Remote asymmetric induction using acetate-type vinylketene silyl N,O-acetals

Article abstract of DOI:10.1021/acs.orglett.6b03476

Remote asymmetric induction by the vinylogous Mukaiyama aldol reaction using the acetate-type vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved. The silyl N,O-acetal derived from crotonate and L-valine afforded the O-silylated 5

Full text of DOI:10.1021/acs.orglett.6b03476

Letter
pubs.acs.org/OrgLett
Remote Asymmetric Induction Using Acetate-Type Vinylketene
Silyl N,O‑Acetals
Naoya Sagawa, Haruka Sato, and Seijiro Hosokawa*
Department of Applied Chemistry, Faculty of Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku,
Tokyo 169-8555, Japan
S
* Supporting Information
ABSTRACT: Remote asymmetric induction by the vinyl-
ogous Mukaiyama aldol reaction using the acetate-type
vinylketene silyl N,O-acetal possessing a chiral auxiliary has
been achieved. The silyl N,O-acetal derived from crotonate
and L-valine afforded the O-silylated 5R- and 5S-adducts
selectively by treatment with SnCl4 and BF3·OEt2, respectively.
The SnCl4-mediated isomerization of silyl dienol ether was
found, and the resulting major isomer showed high reactivity to give γ-adduct in high stereoselectivity.
emote asymmetric induction reactions have been studied
as challenging matters in organic chemistry.1 Although a
of this reaction would give a new methodology to construct the
polyacetate skeleton in short step. Herein, we present improved
vinylogous Mukaiyama aldol reactions using newly designed
chiral dienolates.
The X-ray crystallograph of 1a is disclosed in Figure 1. The
oxazolidone ring places almost perpendicular to the diene chain
R
limited number of systems have been developed, they have been
used as powerful tools in natural product syntheses.2 During the
course of our research on methodologies and strategies to realize
the short-step synthesis of polyketides, we have developed
remote asymmetric induction reactions using the vinylketene
silyl N,O-acetals 1a and 1b (Scheme 1, eq 1).3 This reaction
Scheme 1. Previous Results on Remote Asymmetric Induction
Using Vinylketene Silyl N,O-Acetals3a
Figure 1. Conformation of 1a: (A) ORTEP drawing of crystal 1a;
(B) NOE correlation of 1a in CDCl3.
(Figure 1A). This conformation does not allow participation of
the lone-pair electron of nitrogen to the diene, which is a reason
for the stability of 1a. The oxazolidone ring looks impossible to
rotate because it is sandwiched between a methyl group of TBS
and the dienol side chain. One of methyl groups of the isopropyl
group overlaps the tetrasubstituted olefin. A similar conforma-
tion of 1a in CDCl3 solution was observed by NOE correlation
between H3 and the methyl group of the isopropyl group
(Figure 1B).
On the other hand, direction of extension of the side chain of 3
(Scheme 1, eq 2) was different from that of 1a. The terminal
carbon of the diene 3, the reaction site, should be far from
isopropyl group on the oxazolidone ring. To improve the
direction of the isopropyl group and stability of dienol ether,
we designed new vinylketene N,O-acetal as 5 shown in Figure 2.
When the chiral auxiliary attaches to the dienyl group,
substituents at the C5′ position should direct the isopropyl
featured simultaneous introduction of both asymmetric centers
and the multifunctionalized carbon chain, which made it possible
to establish short-step synthesis of polypropionates. Easy
preparation and stability of crystalline 1a and 1b make them to
be friendly compounds. Therefore, this methodology has been
used to natural product synthesis.4 Additionally, we have devel-
oped analogous reactions using 1b to synthesize a variety types of
polypropionates.5 In the report in 2004, we also revealed that
α-methyl-missing dienolate 3 possessed the diene chain in which
the reaction site directed far from the chiral auxiliary and thereby
the stereoselectivity reduced to be moderate (Scheme 1, eq 2).3a
Additionally, dienol ether 3 was found to be unstable for
purification by column chromatography, and the lability of 3
made the reaction to afford products 4 in low yield. Improvement
Received: November 22, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b03476
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Organic Letters
Letter
Table 1. Effect of Lewis Acid in the Vinylogous Mukaiyama
Aldol Reaction Using 5
a
entry
Lewis acid
yield (%)
dr (7:8)
Figure 2. Design of a new vinylketene silyl N,O-acetal.
1
2
3
4
TiCl4
85
76
27
88
85
80
1:7
1:7
BF3·OEt2
TMSOTf
SnCl4
group to cover the diene. Therefore, we decided to employ the
SuperQuat auxiliary having dimethyl6 or diphenyl groups7 at the
C5′ position of the oxazolidone ring. Additionally, TBDPS
instead of TBS would make the vinylketene silyl N,O-acetal more
stable.8
A new vinylketene silyl N,O-acetal 5 possessing 5′,5′-
diphenyloxazolidone and a tert-butyldiphenylsilyl group was
obtained as a single isomer by O-silylation of imide 67b (Scheme 2).
Dienol ether 5 was obtained as a crystal that allowed X-ray
crystallography (Figure 3). The crystal structure of 5 revealed
1:8
>20:1
10:1
10:1
b
5
SnCl4
c
6
SnCl4
a
PhCHO (1.05 equiv) and Lewis acid (1,0 equiv) were used.
5′-Nonsubstituted oxazolidone derivative was used. 5′,5′-Dimethy-
loxazolidone derivative was used.
b
c
in comparable yield and selectivity (entry 2), while TMSOTf
gave the product in low yield (entry 3). The best yield and
stereoselectivity were obtained by using SnCl4 (entry 4). In this
reaction, the predominant product was 5R-isomer 7, the isomer
possessing the opposite configuration at C5 position to 8. Use of
the 5′-nonsubstituted derivative of 5 and 5′,5′-dimethyl
derivative reduced both yield and stereoselectivity (entries 5
and 6).8 Therefore, we employed 5′,5′-diphenyloxazolidone
derivative 5 for further studies.
Scheme 2. Preparation of Vinylketene Silyl N,O-Acetal 5
Next, we examined the reaction with various aldehydes in the
presence of SnCl4 (Table 2). p-Bromo- and p-methoxybenzalde-
Table 2. Vinylogous Mukaiyama Aldol Reaction Using 5
entry
RCHO
PhCHO (a)
time (h) yield (%) dr (7:8)
1
2
3
4
5
6
7
8
9
3
3
88
93
95
27
66
72
65
88
76
86
>20:1
>20:1
20:1
10:1
15:1
>20:1
19:1
9:1
4-BrC6H4CHO (b)
4-MeOC6H4CHO (c)
4-NO2C6H4CHO (d)
EtCHO (e)
3
12
5
Figure 3. (A) ORTEP drawing of 5: front view. (B) ORTEP drawing
of 5: side view.
i-PrCHO (f)
8
c-HexCHO (g)
5
(E)-MeCHCHCHO (h)
(E)-MeCHCMeCHO (i)
(E)-MeCHCMeCHO (i)
14.5
20
4
that one of the phenyl groups on the oxazolidone ring deter-
mined the direction of the isopropyl group and another phenyl
group pushed the TBDPS group down. Therefore, one of the
phenyl groups of TBDPS was directed below the diene chain.
The isopropyl group on oxazolidone placed far from the terminal
carbon of the diene, the reaction site with an electrophile. This
conformation would be possible in a solution since NOE
correlation between H4′ and the tert-butyl group of TBDPS was
observed in CDCl3 (Scheme 2).
With vinylketene silyl N,O-acetal 5 in hand, the vinylogous
Mukaiyama aldol reaction with benzaldehyde using various
Lewis acid has been performed (Table 1). TiCl4 afforded
5S-isomer 8 as a major product in good yield and stereoselectivity
(Table 1, entry 1). Compared with dienol ether 3 (Table 1, eq 2),
both yield and stereoselectivity were improved, which reflected
reform of the chiral vinylketene silyl N,O-acetal. The products
attached the TBDPS group; thus, protected aldol adducts were
obtained in one step.9 BF3·OEt2 afforded the same major product
5:1
a
10
1:20
a
BF3•OEt2 was used as Lewis acid.
hyde also gave the O-protected adduct in high yield with
excellent selectivity (Table 2, entries 2 and 3). In the case of
p-nitrobenzaldehyde (entry 4), the reaction proceeded slowly and
afforded O-protected adduct in low yield but good selectivity.
Products possessing free hydroxy groups were obtained as a
mixture of diastereomers. Saturated alkylaldehydes including
linear and branched side chains gave O-protected adducts in
good yield with high stereoselectivity (entries 5−7). In the case
of α,β-unsaturated aldehydes (entries 8 and 9), the reaction
gave O-protected adduct in good yield with good to moderate
selectivity. When a mixture of dienol ether 5 and tiglic aldehyde
was treated with BF3·OEt2, the stereoselectivity was switched and
B
DOI: 10.1021/acs.orglett.6b03476
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Letter
the 5S-isomer 8 was obtained in high yield with excellent
stereoselectivity (entry 10).
Table 3. Comparison of Oxazolidones for the Vinylogous
Mukaiyama Aldol Reaction
Interested in the stereoselectivity switching by using SnCl4, we
examined a control experiment without aldehyde. Treatment of
vinylketene silyl N,O-acetal 5 with SnCl4 in dichloromethane at
−78 °C smoothly afforded a mixture of geometric isomers in
which the E-isomer 9 existed as the major isomer.10 Toluene gave
the mixture in quantitative yield with comparable stereo-
selectivity. The resulting mixture of vinylketene silyl N,O-acetal
5 and 9 was submitted to the reaction with benzaldehyde and
SnCl4 under the same conditions, which gave the same results as
entry 4 in Table 1. On the other hand, treatment of the mixture of
5 and 9 with benzaldehyde in the presence of BF3·OEt2 gave 7 as
a major product. Since BF3·OEt2 did not promote isomerization
of vinylketene silyl N,O-acetal 5, the major product of the
reaction was derived from E-isomer 9 in Scheme 3.
a
entry
R
R′
yield (%)
dr (13/isomers )
b
1
Me (10m)
Ph (10p)
Me (10m)
Ph (10p)
4-BrC6H4
4-BrC6H4
Et
78
61
72
19:1
15:1
12:1
4:1
b
2
c
3
b
4
Et
47
a
b
Three diastereomers were included. Determined by 400 MHz
c
1H NMR. Determined by HPLC.
The vinylogous Mukaiyama aldol reaction using 10m
was performed with various aldehydes (Table 4).12 Aromatic
Scheme 3. Isomerization of 5 and the Vinylogous Mukaiyama
Aldol Reaction Using the Geometric Mixture
Table 4. Vinylogous Mukaiyama Aldol Reaction Using 10m
a
entry
RCHO
PhCHO (a)
yield (%)
dr (11/isomers )
b
1
2
3
4
5
6
7
66
78
68
71
73
62
16:1
b
4-BrC6H4CHO (b)
4-NO2C6H4CHO (c)
EtCHO (d)
19:1
b
14:1
c
12:1
c
i-PrCHO (e)
6:1
c
c-HexCHO (f)
5:1
d
(E)-MeCHCMeCHO (g)
0
When the reaction proceeded with BF3·OEt2 in only 1 min,
E-enolate 9 disappeared, while Z-enolate 5 remained in the
reaction mixture (Scheme 4). The adduct 7 was obtained with
a
b
Three diastereomers were included. Determined by 400 MHz
c
d
1H NMR. Determined by HPLC. Michael adducts were obtained as
a diastereomeric mixture.
Scheme 4. Reactivity of E- and Z-Enolates
compounds including benzaldehyde, p-bromobenzaldehyde, and
p-nitrobenzaldehyde gave O-silylated anti adduct 11 in good
yield with high stereoselectivity (Table 4, entries 1−3).
Propionaldehyde gave TBDPS-protected adduct 11 in high
selectivity, while branched saturated aldehyde including
isobutyraldehyde and cyclohexanecarboxaldehyde gave anti
adduct in good to moderate selectivity (entries 4−6). However,
tiglic aldehyde, an α,β-unsaturated aldehyde, promoted the con-
jugate addition to give Michael adducts as a diastereomeric
mixture and did not afford aldol adduct (entry 7).
These results, including X-ray crystallography of vinylketene
silyl N,O-acetal 5, Sn(IV)-mediated geometry-shuffling, and the
vinylogous Mukaiyama aldol reactions, suggest reaction
mechanisms shown in Scheme 5. X-ray crystallography of 5
indicated that one of the phenyl groups of TBDPS covered the
lower face of the diene. Therefore, an electrophile should
approach from the upper face. Additionally, aldehyde was placed
to avoid steric repulsion of H2 in the preferred transition state.
These factors might lead to the stereocontrol modes shown in
Scheme 5. In the case of using TiCl4 and BF3·OEt2, the reaction
proceeded via the transition state 12 to give adduct 8 as a major
product (Scheme 5, route A). On the other hand, SnCl4 isom-
erized 5 to more reactive diene 9, which also allowed the
electrophilic attack from the upper face. This face selectivity
was proved by using methyl-attaching diene 10, which gave
high stereoselectivity (dr 15:1), which indicated that E-enolate 9
was more reactive than Z-enolate 5 and was converted to 7 in
high stereoselectivity.
Next, we examined the vinylogous Mukaiyama aldol reaction
by using vinylketene silyl N,O-acetal 10 possessing the terminal
methyl group (Table 3). 5′,5′-Dimethyloxazolidone derivative
10m and 5′,5′-diphenyloxazolidone derivative 10p were
compared in yield and stereoselectivity of the reaction. Addition
of Cu(II) triflate improved the reproducibility of the reaction.11
5′,5′-Dimethyloxazolidone derivative 10m provided anti adduct
11 in good yield and excellent stereoselectivity (Table 3, entry 1).
5′,5′-Diphenyloxazolidone derivative 10p also gave 11 in
reduced yield and stereoselectivity (entry 2). The difference in
these derivatives was found clearly in the reactivity for
propionaldehyde (entries 3 and 4). Although 10m retained
good yield and stereoselectivity (entry 3), 10p gave moderate
yield and selectivity (entry 4). Therefore, 5′,5′-dimethyloxazo-
lidone derivative 10m was preferred over diphenyl deriva-
tive 10p.
C
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4R-adduct 11 (Tables 3 and 4). Therefore, the transition state of
this reaction might be drawn as 13 (Scheme 5, route B). TBDPS
migrated to prepare the stable TBDPS-O bond with an aldol
adduct.
In conclusion, remote asymmetric induction reactions using
crotonate-derived vinylketene silyl N,O-acetal have been
developed. SnCl4 was found to isomerize the geometry of the
silyl dienol ether, and the resulting E-enolate 9 showed high
reactivity to give the adduct with high stereoselectivity.
Aldehydes approached from the upper face of 5 and 9, while
previous reactions in Scheme 1 proceeded from the lower face of
1a and 1b. These results indicated a new system of remote
asymmetric induction. Vinylketene silyl N,O-acetal 10m gave
anti adducts in good to high stereoselectivity and indicated
the face selectivity of dienolates. These reactions would be
straightforward methods to synthesize polyketides.
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Org. Lett. 2014, 16, 4106. (d) Nakamura, T.; Kubota, K.; Ieki, T.;
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b03476.
(6) (a) Davies, S. G.; Sanganee, H. J. Tetrahedron: Asymmetry 1995, 6,
671. (b) Bull, S. G.; Davies, S. G.; Jones, S.; Polywka, M. E. C.; Prasad, R.
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(8) Relation of stability and stereoselectivity of vinylketene silyl
N,O-acetal was revealed in the catalytic enantioselective vinylogous
Mukaiyama aldol reaction: Denmark, S. E.; Heemstra, J. R., Jr. J. Org.
Chem. 2007, 72, 5668.
X-ray data for compound 1a (CIF)
X-ray data for compound 5 (CIF)
Experimental procedures, optimization of the reactions
with 5 and 10m, spectral data of compounds, and 1H and
13C NMR spectra (PDF)
X-ray data for compound S5 (CIF)
(9) (a) Saigo, K.; Osaki, M.; Mukaiyama, T. Chem. Lett. 1975, 4, 989.
(b) Carreira, E. M.; Singer, R. A. Tetrahedron Lett. 1994, 35, 4323.
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reported, the transformation of silyl enol ether to α-stannylketone was
revealed: (a) Nakamura, E.; Kuwajima, I. Chem. Lett. 1983, 12, 59.
(b) Gennari, C.; Bernardi, A.; Poli, G.; Scolastico, C. Tetrahedron Lett.
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: seijiro@waseda.jp.
ORCID
Seijiro Hosokawa: 0000-0002-8036-532X
Notes
The authors declare no competing financial interest.
(11) (a) Kruger, J.; Carreira, E. M. J. Am. Chem. Soc. 1998, 120, 837.
̈
(b) Bluet, G.; Bazan
3807. (c) Moreau, X.; Bazan
Soc. 2005, 127, 7288. (d) Bazan
Campagne, J.-M. Chem. - Eur. J. 2006, 12, 8358. Cu enolate as the
́
-Tejeda, B.; Campagne, J.-M. Org. Lett. 2001, 3,
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ACKNOWLEDGMENTS
́
■
́
We are grateful for financial support from The Kurata Memorial
Hitachi Science and Technology Foundation and The Naito
Foundation.
intermediate was revealed: Pagenkopf, B. L.; Kruger, J.; Stojanovic, A.;
̈
Carreira, E. M. Angew. Chem., Int. Ed. 1998, 37, 3124.
(12) For the case of TiCl4 and BF3·OEt2 employed as the Lewis acid,
see the Supporting Information.
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