Catalytic enantioselective silylation of N-sulfonylimines: Asymmetric synthesis of α-amino acids from CO2 via stereospecific carboxylation of α-amino silanes

Article abstract of DOI:10.1021/ol501143c

A catalytic enantioselective silylation of N-tert-butylsulfonylimines using a Cu-secondary diamine complex was demonstrated. The resulting optically active α-amino silanes could be carboxylated under a CO₂ atmosphere (1 atm) to afford the corresponding α-amino acids in a stereoretentive manner. This two-step sequence provides a new synthetic protocol for optically active α-amino acids from gaseous CO₂ and imines in the presence of a catalytic amount of a chiral source.

Full text of DOI:10.1021/ol501143c

Letter
pubs.acs.org/OrgLett
Catalytic Enantioselective Silylation of N‑Sulfonylimines: Asymmetric
Synthesis of α‑Amino Acids from CO2 via Stereospecific
Carboxylation of α‑Amino Silanes
Tsuyoshi Mita,*,† Masumi Sugawara,† Keisuke Saito,† and Yoshihiro Sato*,†,‡
†Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
‡ACT-C, Japan Science and Technology Agency (JST), Sapporo 060-0812, Japan
S
* Supporting Information
ABSTRACT: A catalytic enantioselective silylation of N-tert-
butylsulfonylimines using a Cu−secondary diamine complex
was demonstrated. The resulting optically active α-amino silanes
could be carboxylated under a CO2 atmosphere (1 atm) to
afford the corresponding α-amino acids in a stereoretentive
manner. This two-step sequence provides a new synthetic protocol for optically active α-amino acids from gaseous CO2 and
imines in the presence of a catalytic amount of a chiral source.
atalytic enantioselective silylation has received much
attention over the past decade due to the versatility of
amido stannanes11 derived from Ellman’s chiral tert-butylsulfi-
namide undergo stereospecific carboxylation with CO2 using
CsF to afford optically active α-amino acid derivatives.12 In
contrast, when optically active N-Boc-α-amido stannanes and
silanes were utilized as substrates for carboxylation, their optical
purity was lost and only racemic products were obtained.12−14
On the basis of these findings, we considered that N-tert-
butylsulfonyl-α-amido silanes would also be carboxylated in a
stereospecific manner even under milder conditions because a
Si atom is more prone to activation by fluoride than a Sn atom
(bond dissociation energy: 565 kJ/mol for Si−F and 414 kJ/
mol for Sn−F).15
First, we engaged in the development of a catalytic
enantioselective silylation of N-tert-butylsulfonylimine 1a.
Substantial screening for the combination of a Rh/Cu salt
and a chiral phosphine ligand with PhMe2Si-Bpin led to
unsatisfying yields and ee’s. We next considered employing
chiral amine ligands. In 2010, Shibasaki, Kanai, and co-workers
reported enantioselective 1,4-borylation using a Cu−secondary
diamine L-b complex,16 which actually worked very well for 1,2-
silylation of imines 1a. The reaction of 1a with PhMe2Si-Bpin
(1.2 equiv) in the presence of CuOTf·1/2C6H6 (10 mol %), L-
b (20 mol %), and i-PrOH (2 equiv) proceeded smoothly in
DME at 30 °C to afford the optically active α-amino silane 2a
in 93% yield with 83% ee (Table 1, entry 2).
C
the resultant optically active silylated compounds. Therefore,
several methods have been devised using chiral Rh,1a−c Cu,1d−j
and Pd2 complexes. Reactive bismetals such as PhMe2Si-Bpin1,3
2
and PhCl2Si-SiMe3 were usually employed as silylating
reagents for these silylations. Although there are many reports
on enantioselective 1,4-silylations of α,β-unsaturated carbonyl
compounds, examples of 1,2-silylations have been very
limited.1g,4 In 2011 Oestreich et al. reported Cu-catalyzed
silylation of imines (racemic version),4a and in 2013 Riant et al.
developed enantioselective silylation of aldehydes using a Cu−
phosphine complex.1g However, there had been no report of
enantioselective 1,2-silylation of imines until early 2014.4b We
herein disclose a new entry of catalytic enantioselective
silylation of N-tert-butylsulfonylimines using a Cu−secondary
diamine complex.
As a further benefit, the resulting optically active α-amino
silanes are expected to be transformed into the corresponding
α-amino acids by stereospecific carboxylation with CO2 by a
fluoride under mild conditions.5 It is well-known that optically
active α-amino acids are primal units of proteins and peptides,
and they are frequently utilized as chiral building blocks for
asymmetric synthesis of natural products and catalysts.6 Thus,
this synthetic strategy is of great importance not only for the
utilization of CO2, an abundant, inexpensive, and relatively
nontoxic C1 source,7 but also for providing a new and
alternative method for the synthesis of optically active α-amino
acid derivatives via carboxylation of amine derivatives. There
are several methods for preparing chiral α-amino acid
derivatives via both chemical6 and biochemical processes,8
among which the utilization of CO2 is limited and mostly
represented by enantioselective α-carboxylation of α-amino
stannanes9 or alkyl amines10 using a combination of BuLi and
an appropriate chiral amine such as (−)-sparteine. Our group
already revealed that optically active N-tert-butylsulfonyl-α-
Encouraged by the good performance of the Cu−secondary
diamine complex, we screened the structures of ligands (Table
1). When the desired silylation was slow, 1a was somewhat
decomposed to produce sulfonamide 3 and benzaldehyde (4a)
in addition to the recovery of 1a. Examination of alkyl
substituents (R1) of 1,2-diphenylethylenediamine showed that
the ethyl substitution exhibited the best performance (entries
Received: April 20, 2014
© XXXX American Chemical Society
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Letter
silylation with higher ee’s. Not only aliphatic alcohols (entries
2−5) but also phenol derivatives were effective as proton
sources (entries 6−8). In response to the steric bulk of an
alcohol, the enantioselectivity of the product increased.
However, much bulkiness impeded both the enantioselectivity
and yield (entry 8). On the basis of these observations, 2,6-
xylenol was the most suitable additive for this 1,2-silylation of
imines (91% yield, 86% ee) (entry 7).
Table 1. Screening of Diamine Ligands
With the optimal conditions in hand, the substrate scope was
examined (Table 3). Silylations of imines bearing an electron-
Table 3. Substrate Scope
a
b
1
Isolated yield. Yields were determined by H NMR analysis using
c
1,1,2,2-tetrachloroethane as an internal standard. Ee’s were
determined by HPLC analysis.
1−3). The electronic effects on the arene part of the ligand
were then investigated. When ligands bearing an electron-rich
arene were employed, ee’s slightly dropped (entries 4 and 5).
On the other hand, the substitution of an electron-deficient
arene resulted in decreases in both yields and ee’s (entries 6−
8). Based on these results, L-b was selected as a suitable ligand
for further investigation.
Next, we examined additive effects (Table 2). Most of the
Rh/Cu-catalyzed 1,2- or 1,4-silylations to carbonyl compounds
required a proton source such as an alcohol to accelerate the
catalyst regeneration step.1 Without an alcohol, the reaction
was sluggish and 2a was obtained only in 42% yield with 68%
ee (entry 1). The addition of an alcohol accelerated the
a
b
c
Isolated yields. Ee’s were determined by HPLC analysis. Reaction
d
time was 3 h. Reaction was conducted at 0 °C for 13 h.
Table 2. Screening of Proton Sources
withdrawing group on the aromatic ring gave slightly lower
yields and ee’s (entries 2 to 4). In contrast, substitutions of an
electron-donating group on the aromatic ring led to higher
yields and ee’s (entries 5 to 10). The product was obtained with
95% ee when the methyl group was substituted at the ortho-
position (entry 9). In addition, silylations of the substrates
possessing 2-thiophene and 2-naphthalene proceeded with high
yields and ee’s (entries 11 and 12). α-Alkenyl imines were also
applicable in this 1,2-silylation without the generation of 1,4-
silylated compounds (entries 13 and 14). α-Amino silane
bearing an α-alkyl group was also obtained by this method,
albeit in low yield (entry 15).
This enantioselective silylation could be performed on a
gram scale (1.5 g) without any difficulties (Scheme 1). After
recrystallization twice, optically pure α-amino silane 2a was
obtained in 52% yield. The absolute configuration of 2a was
determined as R by X-ray crystallographic analysis of this
enantiopure crystal (Figure 1).17
Having established an efficient silylation of N-tert-butylsulfo-
nylimines to obtain enantioenriched α-amino silanes, we next
evaluated the stereospecificity of CsF-mediated carboxylation
with CO2 (balloon) (Table 4). Optically active α-amino silanes
shown in Table 4 were prepared either by this silylation or
diastereoselective silylation of (R)-tert-butylsulfinylimine with
a
b
1
Isolated yield. Yields were determined by H NMR analysis using
c
1,1,2,2-tetrachloroethane as an internal standard. Ee’s were
determined by HPLC analysis.
B
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Letter
in a higher level of stereospecificity, selectively producing 5a in
85% ee without the generation of 6a (entry 3). Moreover,
substrates bearing both electron-donating and -withdrawing
substituents underwent carboxylations smoothly to afford 5 in
high yields with high ee’s (entries 4−6). However, α-alkyl
substrate 2o was not tolerable in this carboxylation even at 100
°C and only the protodesilylation product 6o was selectively
produced (entry 7). The use of α-alkenyl α-amino silane 2p did
not promote the desired carboxylation well, but the target
amino acid was obtained with high stereospecificity (entry 8).
An increase of CO2 pressure (10 atm) improved the yield with
the ee being maintained (entry 9).
Scheme 1. Gram-Scale Synthesis of α-Amino Silane
The absolute configuration of 5a was determined as S by
comparison of the optical rotation value with the reported
one.18 This assignment indicated that the carboxylation of N-
tert-butylsulfonyl-α-amido silanes proceeded in a stereo-
retentive manner.19
In summary, we successfully developed the asymmetric
synthesis of α-amino silanes by a Cu-catalyzed enantioselective
silylation of N-tert-butylsulfonylimines. N-tert-Butylsulfonyl-α-
amido silanes thus obtained were converted into optically active
α-amino acid derivatives via stereoretentive carboxylation under
1 atm of CO2 atmosphere. Combined with the silylation and
carboxylation, we eventually succeeded in the development of
the asymmetric synthesis of α-amino acids using CO2.
Examination of a broader substrate scope including ketoimines
to prepare quaternary α-amino acids is in progress.
Figure 1. ORTEP figure of α-amino silane 2a (Flack parameter is
0.00(3).).
Table 4. Stereospecific Carboxylations of α-Amino Silanes
ASSOCIATED CONTENT
* Supporting Information
■
S
Details of experimental procedures and physical properties of
new compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: tmita@pharm.hokudai.ac.jp.
*E-mail: biyo@pharm.hokudai.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Dr. Takashi Matsumoto in Rigaku Corporation is greatly
acknowledged for X-ray crystallographic analysis. This work
was financially supported by Grants-in-Aid for Young Scientists
(B) (No. 24750081) and for Scientific Research (B) (Nos.
23390001, 26293001) from JSPS and by a Grant-in-Aid for
Scientific Research on Innovative Areas “Molecular Activation
Directed toward Straightforward Synthesis (No. 25105701)”
from MEXT. M.S. thanks JSPS for a fellowship (No.
25002099).
a
b
1
Isolated yield. Yields were determined by H NMR analysis using
c
1,3,5-trimethoxybenzene as an internal standard. Ee’s were
determined by HPLC analysis. Triglyme was used as a solvent. 10
atm of CO2.
d
e
LiSiMe2Ph4c followed by oxidation. Our previous study on
carboxylation of N-tert-butylsulfonyl-α-amido stannanes dem-
onstrated that triglyme (triethylene glycol dimethyl ether) was
a suitable solvent for stereospecific carboxylation at a high
temperature (100 °C).12 However, in the case of α-amino
silanes, carboxylation proceeded similarly in both triglyme and
DMF even at rt (entries 1 and 2). By using DMF as a solvent,
amino acid 5a was obtained in 57% yield with 52% ee after
methyl esterification with TMSCHN2, together with a small
amount of protodesilylation byproduct 6a (entry 2).
Furthermore, a decrease in temperature to −20 °C resulted
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