A versatile approach to noncoded β-hydroxy-α-amino esters and α-amino acids/esters from morita-baylis-hillman adducts

Article abstract of DOI:10.1055/s-0034-1379168

A simple and straightforward approach to the diastereoselective synthesis of noncoded β-hydroxy-α-amino esters from Morita-Baylis-Hillman (MBH) adducts is described. The strategy is based on a one-pot sequence involving an oxidative cleavage of the double bond of silylated Morita-Baylis-Hillman adducts, followed by the reaction with hydroxylamine hydrochloride/pyridine to form oximes. The stereoselective reduction of the oximes with the mixture MoCl₅·nH₂O/NaBH₃CN led to the corresponding anti-β-hydroxy-α-amino esters in four steps in good overall yield and with diastereoselectivity higher than 95%. A slight modification of the synthetic approach has allowed for the racemic synthesis of a set of noncoded α-amino esters/acids and DOPA

Full text of DOI:10.1055/s-0034-1379168

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 0113–0123
paper
113
H. Ullah et al.
Paper
Synthesis
A Versatile Approach to Noncoded β-Hydroxy-α-amino Esters and
α-Amino Acids/Esters from Morita–Baylis–Hillman Adducts
Noncoded Amino Acids from Morita–Baylis–Hillman Chemistry
Hamid Ullaha
André V. Ferreiraa,b
José A. Bendassollib
Manoel T. Rodrigues, Jr.a
André Luiz B. Formigac
Fernando Coelho*a
OH
OTBS
high
CO2R2
CO2R2
4 steps
R1
CO2R2
3 steps
diastereoselectivity
R1
R1
NH2
NH2
( )-α-amino esters
R1 = alkyl, aryl
2 = Me, Et
good overall yield
anti; dr 95:5
O-silylated β-hydroxy-
α-amino esters
or acids
R
a University of Campinas, Institute of Chemistry, Laboratory of
Synthesis of Natural Products and Drugs, P. O. Box 6154,
13083-970 Campinas, SP, Brazil
coelho@iqm.unicamp.br
b Center for Nuclear Energy, University of São Paulo –
CENA/USP, Stable Isotopes Laboratory, P. O. Box 96,
13400-970 Piracicaba, SP, Brazil
c University of Campinas, Institute of Chemistry, Laboratory of
Coordination Chemistry, P. O. Box 6154, 13083-970
Campinas, SP, Brazil
+
5
5
1
(
9
3
)
7
8
8
3
0
2
3
Received: 09.07.2014
Accepted after revision: 26.08.2014
Published online: 02.10.2014
O
Cl
H2N
CO2H
OH
CO2H
HN
HO
DOI: 10.1055/s-0034-1379168; Art ID: ss-2014-m0435-op
O
N
H
CO2H
Cl
H
Abstract A simple and straightforward approach to the diastereose-
lective synthesis of noncoded β-hydroxy-α-amino esters from Morita–
Baylis–Hillman (MBH) adducts is described. The strategy is based on a
one-pot sequence involving an oxidative cleavage of the double bond of
silylated Morita–Baylis–Hillman adducts, followed by the reaction with
hydroxylamine hydrochloride/pyridine to form oximes. The stereoselec-
tive reduction of the oximes with the mixture MoCl5·nH2O/NaBH3CN
led to the corresponding anti-β-hydroxy-α-amino esters in four steps in
good overall yield and with diastereoselectivity higher than 95%. A
slight modification of the synthetic approach has allowed for the race-
mic synthesis of a set of noncoded α-amino esters/acids and DOPA.
SO2NH2
HN
H
Me
CO2H
OH
kaitocephalin (1)
N
H
O
H2N
altemicidin (3)
OH OH
HO2C
H2N
OH
OH
O
Key words Morita–Baylis–Hillman adducts, amino acids, reduction,
diastereoselectivity, DOPA
sphingofungin E (2)
β-Hydroxy-α-amino acids/esters and their correspond-
ing vicinal amino alcohols are essential building blocks
found in a variety of pharmacologically active natural prod-
ucts, herbicides, and fungicides. This basic structural unit
can be found in proteins (through the amino acids serine
and threonine)1 and in several biologically active natural
products.2 In Figure 1, some representative examples of
natural products containing this unit are shown.
Kaitocephalin (1) is a pyrrolidine alkaloid, isolated from
the filamentous fungus Eupenicillium shearii PF1191.3 Due
to the suppression of kainic acid toxicity, this compound is
a candidate for use as a lead compound in the development
of new medicines for the treatment of neurological diseases
related to glutamate excitotoxicity.4 Sphingofungin E (2) is
also an example of a compound containing the β-hydroxy-
α-amino acid moiety. This compound has a potent immu-
nosuppressive activity.5 Altemicidin (3) is a six-azaindene
monoterpene alkaloid, which exhibits a strong acaricidal
activity along with a promising inhibition activity of tumor
N
O
H
O
N
HO
Me
N
O
O
H
N
O
O
N
O
Me
HO
HN
HN
H
N
O
MeO
cyclomarin A (4)
Figure 1 Some representative examples of biologically active natural
products containing the β-hydroxy-α-amino acid/ester unit
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 113–123

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H. Ullah et al.
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Synthesis
cell growth.6 The β-hydroxy-α-amino acid/ester unit can
also be presented as part of a cyclic compound. The family
of cyclomarins exemplifies this property. The most abun-
dant component of this family, cyclomarin A (4), exhibits
anticancer and anti-inflammatory activities both in vivo
and in vitro.7
OR2
OR2
OR2
CO2R3
CO2R3
OH
CO2R3
R1
R1
R1
NH2
N
R1 = aryl, alkyl
R2 = TBS
R3 = H, Me
silylated MBH adducts
α-oxyimino acids/esters
Noncoded amino acids/esters offer structural units with
extensive use in the design of new protease inhibitors and
in the determination of the specificity of proteases.8 More-
over, β-hydroxy-α-amino acids/esters can be readily trans-
formed into a variety of catalyst, ligands, chiral auxiliaries,
and other valuable compounds that may serve as useful
precursors in organic synthesis. For instance, β-hydroxy-α-
amino carbonyl compounds are more often employed as in-
termediates for the syntheses of compounds such as, 2-ami-
nopropane-1,3-diols9 (key intermediates to the synthesis of
oxazolidine-2-ones), lactams such as (+)-lactacystin (which
is a strong and selective inhibitor of the proteasome),10 par-
ent β-hydroxy-α-amino acids, β-halo-α-amino acids, and
aziridines.11,12
The essential role played by β-hydroxy-α-amino acid es-
ters in biological systems, as characterized by great syn-
thetic versatility, has attracted an interest on the part of the
synthetic community in preparing these building blocks,
especially in a stereoselective manner.13 As a consequence,
a number of useful enzymatic and chemical approaches for
their syntheses are available. Some of these methods are
the aldol reaction (including enzymatic versions),14 the
Strecker reaction,15 dihydroxylation reactions,16 aminohy-
droxylation,17 epoxidations,18 use of azomethine ylide,19 hy-
drogenation and dynamic kinetic resolution,20 oxy-Michael
additions,21 photocycloadditions,22 oxazolidinones,12a,23 sig-
matropic rearrangements,24 and the Ireland–Claisen rear-
rangement.25 These methods have appealing aspects, but
they also suffer from disadvantages such as low overall
yields, multiple synthetic steps, and in certain cases, expen-
sive and or drastic reaction conditions. Additionally, re-
markably few efforts to synthesize these target amino acids
or esters from β-hydroxy-α-oxyimino esters have been re-
ported to date.26 This motivated us to develop an alternative
approach to α-oxyimino esters from Morita–Baylis–
Hillman adducts. The stereoselective reduction of these in-
termediates would allow for fast and easy access to β-hy-
droxy-α-amino esters and noncoded amino acids.
β-hydroxy-α-amino acids/esters
Scheme 1 Retrosynthetic analysis for the preparation of β-hydroxy-α-
amino acid/esters
We describe herein a fast, simple, and alternative ap-
proach to the synthesis of β-hydroxy-α-amino esters,
which is based on the stereoselective reduction of oxyimi-
noesters that are easily obtained from Morita–Baylis–
Hillman adducts. The same approach also allowed for de-
scribing the synthesis of noncoded amino acids.
We began this work by preparing some Morita–Baylis–
Hillman (MBH) adducts, using a method that was previous-
ly described by our group.28 Specifically, a mixture of a suit-
able aldehyde with methyl acrylate and DABCO was soni-
cated for a few hours to yield the corresponding MBH ad-
ducts in good to excellent yields (Table 1).
Table 1 Preparation of the MBH Adductsa
OH
O
a
CO2Me
R
R
H
R = aryl, alkyl
MBH adducts 5–15
MBH adduct
Yield (%)b
Entry
R
1
6-bromopiperonyl
4-MeOC6H4
4-t-BuC6H4
Ph
5
82
76
78
87
80
82
93
88
75
70
70c
2
6
3
7
4
8
5
Et
9
6
3-ClC6H4
10
11
12
13
14
15
7
4-O2NC6H4
4-ClC6H4
8
9
4-BrC6H4
10
11
3,4,5-(MeO)3C6H2
piperonyl
The designed strategy is based on a one-pot synthesis of
oxyimino esters through ozonolysis and oximation of si-
lylated (TBS)-protected Morita–Baylis–Hillman (MBH) ad-
ducts. The diastereoselective reduction of oxyimino deriva-
tives forms the desired amino acid esters, as illustrated in
the retrosynthetic analysis depicted below (Scheme 1).
Based on our previous results and those of others,27 a good
control of the relative stereochemistry during the reduction
step was expected.
a Reaction conditions: a) methyl acrylate (excess), DABCO, ultrasound, r.t.,
3–144 h.
b Yields refer to isolated and purified products.
c In this particular case, the reaction was carried out in the presence of 2–3
drops of [bmim]Br.
Next, a subset of these MBH adducts 5–11 was treated
with tert-butyldimethylsilyl chloride in the presence of im-
idazole and anhydrous DMF (few drops when necessary) to
give the corresponding silylated adducts in excellent yields
in a few hours (Table 2).
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Table 2 Silylation of MBH Adducts and Preparation of the Oxyimino
Recently, Kouhkan et al.31 reported on a mild and simple
method to reduce an oxime directly to an amine. This meth-
od is based on the combination of a reducing agent with a
molybdenum salt and a buffer to generate the amine in
good yields.
Estersa
OTBS
OTBS
OH
CO2Me
OH
a
b
CO2Me
CO2Me
R
R
R
Thus, an ethanolic solution of the corresponding oxy-
N
imino esters 23–29 was added to
a
mixture of
MBH adducts
5–11
16–22
23–29
NaBH3CN/MoCl5/NaHSO4·H2O to generate the amino esters
in good to excellent yields. In a careful analysis of the NMR
spectra of the crude products, the presence of a mixture of
diastereoisomers was not observed. In most cases, only one
isomer was observed, which demonstrates the high level of
diastereoselection attained in this reduction step.32 The
only exception occurred with oxyimino ester 27 (Table 3,
entry 5). In this particular instance, one of the substituents
was a small alkyl group, which is a possible reason for the
observed decrease in the level of diastereoselection (Table
3).
Entry
MBH adduct, R
Silylated MBH,
yield (%)
Oxyimino ester,
yield (%)b
1
2
3
4
5
6
7
5, 6-bromopiperonyl
6, 4-MeOC6H4
7, 4-t-BuC6H4
8, Ph
16, 92
17, 91
18, 90
19, 93
20, 85
21, 94
22, 92
23, 89
24, 91
25, >98
26, 94
27, 90
28, 96
29, 80
9, Et
10, 3-ClC6H4
11, 4-O2NC6H4
a Reaction conditions: a) TBSCl, imidazole, DMF, r.t., 4–6 h; b) i. O3, MeOH,
–78 °C, 15–30 min, ii. Me2S, –78 °C to r.t., 1 h, iii. MeOH, NH2OH·HCl, pyri-
dine, reflux, 50 min.
Table 3 Synthesis of O-Silylated β-Hydroxy-α-amino Esters from Oxy-
imino Estersa
b Yields refer to isolated and purified products. However, after isolation, the
crude compounds exhibited a high degree of purity and no chromato-
graphic purification proved to be necessary.
OTBS
OTBS
OTBS
N
+
CO2Me
a
CO2Me
CO2Me
OH
R
R
R
NH2
syn
NH2
anti
The TBS protection step is necessary for two reasons:
the ozonolysis reaction of the silylated MBH adducts is
more efficient and clean, and the product can be easily pu-
rified, if necessary. The bulky nature of this protecting
group is the second reason that justifies its use. In previous
work, we have demonstrated the influence of this protect-
ing group in the diastereoselectivity of some reactions, such
as heterogeneous hydrogenation and epoxidation.27
Ozonolysis of the silylated MBH adducts at –78 °C gave,
after 15–50 minutes, the corresponding α-keto-β-silyloxy
esters, which, in turn, were initially treated with dimethyl
sulfide at the same temperature.29 Next, hydroxylamine hy-
drochloride and pyridine (1 equiv each) were added to the
reaction medium, and the temperature was raised to 60 °C
to give the oxyimino esters 23–29, in good to excellent
yields after one hour (Table 2). The tiny amount of DMSO
formed in the reaction after the ozonide’s reductive workup
probably accelerates the reaction by providing more polar
organic media.
For all synthesized oximes, the formation of a mixture
of isomers was observed. No efforts were made to deter-
mine the configuration of the major isomer in this step.
To complete this sequence, the oximes have to be re-
duced to the corresponding amino groups. Several methods
are available to carry out this transformation selectively.30
However, we were interested in using mild conditions to
avoid the removal of the acid-sensitive protecting group.
oxyimino esters
O-silylated β-hydroxy-α-amino esters
30–36
23–29
Entry
R
Product, yield (%)b
drc
>95:5
1
2
3
4
5
6
7
23, 6-bromopiperonyl
24, 4-MeOC6H4
25, 4-t-BuC6H4
26, Ph
30, 88
31, 95
32, 93
33, 93
34, 91
35, 96
36, 80
>95: 5
>95:5
>95: 5
78:22
>95: 5
>95:5
27, Et
28, 3-ClC6H4
29, 4-O2NC6H4
a Reaction conditions: a) MoCl5, NaBH3CN, NaHSO4·H2O, EtOH, reflux.
b Yields refer to isolated and purified compounds.
c The diastereoselectivity was determined by analysis of the 1H NMR spec-
trum of the crude reaction mixture.
Seeking to determine unambiguously the relative ste-
reochemistry of amino esters, one of the silylated amino es-
ters was converted into a known compound. Amino ester
33 (Table 3) was therefore treated with TBAF in THF for 45
minutes to give methyl β-phenylserinate (37), in 92% yield.
Both diastereoisomers (anti and syn) of this noncoded ami-
no ester are well known, and the complete set of spectral
data is available in the literature (Scheme 2).33
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H. Ullah et al.
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Synthesis
OH
coordination through the nitrogen atom converged to the
oxygen bound complexes. Apparently, the five membered
ring in these cases resulted in unstable coordination modes
due to steric hindrance.
OTBS
CO2Me
NH2
a
CO2Me
NH2
33
The most stable complex can be seen in Figure 2 (geo-
metric parameters of the complex can be found as Support-
ing Information together with the most stable structure ob-
tained for 26). Coordination of the [MoCl4]+ fragment re-
stricts rotation of OTBS around the C–O bond forcing the
bulk group to be positioned over the carbon that will be at-
tacked by the hydride. Even if the rotation around the O–Si
bond is not completely restricted in the complex, coordina-
tion imposes a serious steric hindrance effect for reduction
in only one side.
Analysis of the free molecule 26 reveals that the effect is
indeed important since when the metal fragment is re-
moved, the bulky group settles away from the reaction site,
that is, without coordination, the OTBS group is no longer
selecting the preferred site for hydride attack.
Comparison with ligand 26 structure shows that coordi-
nation increases the N–OH bond distance of the oxime
group by 0.06 Å and decreases the C(sp2)–N bond by 0.01 Å
revealing that coordination has a role in weakening the N–
OH bond.
The observed selectivity can be inferred from the for-
mation of a transition state in which the hydride approach
occurs only from the less-hindered side, yielding a product
with relative anti-stereochemistry.
37
Scheme 2 Synthesis of the anti methyl β-phenylserinate (37). Reagents
and conditions: a) TBAF, THF, 45 min, 0 °C, 92%.
1
The analysis of the H NMR spectrum of compound 37,
which was synthesized using our sequence, shows a dou-
blet centred at 4.9 ppm with a coupling constant (J) of 6.0
Hz, and a second doublet centred at 3.56 ppm with the
same value of coupling constant. These data were then
compared with those available in the literature for the same
compound.
The data for the known anti-diastereoisomer show the
carbinolic hydrogen (CHOTBS) as a doublet, centred at 4.9
ppm, with a coupling constant of 5.5 Hz, while for the
known syn-diasteroisomer the coupling constant is 7.7
Hz.12b For all O-silylated β-hydroxy-α-amino esters synthe-
sized by our group (compounds 30–36, Table 3), we ob-
served coupling constants varying from 5.5 to 6.0 Hz, which
confirms the anti relative configuration for the major dias-
tereoisomers. The anti-diastereoselectivity could be ratio-
nalized from the chelate model (Figure 2) proposed by
Cram34 and previously reported by our group for other re-
actions.9
Moving to broaden the scope and applicability of this
method, we decided to synthesize several racemic noncod-
ed α-amino acids. For this purpose, MBH adducts 7, 8, 10,
and 12–15 (see Table 1) were treated with acetyl chloride in
the presence of triethylamine to give the corresponding
acetylated products 38–44 in good to excellent yields (Table
4). The acetylated MBH adducts 38–44 were then deoxy-
genated under mild conditions35 to provide the enoate de-
rivatives 45–51 in good overall yields (ranging from 63–87%
over 2 steps) (Table 4).
The substituted enoates 45–51 were then subjected to
the same sequence of reactions described previously for the
synthesis of β-hydroxy-α-amino esters. The methanolic
solutions of compounds 45–51 were treated with a flow of
ozone at –78 °C for a few minutes (10–30 min), followed by
the addition of a large excess of dimethyl sulfide. After a
couple of hours, the crude α-keto esters were then reacted
with hydroxylamine hydrochloride and pyridine at 60 °C to
afford the corresponding oximes in good overall yields. For
all cases, we were not able to observe a mixture of isomeric
oximes. After chromatographic filtration, the oximes were
reduced by treatment with a mixture of MoCl5, NaBH3CN,
and NaHSO4·H2O to provide the corresponding racemic
noncoded amino esters in good overall yields (ranging from
46 to 61% over 2 steps) (Table 5).
Figure 2 DFT optimized structure for a Cram-chelate complex with a
MoCl4 fragment coordinated to 26 (bottom view). The bulky TBS group
is presented as a space-filling model. The highlighted carbon is the reac-
tion center for hydride.
In order to evaluate the Cram-chelate model, DFT calcu-
lations were performed for compound 26 coordinated to a
[MoCl4]+ fragment. Two modes of coordination were inves-
tigated, through the oxygen of the OTBS protecting group
and either with the N(oxyimino) or with the O(oxymino).
Several attempts were performed to obtain a N-bonded
complex, but in all cases, the starting geometries with the
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H. Ullah et al.
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overall yields, ranging from 30 to 53%. To our knowledge,
this is the first report on the synthesis of α-amino esters
from Morita–Baylis–Hillman adducts.
Table 4 Acetylation of MBH Adducts and Preparation of the Enoate
Derivativesa
OH
OAc
To demonstrate the feasibility of this approach, we de-
cided to use it in the total synthesis of a useful target. DOPA
is a noncoded amino acid, which is used in the treatment of
degenerative diseases such as Parkinson’s disease. In its ra-
cemic form, this amino acid was initially used to treat this
disease.36 Some years later, the S-enantiomer was identified
as the eutomer.37 Despite the existence of several chemical
and biotechnological asymmetric approaches to the syn-
thesis of this compound,38 its chemical resolution is very
easy to perform on a large scale, which justifies the devel-
opment of racemic strategies. Thus, the α-amino ester 65
was treated in a mixture of glacial acetic acid and phenol in
a solution of hydrochloric acid (6 mol/L) to provide racemic
DOPA as a sole compound in 63% yield (Scheme 3).
b
a
CO2Me
CO2Me
CO2Me
R
R
R
38–44
MBH adducts
7, 8, 10, 12–15
enoates
45–51
Entry MBH adduct, R
Acetylated MBH, Enoate,
yield (%)b
yield (%)b
1
2
3
4
5
6
7
7, 4-t-BuC6H4
8, Ph
38, 81
39, 70
40, 92
41, 75
42, 87
43, 71
44, 75
45, 94
46, 92
47, 95
48, >93
49, 94
50, 90
51, 89
10, 3-ClC6H4
12, 4-ClC6H4
13, 4-BrC6H4
14, 3,4,5-(MeO)3C6H2
15, piperonyl
HO
CO2H
NH2
CO2Et
NH2
O
O
a
a Reaction conditions: a) AcCl, Et3N, CH2Cl2, r.t., 2 h; b) DABCO, NaBH4,
THF–H2O (3:1).
HO
b Yields refer to isolated and purified products.
( )-α-amino ester 65
( )-DOPA (66)
Scheme 3 Preparation of racemic DOPA from Morita–Baylis–Hillman
adduct. Reagents and conditions: a) glacial AcOH, phenol, HCl (6 mol/L),
65%.
Table 5 Synthesis of Noncoded Racemic α-Amino Esters from MBH Ad-
ductsa
b
a
CO2Me
CO2Me
OH
CO2Me
NH2
DOPA in its racemic form was prepared in six steps from
MBH adducts, with an overall yield of 19%. The sequence is
very simple and straightforward. Because the commercial
availability of both enantiomers of a given amino acid is al-
ways interesting and considering that the chemical resolu-
tion is as yet a valid strategy to obtain them, the method
described herein could be considered as an alternative to
obtain this class of compounds.
In conclusion, we have reported an efficient and highly
diastereoselective approach for the synthesis of anti-β-hy-
droxy-α-amino acid esters. These anti-β-hydroxy-α-amino
acid esters were obtained in a sequence of three steps from
MBH adducts in good to excellent overall yields (ranging
from 85 to 96%) with high anti-stereoselectivity. Addition-
ally, this is the first report directly describing the synthesis
of anti-β-hydroxy-α-amino acid esters from MBH adducts.
Theoretical calculations have allowed the rationalization
for the attained diastereoselectivity. As far as we know, this
is the first report dealing with calculations involving Mo
salts in the diastereoselective reduction of oximes.
R
R
R
N
45–51
52–58
( )-α-amino esters
59–65
Entry
Enoate, R
Oxime,
Amino ester,
yield (%)b,c
yield (%)b
1
2
3
4
5
6
7
45, 4-t-BuC6H4
46, Ph
52, 94b
53, 92
54, 95
55, 91
56, 90
57, 94
58, 88
59, 64
60, 59
61, 65
62, 61
63, 63
64, 64
65, 52
47, 3-ClC6H4
48, 4-ClC6H4
49, 4-BrC6H4
50, 3,4,5-(MeO)3C6H2
51, piperonyld
a Reaction conditions: a) i. O3, MeOH, –78 °C, 15–30 min, ii. SMe2, 2 h, r.t.,
iii. NH2OH·HCl, pyridine, 60 °C, 30 min to 1 h; b) MoCl5, NaBH3CN,
NaHSO4·H2O, EtOH, reflux.
b Yields refer to isolated and purified products.
c We observed a small amount of hydrolysis products during the chromato-
graphic purification. The corresponding amino acids are much more polar
than the ester and likely stay retained on the silica gel column.
d In this particular case, the ethyl amino ester derivatives were also synthe-
sized in 87% and 60% yield, respectively.
A simple and easy extension of this methodology has
also allowed for the synthesis of racemic noncoded α-ami-
no esters in good overall yields. The synthetic applicability
of this sequence was demonstrated through the racemic
synthesis of DOPA. To the best of our knowledge, this is also
the first report of the synthesis of this α-amino acid from a
Morita–Baylis–Hillman adduct.
The entire synthetic sequence is very simple and direct.
The noncoded amino esters were synthesized in their race-
mic versions in four steps from the MBH adducts in good
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H. Ullah et al.
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Synthesis
Other efforts to demonstrate the usefulness of this
method in the total synthesis of pharmacologically active
alkaloids are under way in our laboratory and the results
will be disclosed in due time. Efforts to reduce the oxyimino
intermediate in an asymmetric manner as well as to use the
α-keto esters as substrates for enzymatic reductive amina-
tion (by employing transaminases) are ongoing in our labo-
ratory, and the results will be disclosed as soon as possible.
(±)-Methyl 3-[(tert-Butyldimethylsilyl)oxy]-3-(4-methoxyphenyl)-
2-(N-hydroxyimino)propanoate (24)
Reaction time: 70 min; yield: 640 mg (91%); viscous yellow oil.
IR (neat): 3200, 3479, 2954, 2928, 2856, 1735, 1611, 1520, 1445, 1434
cm–1
.
1H NMR (250 MHz, CDCl3): δ = –0.03 (s, 3 H), 0.08 (s, 3 H), 0.89 (s, 9
H), 3.78 (s, 3 H), 3.80 (s, 3 H), 5.51 (s, 1 H), 6.87 (d, J = 10 Hz, 2 H), 7.27
(m, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = –5.0, –4.8, 18.3, 25.7, 52.1, 55.3, 73.3,
113.7, 113.8, 114.4, 127.5, 127.8, 128.7, 131.9, 149.9, 153.9, 159.4,
163.1.
The reaction progress was monitored by TLC on silica gel (aluminum
foils) and spotted under UV light (254 nm), followed by staining with
ethanolic 25% phosphomolybdic solution or aqueous KMnO4. Purifi-
cation by column chromatography was carried out on silica gel (70–
230 or 230–400 Mesh). 1H NMR spectra were recorded at 250 and 500
MHz and the 13C NMR spectra at 62.5 and 125 MHz, in CDCl3 or
CD3OD at r.t. Chemical shifts (δ) were reported in ppm and the cou-
pling constants (J) in hertz (Hz). Standard abbreviations were used to
assign the multiplicities of NMR signals. High-resolution mass spectra
were recorded using Q-TOF Micromass equipment (Waters, UK). Com-
pounds were named according to IUPAC rules using the program
MarvinSketch 5.5.0.1.
HRMS (ESI): m/z [M + Na]+ calcd for C17H27NO5Si + Na: 376.1556;
found: 376.1548.
Methyl (±)-3-[(tert-Butyldimethylsilyl)oxy]-3-(4-tert-butylphe-
nyl)-2-(N-hydroxyimino)propanoate (25)
Reaction time: 80 min; yield: 746 mg (98%); yellow viscous oil.
IR (neat): 3381, 2968, 2931, 2869, 1735, 1483, 1268, 1088 cm–1
.
1H NMR (500 MHz, CDCl3): δ = –0.01 (s, 6 H), 1.29 (s, 18 H), 3.86 (s, 3
H), 5.27 (s, 1 H), 6.16 (s, 1 H), 5.51 (s, 1 H), 7.50 (m, 4 H), 7.27.
13C NMR (125 MHz, CDCl3): δ = –0.9, 0.0, 29.0, 31.5, 52.25, 68.3, 73.0,
127.0, 128.5, 137.0, 151.0, 152.6, 159.4, 163.5.
Oxyimino Esters 23–29; General Procedure
HRMS (ESI): m/z [M + Na]+ calcd for C20H33NO4Si + Na: 402.2071;
Into a solution of the respective silylated MBH adduct 16–22 (2
mmol) in MeOH (30 mL), was bubbled a flow of ozone (3.5 g O3/h), at
–78 °C. The progress of the reaction was followed by TLC (eluent:
(EtOAc–hexane, 20:80). After the completion of the reaction (15–30
min), to the resulting solution was added Me2S (10 equiv) at –78 °C
and reaction mixture was warmed to r.t. and stirred for 1–2 h. Cau-
tion! Before adding Me2S, the reaction medium was purged with N2
for 15 min at –78 °C in order to remove the excess of ozone. After this
time, 2 to 3 drops of pyridine and NH2OH·HCl (1 equiv) were added
and the reaction flask was fitted with a reflux condenser and the mix-
ture was refluxed for 30 min to 1 h.39 The progress of the reaction was
monitored by TLC (eluent: EtOAc–hexane, 40:60). After completion of
the reaction, the solvents were removed under vacuum and the resi-
due was partitioned between CH2Cl2 and H2O (1:1, 20 mL). The phases
were separated and the aqueous phase was extracted with CH2Cl2 (2 ×
20 mL). The organic phases were combined, dried (Na2SO4), filtered,
and then concentrated to yield the corresponding oximes. In the most
cases, the products showed purity sufficient to be used in the next
step without any further purification. If necessary, chromatographic
purification on silica gel can be carried out.
found: 402.2056.
Methyl (±)-3-[(tert-Butyldimethylsilyl)oxy]-2-(N-hydroxyimino)-
3-phenylpropanoate (26)
Reaction time: 60 min; yield: 608 mg (94%); colorless viscous oil.
IR (neat): 3321, 2954, 2920, 2857, 1747, 1455, 1290, 1246, 1140 cm–1
1H NMR (250 MHz, CDCl3): δ = 0.01 (s, 3 H), 0.09 (s, 3 H), 0.91 (s, 9 H),
3.76 (s, 3 H), 5.56 (s, 1 H), 7.22–7.41 (m, 5 H), 9.28 (s, 1 H).
13C NMR (62.5 MHz, CDCl3): δ = –5.0, -4.9, 18.3, 25.8, 52.1, 73.6, 126.5,
128.1, 128.3, 139.7, 153.6, 162.8.
HRMS (ESI): m/z [M + H]+ calcd for C16H25NO4Si + Na: 346.145; found:
346.1416.
.
Methyl (±)-3-[(tert-butyldimethylsilyl)oxy]-2-(N-hydroxyimi-
no)pentanoate (27)
Reaction time: 45 min; yield: 494 mg (90%); colorless oil.
IR (neat): 3200–3400, 2955, 2931, 2859, 1742, 1463, 1438, 1310,
1257, 1159, 1106 cm–1
.
1H NMR (250 MHz, CDCl3): δ = 0.05 (s, 6 H), 0.86–0.89 (s, 9 H), 0.86–
0.89 (m, 3 H), 1.68–1.80 (m, 3 H), 3.82 (s, 3 H), 4.27 (t, J = 6.7 Hz, 1 H),
9.28 (br, 1 H).
13C NMR (62,5 MHz, CDCl3): δ = –5.3, –5.1, 9.5, 17.9, 25.5, 28.8, 51.7,
73.1, 154.1, 162.9.
Methyl (±)-3-(6-Bromo-2H-1,3-benzodioxol-5-yl)-3-[(tert-butyldi-
methylsilyl)oxy]-2-(N-hydroxyimino)propanoate (23)
Reaction time: 60 min; yield: 395 mg (89%); colorless oil.
IR (neat): 3273, 2954, 2930, 2857, 1746, 1474, 1503, 1408, 1240 cm–1
.
1H NMR (250 MHz, CDCl3): δ = –0.10 (s, 3 H), 0.04 (s, 3 H), 0.83 (s, 9
H), 3.81 (s, 3 H), 5.85 (s, 1 H), 5.93 (d, J = 10 Hz, 2 H), 6.90 (s, 2 H), 7.02
(s, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C12H26NO4Si: 276.163; found:
276.1604.
13C NMR (62.5 MHz, CDCl3): δ = –5.0, –4.6, 18.3, 25.8, 29.9, 52.5, 72.3,
102.1, 109.5, 112.3, 112.8, 132.5, 147.7, 148.4, 151.8, 163.0.
HRMS (ESI): m/z [M + Na]+ calcd for C17H24BrNO6Si + Na : 470.0436;
Methyl (±)-3-[(tert-Butyldimethylsilyl)oxy]-3-(3-chlorophenyl)-2-
(N-hydroxyimino)propanoate (28)
Reaction time: 40 min; yield: 686 mg (96%); yellow viscous oil.
found: 470.0395.
IR (neat): 3200–3400, 2954, 2935, 2858, 1743, 1596, 1575, 1472,
1445, 1316 cm–1
.
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1H NMR (250 MHz, CDCl3): δ = 0.00 (s, 3 H), 0.09 (s, 6 H), 0.89 (s, 9 H),
13C NMR (62.5 MHz, CDCl3): δ = –5.1, –4.4, 18.3, 25.9, 29.93, 52.0,
3.74 (s, 3 H), 5.51 (s, 1 H), 7.24–7.38 (m, 4 H).
55.4, 62.5, 113.8, 128.3, 132.8, 159.6, 173.9.
13C NMR (62.5 MHz, CDCl3): δ = –4.9, 18.2, 25.7, 52.4, 73.0, 124.3,
HRMS (ESI): m/z [M + H]+ calcd for C17H30NO4Si: 340.1944; found:
126.2, 127.9, 129.5, 134.1, 142.1, 153.1, 162.6.
340.1945
HRMS (ESI): m/z [M + H]+ calcd for C16H25ClNO4Si: 358.124; found:
358.1244.
Methyl (±)-anti-2-Amino-3-(tert-butyldimethylsilyloxy)-3-(4-tert-
butylphenyl)propanoate (32)
Reaction time: 45 min, yield: 340 mg (93%); brown oil.
Methyl (±)-3-(tert-Butyldimethylsilyloxy)-2-(N-hydroxyimino)-3-
(4-nitrophenyl)propanoate (29)
IR (neat): 3392, 2949, 2925, 2855, 1742, 1462, 1363, 1258, 1166, 1088
Reaction time: 70 min; yield: 588 mg (80%); reddish brown viscous
oil.
cm–1
.
1H NMR (250 MHz, CDCl3): δ = –0.21 (s, 3 H), –0.02 (s, 3 H), 0.84 (s, 9
H), 1.28 (s, 9 H), 3.63 (d, J = 6.5 Hz, 1 H), 3.68 (br s, 1 H), 4.75 (d, J = 6.7
Hz, 1 H), 7.16 (d, J = 8.2 Hz, 2 H), 7.30 (d, J = 8.2 Hz, 2 H).
IR (neat): 3392, 2949, 2925, 2855, 2857, 1742, 1462, 1362, 1258,
1166, 1088 cm–1
.
1H NMR (250 MHz, CDCl3): δ = –0.005 (s, 3 H), 0.08 (s, 3 H), 0.89 (s, 9
H), 3.73 (s, 3 H), 5.60 (s, 1 H), 7.54 (d, J = 8.5 Hz, 2 H), 8.16 (d, J = 8.8
Hz, 2 H), 9.66 (s, 1 H).
13C NMR (62.5 MHz, CDCl3): δ = –4.9, 18.3, 25.7, 52.4, 55.3, 73.1,
123.7, 127.2, 147.3, 147.8, 152.1, 128.7, 131.9, 149.9, 153.9, 159.4,
162.4.
13C NMR (125 MHz, CDCl3): δ = –5.1, –4.1, 18.2, 25.9, 29.9, 31.5, 34.7,
51.9, 52.0, 62.4, 125.2, 126.8, 135.5, 151.1, 173.9.
HRMS (ESI): m/z [M + H]+ calcd for C20H36NO3Si: 366.2459; found:
366.2459.
Methyl (±)-anti-2-Amino-3-[(tert-butyldimethylsilyl)oxy]-3-phen-
ylpropanoate (33)
HRMS (ESI): m/z [M + H]+ calcd for C16H25N2O6Si: 369.1467; found:
369.1467.
Reaction time: 40 min; yield: 287 mg (93%); viscous colorless oil.
IR (neat): 3483, 2954, 2920, 2854, 1720, 1477, 1447, 1234, 1038 cm–1
.
Silylated anti-β-Hydroxy-α-amino Esters 30–36; General Proce-
dure
1H NMR (500 MHz, CDCl3): δ = –0.14 (s, 3 H), 0.07 (s, 3 H), 0.94 (s, 9
H), 3.41 (s, 3 H), 3.68 (d, J = 7.0 Hz, 1 H), 4.79 (d, J = 7.0 Hz, 1 H), 7.05–
7.22 (m, 5 H).
13C NMR (62.5 MHz, CDCl3): δ = -5.3, –4.7, 18.0, 25.6, 51.7, 62.0, 76.5,
126.0, 126.8, 128.1, 140.3, 173.3.
To a stirred solution of the respective oxyimino ester (1 mmol, 1
equiv) in EtOH (2 mL for 1 mmol of starting material) was carefully
added a solid mixture of NaBH3CN (4 equiv), MoCl5 (1 equiv) and
NaHSO4·H2O (3 equiv). The resultant mixture was stirred under reflux
from 50 min up to 1 h. The reaction was monitored by TLC (eluent:
EtOAc–hexane, 20:80), and after the end of the reaction, 5% aq
NaHCO3 (15 mL) was added and the mixture was extracted with
CH2Cl2 (3 × 15 mL). The extracts were combined, dried (Na2SO4), fil-
tered, and concentrated under reduced pressure. The crude product
was purified by flash chromatography on silica gel (eluent: gradient
of EtOAc–hexane, varying from 15:85 up to 80:20 v/v).
HRMS (ESI): m/z [M + H]+ calcd for C16H28NO3Si: 310.1838; found:
310.1826.
Methyl (±)-anti-2-Amino-3-[(tert-butyldimethylsilyl)oxy]penta-
noate (34)
Reaction time: 50 min; yield: 188 mg (72%); colorless oil.
IR (neat): 3400, 2955, 2931, 2859, 1742, 1463, 1438, 1253, 1172,
1106, 1058 cm–1
.
Methyl (±)-anti-2-Amino-3-(6-bromo-2H-1,3-benzodioxol-5-yl)-3-
[(tert-butyldimethylsilyl)oxy]propanoate (30)
1H NMR (250 MHz, CDCl3): δ = 0.02 (s, 6 H), 0.83 (s, 9 H), 1.25–1.71
(m, 5 H), 3.54 (d, J = 4.5 Hz, 1 H), 3.64 (s, 1 H), 3.75–3.79 (m, 1 H).
13C NMR (62.5 MHz, CDCl3): δ = –4.6, –4.3, 9.8, 18.1, 25.8, 51.9, 59.1,
Reaction time: 55 min; yield: 380 mg (88%); yellow oil.
IR (neat): 3627, 2950, 2924, 2853, 1740, 1510, 1475, 1250 cm–1
.
75.7, 173.9.
1H NMR (500 MHz, CDCl3): δ = –0.17 (s, 3 H), 0.05 (s, 3 H), 0.85 (s, 9
H), 3.57 (d, J = 7.0 Hz, 1 H), 3.70 (s, 3 H), 5.15 (d, J = 7.0 Hz, 1 H), 5.98
(dd, J = 1.0, 9.2 Hz, 2 H), 6.95 (s, 1 H), 6.96 (s, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C12H28NO3Si: 262.1838; found:
262.1833.
13C NMR (62.5 MHz, CDCl3): δ = –5.4, –4.8, 17.8, 25.5, 51.6, 61.8, 75.6,
101.7, 108.2, 111.9, 113.3, 133.8, 147.5, 147.9, 173.5.
HRMS (ESI): m/z [M + H]+ calcd for C17H27BrNO5Si: 434.0824; found:
434.0831.
Methyl (±)-anti-2-Amino-3-[(tert-butyldimethylsilyl)oxy]-3-(3-
chlorophenyl)propanoate (35)
Reaction time: 40 min; yield: 330 mg (96%); viscous yellow oil.
IR (neat): 3392, 3388, 2972, 2915, 2857, 1752, 1598, 1483, 1436,
1274, 1102 cm–1
.
Methyl (±)-anti-2-Amino-3-[(tert-butyldimethylsilyl)oxy]-3-(4-
methoxyphenyl)propanoate (31)
1H NMR (250 MHz, CDCl3): δ = –0.14 (s, 3 H), 0.04 (s, 3 H), 0.88 (s, 9
H), 3.51 (s, 1 H), 3.65 (s, 3 H), 3.69 (d, J = 6.0 Hz, 1 H), 4.81 (d, J = 6.3
Hz, 1 H), 7.14–7.26 (m, 4 H).
13C NMR (62.5 MHz, CDCl3): δ = –5.1, –4.5, 18.2, 25.8, 52.0, 62.3,
125.22, 127.2, 128.3, 129.6, 134.4, 142.9, 173.4.
Reaction time: 50 min; yield: 322 mg (95%); yellow oil.
IR (neat): 3371, 2955, 2929, 2856, 1741, 1683, 1611, 1525, 1463, 1439
cm–1
.
1H NMR (250 MHz, CDCl3): δ = –0.18 (s, 3 H), 0.07 (s, 3 H), 0.85 (s, 9
H), 3.63 (d, J = 6.5 Hz, 1 H), 3.70 (s, 3 H), 3.80 (s, 3 H), 4.76 (d, J = 6.3
Hz, 1 H), 6.86 (d, J = 8.7 Hz, 2 H), 7.20 (d, J = 8.5 Hz, 2 H).
HRMS (ESI): m/z [M + H]+ calcd for C16H27ClNO3Si: 344.1449; found:
344.1450.
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Methyl (±)-anti-2-Amino-3-(tert-butyldimethylsilyloxy)-3-(4-ni-
Ethyl 2-(2H-1,3-Benzodioxol-5-ylmethyl)prop-2-enoate (51)
trophenyl)propanoate (36)
Yield: 392 mg (89%); colorless oil.
Reaction time: 40 min; yield: 283 mg (80%); reddish brown oil.
IR (neat): 3002, 2991, 1736, 1240 cm–1
.
IR (neat): 3382, 2957 2929, 2860, 1741, 1572, 1524, 1346, 1258, 1087
1H NMR (250 MHz, CDCl3): δ = 1.27 (t, J = 7.1 Hz, 3 H), 3.54 (s, 2 H),
4.17 (q, J = 7.1 Hz 2 H), 5.45 (d, J = 1.2 Hz, 1 H), 5.91 (s, 2 H), 6.21 (s, 1
H), 6.59–6.74 (m, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 14.3, 37.9, 60.9, 101.0, 108.3, 109.6,
122.1, 125.9, 132,7, 140.7, 146.2, 147.8, 167.0.
cm–1
.
1H NMR (250 MHz, CDCl3): δ = –0.16 (s, 3 H), 0.04 (s, 3 H), 0.86 (s, 9
H), 3.67 (br s, 4 H), 4.93 (s, J = 6.0 Hz 1 H), 7.46 (d, J = 8.8 Hz, 2 H), 8.18
(d, J = 8.8 Hz, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = –5.0, –4.5, 18.2, 25.8, 52.2, 62.2, 76.6,
123.5, 127.9, 147.9, 147.5, 173.2.
HRMS (ESI): m/z [M + H]+ calcd for C13H14O4: 235.0970; found:
235.0983.
HRMS (ESI): m/z [M + H]+ calcd for C16H27N2O5Si: 355.1684; found:
355.1683.
Ozonolysis and Oximation of Enoates 52–58; General Procedure
Ozonolysis of the MBH adducts 45–51 (2 mmol, 1 equiv) was carried
out similar to the silylated MBH adducts 16–22 at –78 °C for 15–30
min to give the corresponding α-keto esters. To the resulting solution,
hydroxylamine hydrochloride (1.5 equiv) and pyridine (1.0 mL) were
added and the mixture was stirred at r.t. for 50 min. The solvent was
removed and the crude residue was purified by silica gel flash chro-
matography (EtOAc–hexane, 20:80) to afford the corresponding non-
coded α-amino esters. Compounds 53, 55, 57, and 58 are known and
their spectroscopic data are in agreement with the data available in
the literature. For details see Supporting Information. The analytical
and spectral data of the unknown compounds are given below.
Anti-β-hydroxy-α-amino Acid Esters; General Procedure
To a solution of the appropriate β-hydroxy-α-amino ester (3.0 mmol.)
in anhydrous THF (20 mL) was added a solution of TBAF (1 mol/L in
THF, 3.6 mmol) at 0 °C. The resulting mixture was stirred for 30 min.
The solvent was evaporated and residue was dissolved in EtOAc (15
mL). The organic layer was washed with distilled H2O (15 mL), brine
(2 × 15 mL), dried (Na2SO4), and the solvent was removed under vacu-
um. The residue was filtered through silica gel (EtOAc–hexanes,
30:70) to provide the corresponding amino acid ester.
Methyl (±)-anti-2-Amino-3-hydroxy-3-phenylpropanoate (37)
Methyl 3-(4-tert-Butylphenyl)-2-(N-hydroxyimino)propanoate
(52)
Reaction time: 30 min; yield: 538 mg (92%); yellow oil.
IR (neat): 3600, 3299, 2954, 1733, 1453, 1437, 1206, 1103, 1053 cm–1
1H NMR (500 MHz, CD3OD): δ = 3.66 (s, 3 H), 3.72 (d, J = 5.5 Hz, 1 H),
4.88 (d, J = 6.0 Hz, 1 H), 7.27–7.34 (m, 5 H).
13C NMR (125 MHz, CDCl3): δ = 52.4, 61.9, 76.0, 127.9, 129.1, 129.4,
.
Yield: 442 mg (94%); white solid; mp 165–167 °C.
1H NMR (250 MHz, CD3OD): δ = 1.27 (s, 9 H), 3.88 (s, 2 H), 7.17 (d,
J = 8.0 Hz, 2 H), 7.26 (d, J = 8.0 Hz, 2 H).
13C NMR (62.5 MHz, CD3OD): δ = 28.2, 30.3, 33.7, 124.4, 129.0, 134.7,
148.7, 153.7, 162.8.
141.9, 174.7.
HRMS (ESI): m/z [M + H]+ calcd for C10H14NO3: 196.0974; found:
196.0987.
HRMS (ESI): m/z [M + H]+ calcd for C13H18NO3: 236.1287; found
236.1272.
Deoxygenation of the MBH Adducts and Preparation of Enoates
45–51; General Procedure
Methyl 3-(3-Chlorophenyl)-2-(N-hydroxyimino)propanoate (54)
Yield: 431 mg (95%); white solid; mp 90–92 °C.
1H NMR (250 MHz, CDCl3): δ = 3.84 (s, 3 H), 3.97 (s, 2 H), 7.28–7.35
(m, 3 H), 7.67–7.76 (m, 1 H).
13C NMR (62.5 MHz, CDCl3): δ = 30.1, 52.8, 126.9, 127.3, 129.2, 129.7,
To a mixture of a given acetylated MBH adduct (2.0 mmol) in THF–
H2O (3:1, 4 mL) was added DABCO (2.0 mmol). The resulting solution
was stirred at r.t. for 15 min. Then, NaBH (2.0 mmol) was added at r.t.
and the resulting mixture was stirred for 15 min. The solvent was re-
moved and the crude residue was purified by flash chromatography
over silica gel (hexane–5% EtOAc) to afford the corresponding enoates.
Compounds 45–49 are known and their spectroscopic data are in
agreement with the data available in the literature. For details see
Supporting Information. The analytical and spectral data of the un-
known compounds are given below.
134.2, 137.5, 150.2, 163.6.
Methyl 3-(4-Bromophenyl)-2-(N-hydroxyimino)propanoate (56)
Yield: 488 mg (90%); colorless oil.
1H NMR (250 MHz, CDCl3): δ = 3.76 (s, 3 H), 3.90 (s, 2 H), 7.13–7.19 (d,
J = 7.8 Hz, 2 H), 7.31–7.36 (d, J = 7.8 Hz, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 30.0, 52.7, 120.4, 130.9, 131.5, 134.9,
Methyl 2-[(3,4,5-Trimethoxyphenyl)methyl]prop-2-enoate (50)
150.1, 163.9.
Yield: 479 mg (90%); colorless oil.
HRMS (ESI): m/z [M + H]+ calcd for C10H11BrNO3: 271.9922; found:
IR (neat): 3010, 2996, 1741, 1445, 1236 cm–1
.
271.8000.
1H NMR (250 MHz, CDCl3): δ = 3.57 (s, 2 H), 3.75 (s, 3 H), 3.82 (s, 3 H),
3.83 (s, 6 H), 5.50 (s, 1 H), 6.24 (s, 1 H), 6.41 (s, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 38.2, 51.7, 55.9, 60.6, 105.8, 126.1,
134.2, 136.4, 139.8, 153.0, 167.1.
HRMS (ESI): m/z [M + H]+ calcd for C14H19O5: 267.1232; found:
α-Amino Esters/Acids 59–65; General Procedure
See Supporting Information for complete experimental details and
spectral data.
267.1199.
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Theoretical Calculations
S. M. J. Antibiot. 1992, 45, 1692. For some recent examples
related to the total synthesis of sphingofungin E, see:
(c) Martinkova, M.; Gonda, J.; Raschmanova, J. S.; Slaninkova,
M.; Kuchar, J. Carbohydr. Res. 2010, 345, 2427. (d) Ohfune, Y.;
Shinada, T. Eur. J. Org. Chem. 2005, 5127. (e) Kang, S. H.; Kang, S.
Y.; Lee, H. S.; Burlass, A. J. Chem. Rev. 2005, 105, 4537.
(f) Nakamura, T.; Shiozaki, M. Tetrahedron 2002, 58, 8779.
(g) Oishi, T.; Ando, K.; Inomiya, K.; Sato, H.; Iida, M.; Chida, N.
Bull. Chem. Soc. Jpn. 2002, 75, 1927. (h) Oishi, T.; Ando, K.;
Inomiya, K.; Sato, H.; Iida, M.; Chida, N. Org. Lett. 2002, 4, 151.
(i) Nakamura, T.; Shiozaki, M. Tetrahedron Lett. 2001, 42, 2701.
(j) Wang, B.; Yu, X. M.; Lin, G. Q. Synlett 2001, 904.
Density functional theory (DFT) calculations were carried out using
PBE040 gradient-corrected hybrid to solve the Kohn–Sham equations
with a 10–5 a.u. convergence criterion for the density change. The
choice of PBE0 is based on the fact that this functional gives better ge-
ometries than B3LYP for coordination compounds.41 The LANL2DZ ef-
fective core potential42 was used for Mo and the atomic 6-31G(d) ba-
sis set43 for all other atoms. All calculations were performed using
GAMESS software44 (version Jan 12, 2009 R3 for 64 bit) and geome-
tries were optimized with a convergence criterion of 10–4 a.u. in a
conjugated gradient algorithm without constraints. Vibrational fre-
quency analyses were performed at the same level of theory to con-
firm the structures as minima of the potential energy surfaces (PES)
showing no imaginary frequencies. All the models and figures were
plotted using Jmol.45
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Acknowledgment
The authors thank (FAPESP) and the CNPq for the financial support
and CENAPAD-SP for computing time. H.U. thanks TWAS/CNPq for the
fellowship. M.T.R. Jr. thanks CNPq for the fellowship. F.C. and A.L.B.F.
also thank CNPq for the research fellowship.
Supporting Information
Supporting information for this article is available online at
(8) Shen, H.-Y.; Tian, G.-L.; Ye, Y.-H.; Wang, J. J. Mol. Catal. B 2005,
37, 26.
http://dx.doi.org/10.1055/s-0034-1378168.
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u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
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