 7b -cis-epoxide
data
the
use
of
SnC14,
EtAlC12,
7a, while with MgBr2 and TiC14 -syn isomer of the stereochemical 3-6 (featuring
L.a. to give 8a,b-lla,b of
(Table 11.
by 300 MHz 'H-NMR spectroscopy
of 1 to&thioaldehydes
of selected
to epoxides
By examining
and of
respectively.
reported
product
the
ligands;2
from 7a trans-epoxide
the addition
for
addition
to aldehydes
two scenarios
reported
stereogenic
the
investigated
2. As
chiral
combination
of the data
non
To get a better understanding
Table
the
containing
good excess.
in the presence
to
stereocontrolled
Most
was carried
on chemical
to anti
from
acetals
aldol condensation.'
addition
(d.e.1 were evaluated
in the Scheme:
seen
exclusively
controlled
2-6 (Scheme).'
12b (J = 4.5 Hz) were obtained, As
L.a.
addition
excesses
resided
as-described
and/or
the
and silylketene
ligand at the stereocenter
or a discretely
4,5
racemic a-thioaldehydes
in
arising
oxygen or nitrogen
A survey of various
or non-chelation
on the nature of the Lewis acid catalyst
to the classic
selectivity
stereoselective
aldehydes
dell'universita
Italy.
of silyl enolethers
a heterosubstituted
of non-chelating
chelation
1, depending
Cozzi
at the stereocenter.
Lewis acid (L.a.) promoted
high
2-6 undergo
acetal
Pier Giorgio
e Industriale
Via Golgi 19, 20133 Milano,
Abstract.
to Chiral a-Thioaldehydes.
7a.b,
12a.b-13a,b
-300 MHz
(Scheme).
'H-NMR
6733
conclusions
BF3.Et20
led
7b was obtained
in
of this reaction
we
different
The results
spectroscopy,
allowed d.e. determination
the data of the Tables the following
outcome
and
R and R' groups) were
isomer
and structural can be drawn:
collected
separation,6 assignment.
in and
6734
X-
Me
Me
OSiMej
SK
+ R A CHO
SR
___t
a
R
Ax
SR C&Me
R
+
OMe
OH
1
2-6
13.212 R=Pr-i 4193 $10 6,11
COzMe
v
R=Pr-i R=Et R=Et R=Bn
R’=Ph R’=Me R’=Ph R’=Me R’=Ph
7b-llb
7a - lla
I
I
b, c, d
R&&OX
+
R&&OX B 12b- 13b
12a-l3a
X = SiPhzBu-l Reagents: a: see Tables 1 and 2. b: LiAlH,+ EbO, RT. c: l-BuPh.$iCl, Imidazole. DMF, RT. d: MqOBF.,. Chicly, RT; then 1N NaOH, RT. For all compounds only one enantiomer is shown for simplicity.
M ; ‘8 SR’
o
R’
%
@
*H 14
15
6735
Table 1. Diastereoselectivesynthesis of 7a.b by addition of 1 to 2.a
Entry
L.a.
Temperature,"C
Yield %b
7a:7bc
1
MgBrZd
-40
81
13:87
2
TiC14
-78
86
20:80
3
Zn12 e
25
60
45:55
4
SnC14
-78
78
298:
2
5
EtA1C12
-78
50
398: 2
6
BF3.Et2D
-78
87
a.98: 2
7
TBAFf
-78
30
75~25
a Unless otherwise stated all reactions were carried out on 0.5-1.0 nzaolscale in 5-10 ml of 6tlCl with a 1:1:1.5 2:L.a.:1 ratio for g-4 h. Entries 1, 3, 7 required HCl/NeOH wori-up. Used Tso3ated yields after chromatog;aphy. Determined as dycribed in the text. 1.1 mol equiv in THF. as 1M solution in Et2D/benzene. 0.05 mol equiv in CH3CN.
Table 2. Diastereoselectivesynthesis of &,b-1la.b by additSon of 1 to 3-6.a
Entry
Aldehyde
L.a.
Yield %
a:b
1
3
MgBr2
8a.b
61
10:90
2
3
TiC14
8a.b
76
7:93 48:52
Product
3
3
SnC14
8a.b
84
4
3
BF3.Et20
8a.b
90
5
4
MgBr2
9a.b
70
73:27
6
4
TiC14
9a.b
65
70:30
7
4
SnC14
9a.b
83
&98:
2
8
4
BF3.Et20
9a.b
71
398:
2
9
5
Ng8r2
1Oa.b
70
69:31
10
5
TiC14
1Oa.b
83
11:89
11
5
SnC14
1Da.b
91
50:50
12
5
BF3.Et20
1fla.b
72
13
6
MgBr2
lla,b
80
50:50
14
6
TiC14
lla,b
80
76~24
15
6
SnC14
lla,b
82
398: 2
16
6
BF3.Et20
lla,b
72
398: 2
398:
398:
2
2
a For experimental conditions, yields and d.e. determinations see Table 1 and text.
6736
1) Non-chelatingBF3.Et20 secures complete anti selectivity independentlyfrom the bulkiness of both R and R' groups. 2) SnCl4 acts as a non-chelating catalyst when R ’ = Ph, but leads to stereorandom reaction when R' = Me: in this case the less sterically requiring Me group allows some chelation at sulfur, and attack on both diastereofaces is possible.
3) Good chelation control (and appreciable excess of w
products) is obtained only with
chelating L.a., small R' group, -and large R group. On this basis we propose the two transition structures depicted in the Scheme. 1 as tentative rationals for this reaction. Felkin-Anh' t.s. 14 accounts for the formation of anti products, while Cram's cyclic' t.s. 15 should be at work when chelation is possible. Work is in progress to confirm this proposal, to extend this reaction to
stereogenic
silylketene acetals, and to evaluate the potentialities of a-thioaldehydes in other L.a. catalyzed reactions."
Acknowledgements.Financial support by M.P.I. - Roma is gratefully acknowledged.
References and Notes. T. Mukaiyama, K. Banno, K. Narasaka, J. Am. Chem. Sot., 96, 7503, 1974. Review: C. Gennari, Comprehensive Organic Synthesis: Selectivity for Synthetic Efficiency. C.H. Heathcock Ed., Pergamon Press, vol. 2, in press. Review on chelation/non-chelationstereocontrol: M.T. Reetz, Angew. Chem., Int. Ed. E?gl., 23, 556, 1984. J.H. Houn, R. Hermann, I. Ugi, Synthesis, 159, 1987. For other stereoselective reactions of a-thioaldehydes see: M. Shimagaki, H. Takuso, T. Oishi, Tetrahedron Lett., 6235, 1985;M. Shimagaki, T. Maeda, Y. Matsuzaki, I. Hori, T. Nakata, T. Oishi, Tetrahedron Lett., 4775, 1984; V.A. Aggarwal, I. Coldham,S. McIntyre, F.H. Sasbury, M.J. Villa, S. Warren, Tetrahedron Lett., 4885, 1988; I. Coldham, E.W. Collington, P. Hallett, S. Warren, Tetrahedron Lett., 5321, 1988. All new comppands gave analytical and spectral data in agreement with the proposed structure. Syn products were always eluted first than anti ones (9:l hexanes:diethylethermixture as xant ;Ar, 30.3, silica gel). N.T. Anh, Top. Curr. Chem., 88, 145, 1980; for the "large" role of an alkylthio group se& 'S.V.Frye, E.L. Eliel, J. Am. Chem. Sot., 110, 484, 1988; F. Bernardi, A. Bottoni, A.'Venturini, A. Mangini, J. Am. Chem. Sot., 108, 8171, 1986; H.J. Reich, R.C. Holtan, C. Bolm, J. Am. Chem. Sot., 112, 5609, 1990. E.L. Eliel, Asymmetric Synthesis, J.O. Morrison, Ed.; Wiley, vol. 2, p. 125, 1985. 10) BF3.Et20 catalyzed Hetero Diels-Alder cycloaddition of Danishefsky'sdiene to 5 followed by TFA work-up gave a highly 1d.e. = 96:4) stereoselectivereaction.
(Received in UK 31 August 1990)
Diastereoselective
Addition
Rita Annunziata, Centro
cKMo-4039/90 $3.00 + .oo Pmgamon Re.ss plc
of a Silylketene
Mauro Cinquini,
CNR and Dipartimento
Acetal
Franc0 Cozzi,
di Chimica
Organica
Chirala-thioaldehydes of silylketene the ligands
represents
an efficient
give
diastereofacial
aldehyde
features
a highly
addition
alternative
process
ligand prone to chelation,
the
ligand
bearing
diastereoselective
Diastereoisomeric products
and
assignment
can
be
catalysts
confirmed
from
of
3
a
by
separating
the
correlation
conversion
case
out reacting
This methodology aldehydes.2
of
a chelating
addition
silylketene
with
obtained
the first
acetal,
the
a
from the use
were
we here report
When
L.a.
resulting
so far
can
are possible:
1,
1 and 2 to give 7a,b
to
with
study on chiral,
isomers of pure
by
flash
on the crude
chromatography.7
Structural
7a and 7b to the corresponding
epoxides
12a (J = 2.5 Hz), and from 7b -cis-epoxide
data
the
use
of
SnC14,
EtAlC12,
7a, while with MgBr2 and TiC14 -syn isomer of the stereochemical 3-6 (featuring
L.a. to give 8a,b-lla,b of
(Table 11.
by 300 MHz 'H-NMR spectroscopy
of 1 to&thioaldehydes
of selected
to epoxides
By examining
and of
respectively.
reported
product
the
ligands;2
from 7a trans-epoxide
the addition
for
addition
to aldehydes
two scenarios
reported
stereogenic
the
investigated
2. As
chiral
combination
of the data
non
To get a better understanding
Table
the
containing
good excess.
in the presence
to
stereocontrolled
Most
was carried
on chemical
to anti
from
acetals
aldol condensation.'
addition
(d.e.1 were evaluated
in the Scheme:
seen
exclusively
controlled
2-6 (Scheme).'
12b (J = 4.5 Hz) were obtained, As
L.a.
addition
excesses
resided
as-described
and/or
the
and silylketene
ligand at the stereocenter
or a discretely
4,5
racemic a-thioaldehydes
in
arising
oxygen or nitrogen
A survey of various
or non-chelation
on the nature of the Lewis acid catalyst
to the classic
selectivity
stereoselective
aldehydes
dell'universita
Italy.
of silyl enolethers
a heterosubstituted
of non-chelating
chelation
1, depending
Cozzi
at the stereocenter.
Lewis acid (L.a.) promoted
high
2-6 undergo
acetal
Pier Giorgio
e Industriale
Via Golgi 19, 20133 Milano,
Abstract.
to Chiral a-Thioaldehydes.
7a.b,
12a.b-13a,b
-300 MHz
(Scheme).
'H-NMR
6733
conclusions
BF3.Et20
led
7b was obtained
in
of this reaction
we
different
The results
spectroscopy,
allowed d.e. determination
the data of the Tables the following
outcome
and
R and R' groups) were
isomer
and structural can be drawn:
collected
separation,6 assignment.
in and
6734
X-
Me
Me
OSiMej
SK
+ R A CHO
SR
___t
a
R
Ax
SR C&Me
R
+
OMe
OH
1
2-6
13.212 R=Pr-i 4193 $10 6,11
COzMe
v
R=Pr-i R=Et R=Et R=Bn
R’=Ph R’=Me R’=Ph R’=Me R’=Ph
7b-llb
7a - lla
I
I
b, c, d
R&&OX
+
R&&OX B 12b- 13b
12a-l3a
X = SiPhzBu-l Reagents: a: see Tables 1 and 2. b: LiAlH,+ EbO, RT. c: l-BuPh.$iCl, Imidazole. DMF, RT. d: MqOBF.,. Chicly, RT; then 1N NaOH, RT. For all compounds only one enantiomer is shown for simplicity.
M ; ‘8 SR’
o
R’
%
@
*H 14
15
6735
Table 1. Diastereoselectivesynthesis of 7a.b by addition of 1 to 2.a
Entry
L.a.
Temperature,"C
Yield %b
7a:7bc
1
MgBrZd
-40
81
13:87
2
TiC14
-78
86
20:80
3
Zn12 e
25
60
45:55
4
SnC14
-78
78
298:
2
5
EtA1C12
-78
50
398: 2
6
BF3.Et2D
-78
87
a.98: 2
7
TBAFf
-78
30
75~25
a Unless otherwise stated all reactions were carried out on 0.5-1.0 nzaolscale in 5-10 ml of 6tlCl with a 1:1:1.5 2:L.a.:1 ratio for g-4 h. Entries 1, 3, 7 required HCl/NeOH wori-up. Used Tso3ated yields after chromatog;aphy. Determined as dycribed in the text. 1.1 mol equiv in THF. as 1M solution in Et2D/benzene. 0.05 mol equiv in CH3CN.
Table 2. Diastereoselectivesynthesis of &,b-1la.b by additSon of 1 to 3-6.a
Entry
Aldehyde
L.a.
Yield %
a:b
1
3
MgBr2
8a.b
61
10:90
2
3
TiC14
8a.b
76
7:93 48:52
Product
3
3
SnC14
8a.b
84
4
3
BF3.Et20
8a.b
90
5
4
MgBr2
9a.b
70
73:27
6
4
TiC14
9a.b
65
70:30
7
4
SnC14
9a.b
83
&98:
2
8
4
BF3.Et20
9a.b
71
398:
2
9
5
Ng8r2
1Oa.b
70
69:31
10
5
TiC14
1Oa.b
83
11:89
11
5
SnC14
1Da.b
91
50:50
12
5
BF3.Et20
1fla.b
72
13
6
MgBr2
lla,b
80
50:50
14
6
TiC14
lla,b
80
76~24
15
6
SnC14
lla,b
82
398: 2
16
6
BF3.Et20
lla,b
72
398: 2
398:
398:
2
2
a For experimental conditions, yields and d.e. determinations see Table 1 and text.
6736
1) Non-chelatingBF3.Et20 secures complete anti selectivity independentlyfrom the bulkiness of both R and R' groups. 2) SnCl4 acts as a non-chelating catalyst when R ’ = Ph, but leads to stereorandom reaction when R' = Me: in this case the less sterically requiring Me group allows some chelation at sulfur, and attack on both diastereofaces is possible.
3) Good chelation control (and appreciable excess of w
products) is obtained only with
chelating L.a., small R' group, -and large R group. On this basis we propose the two transition structures depicted in the Scheme. 1 as tentative rationals for this reaction. Felkin-Anh' t.s. 14 accounts for the formation of anti products, while Cram's cyclic' t.s. 15 should be at work when chelation is possible. Work is in progress to confirm this proposal, to extend this reaction to
stereogenic
silylketene acetals, and to evaluate the potentialities of a-thioaldehydes in other L.a. catalyzed reactions."
Acknowledgements.Financial support by M.P.I. - Roma is gratefully acknowledged.
References and Notes. T. Mukaiyama, K. Banno, K. Narasaka, J. Am. Chem. Sot., 96, 7503, 1974. Review: C. Gennari, Comprehensive Organic Synthesis: Selectivity for Synthetic Efficiency. C.H. Heathcock Ed., Pergamon Press, vol. 2, in press. Review on chelation/non-chelationstereocontrol: M.T. Reetz, Angew. Chem., Int. Ed. E?gl., 23, 556, 1984. J.H. Houn, R. Hermann, I. Ugi, Synthesis, 159, 1987. For other stereoselective reactions of a-thioaldehydes see: M. Shimagaki, H. Takuso, T. Oishi, Tetrahedron Lett., 6235, 1985;M. Shimagaki, T. Maeda, Y. Matsuzaki, I. Hori, T. Nakata, T. Oishi, Tetrahedron Lett., 4775, 1984; V.A. Aggarwal, I. Coldham,S. McIntyre, F.H. Sasbury, M.J. Villa, S. Warren, Tetrahedron Lett., 4885, 1988; I. Coldham, E.W. Collington, P. Hallett, S. Warren, Tetrahedron Lett., 5321, 1988. All new comppands gave analytical and spectral data in agreement with the proposed structure. Syn products were always eluted first than anti ones (9:l hexanes:diethylethermixture as xant ;Ar, 30.3, silica gel). N.T. Anh, Top. Curr. Chem., 88, 145, 1980; for the "large" role of an alkylthio group se& 'S.V.Frye, E.L. Eliel, J. Am. Chem. Sot., 110, 484, 1988; F. Bernardi, A. Bottoni, A.'Venturini, A. Mangini, J. Am. Chem. Sot., 108, 8171, 1986; H.J. Reich, R.C. Holtan, C. Bolm, J. Am. Chem. Sot., 112, 5609, 1990. E.L. Eliel, Asymmetric Synthesis, J.O. Morrison, Ed.; Wiley, vol. 2, p. 125, 1985. 10) BF3.Et20 catalyzed Hetero Diels-Alder cycloaddition of Danishefsky'sdiene to 5 followed by TFA work-up gave a highly 1d.e. = 96:4) stereoselectivereaction.
(Received in UK 31 August 1990)