Chiral octahedral complexes of cobalt(III) as "organic catalysts in disguise" for the asymmetric addition of a glycine schiff base ester to activated olefins

Article abstract of DOI:10.1002/adsc.201400091

Stereochemically inert and positively charged chiral complexes of cobalt(III) prepared from Schiff bases derived from chiral diamines and salicylaldehydes were shown to be efficient catalysts of the benchmark asymmetric phase-transfer Michael addition of nine activated olefins to O'Donnell's substrate. The reaction products had enantiomeric purities of up to 96%. DFT calculations were invoked to rationalize the stereochemistry of the addition.

Full text of DOI:10.1002/adsc.201400091

FULL PAPERS
DOI: 10.1002/adsc.201400091
Chiral Octahedral Complexes of Cobalt(III) as “Organic Catalysts
G
in Disguise” for the Asymmetric Addition of a Glycine Schiff
Base Ester to Activated Olefins
Victor I. Ma,a Michael North,b Vladimir A. Larionov,a Ivan V. Fedyanin,a
Tatyana F. Savel’yeva,a Margarita A. Moscalenko,a Alexander F. Smolyakov,a
and Yuri N. Belokona,*
a
Nesmeyanov Institute of Organoelement Compounds, Vavilov 28, 119991 Moscow, Russia
Fax : (+7)-499-135-5085; e-mail: yubel@ineos.ac.ru
Green Chemistry Centre of Excellence, Department of Chemistry, University of York, Heslington, York, YO10 5DD,
b
U.K.
Received: January 24, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400091.
Abstract: Stereochemically inert and positively strate. The reaction products had enantiomeric puri-
charged chiral complexes of cobaltACTHNUTRGNEUG(N III) prepared ties of up to 96%. DFT calculations were invoked to
from Schiff bases derived from chiral diamines and rationalize the stereochemistry of the addition.
salicylaldehydes were shown to be efficient catalysts
of the benchmark asymmetric phase-transfer Michael Keywords: amino acids; asymmetric phase-transfer
addition of nine activated olefins to OꢀDonnellꢀs sub- catalysis; cobalt; Michael addition; Schiff bases
Introduction
ma.[14] Chiral bifunctional catalysts, containing both
acidic and basic centres (Figure 1), were elaborated
The conjugate addition of nucleophiles to electrophil- and employed by Y. Takemoto in a set of Michael ad-
ic alkenes is one of the most popular ways to build dition reactions.[15] Chiral positively charged quaterna-
[1]
À
À
C C and C heteroatom bonds. Catalytic asymmet- ry ammonium salts were successfully employed in nu-
ric ways to perform these reactions are the most im- merous 1,4-addition reactions under phase-transfer
portant relatively recent development in the field and conditions and the subject among others was recently
are already applied in industry.[2]
reviewed by K. Maruoka.[16] The subject is still being
Chiral complexes of transition, rare- and alkaline- actively explored and novel positively charged chiral
earth metals were and still are widely used as catalysts
in numerous asymmetric conjugate addition reactions.
Generally, the complexes serve as Lewis acids with
the central metal ion (or ions), providing a free coor-
dination site (or sites) for substrate activation and the
chiral ligands, ensuring asymmetric induction in the
transition state.[3–10]
Recently, asymmetric organocatalysis has emerged
as a highly efficient, environmentally friendly way of
approaching asymmetric conjugate addition reactions,
avoiding any use of metals. The literature dealing
with this approach was fully reviewed by Najera[11]
and Tsogoeva[12] in 2007. Use of weak hydrogen bond
donors (such as thiourea derivatives) or relatively
strong chiral Brønsted acids as catalysts for numerous
asymmetric organic reactions, including 1,4-additions,
Figure 1. Hydrogen bond donating precatalysts of 1,4-addi-
was reviewed by Doyle and Jacobsen[13] and by Akiya- tion reactions.
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Victor I. Maleev et al.
Figure 2. Structures of catalysts 1–5 (a: R’=R’’=t-Bu; b: R’=t-Bu, R’’=H; c: R’=Ph, R’’=H; d: R’=R’’=H).
organocatalysts elaborated by K. K. Hii and C.-H. strate) with alkyl halides.[25] We believed that the
Tan were applied for the asymmetric synthesis of glu- complexes provided a set of rigidly spatially oriented
tamic acid derivatives.[17,18]
hydrogen bonds to activate and position the sub-
Further development in the field was reported by strates and/or bases similar to Ooiꢀs catalyst.
T. Ooi who introduced chiral tetraaminophosphonium
An additional bonus of the cobaltACHTNGUTERN(UNG III) complex
À
salts (Figure 1) as catalysts for asymmetric C C bond system was its metal-centred chirality, furnishing addi-
forming reactions.[19,20] The catalyst combined hydro- tional facets of enantiomeric recognition. One could
gen bond donating ability with a positive charge. reasonably expect that this family of complexes could
Asymmetric 1,4-addition of azlactones to activated be successfully applied to the asymmetric 1,4-addition
olefins was successfully catalyzed by a combination of of activated olefins to OꢀDonnellꢀs substrate, furnish-
the salt with a phenolate/phenol array[17] in a “charge- ing an efficient catalytic protocol for the asymmetric
assisted supramolecular catalytic way” according to synthesis of glutamic acid derivatives and other enan-
Lacour.[21]
tiomerically enriched non-protein amino acids. The
A new class of original “organic catalysts in dis- enantiomerically pure compounds are important
guise” was presented by papers reporting the use of building blocks and research tools in studying protein
inert, chiral at metal and positively charged com- properties.[26,27]
plexes as asymmetric catalysts.[22,23] The pioneering
study of Gladysz et al[23] dealt with the use of enantio-
pure Werner cation (Figure 1) as a precatalyst for ma- Results and Discussion
lonic ester Michael addition to cyclohexenone, result-
ing in a moderate 30% ee of the adduct. The authors Herein we describe an efficient application of chiral
postulated activation of the substrate by hydrogen complexes 1–5 (Figure 2) to the catalytic enantioselec-
bond donation from the chiral complex cation as tive Michael addition of OꢀDonnellꢀs substrate to a va-
a driving force for the conversion. Thus, it was not the riety of activated olefins (Scheme 1).
metal Lewis acidity that was the driving force for the
Initially, we examined the asymmetric Michael ad-
substrate activation, but the Brønsted acidity of the li- dition reaction of glycine Schiff base to methyl acry-
gands which was increased by their coordination with late. Different solvents were tested in the reaction
the central metal ion-Lewis acid. The concept of (Table 1, runs 1–8). The best solvent was found to be
“Lewis acid assisted Brønsted acid catalysis” was ear- dichloromethane (run 1). Toluene, dioxane, methyl
lier developed by Yamamoto.[24]
tert-butyl ether and acetonitrile gave reasonable
In previous work, we successfully elaborated the chemical yields (83–97%), but the enantioselectivity
chiral, positively charged, stereochemically inert com- was decreased (30–42% ee) (runs 2–5). Ether and
plexes of cobaltACHTUNGTRENNUNG(III) depicted in Figure 2 as chiral hexane (runs 6 and 7) gave good yields (83–89%), but
phase-transfer catalysts for efficient asymmetric alky- the enantioselectivities were poor (12–15% ee). The
lation of a glycine Schiff base ester (OꢀDonnel sub- use of THF (run 8) led to a worse chemical yield
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Chiral Octahedral Complexes of CobaltACTHNUTRGENUGN(III) as “Organic Catalysts in Disguise”
Table 1. Conjugate addition of OꢀDonnellꢀs substrate to
methyl acrylate at ambient temperature, promoted by
LACTHNUTRGNEUNG
(R,R)-1a.[a]
Run
Solvent
Base
Conversion/
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
CH2Cl2
toluene
1,4-dioxane
MeCN
MTBE
Et2O
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K3PO4
PhONa
NaOH
KOH
100/95
87/83
90/85
99/97
89/86
92/89
88/83
62/60
30/27
12/9
100/97
100/98
43/40
100/98
100/98
75 (S)
36 (S)
40 (S)
42 (S)
30 (S)
12 (S)
15 (S)
56 (S)
76 (S)
72 (S)
77 (S)
78 (S)
78 (S)
81 (S)
81 (S)
hexane
THF
9
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
10[d]
11
12
13[e]
14[f]
15[g]
Scheme 1. Asymmetric Michael addition of glycine Schiff
base to activated C=C bonds under phase-transfer condi-
tions promoted by positively charged chiral complexes of
KOH
KOH
KOH
cobalt
N
[a]
Reaction conditions: 30 mg (0.101 mmol) OꢀDonnellꢀs
substrate, 7.6 mg (0.0101 mmol, 10 mol%) catalyst
LACTHUNRTGNE(GNU R,R)-1a, 1 mL solvent, 3 equiv. of solid base
(0.303 mmol) and 3 equiv. of methyl acrylate
(0.303 mmol) for 2 h at room temperature.
The chemical yields of pure Michael adduct by weight
after purification by flash chromatography on silica.
Enantiomeric purity was established by CSP HPLC anal-
ysis of the alkylated product, the absolute configuration
was established as described in the text.
0.1 equiv. of PhONa (0.0101 mmol) was used.
0.8 mL of 1% aqueous solution of KOH was used for
1 h.
(60%), but the enantioselectivity was slightly in-
creased (56%). The reason behind this observation
may be the so-called halogen bonding effect.[28] The
solvent could solvate the intermediate enolate or the
initial complex providing additional stereochemical
bias in the reaction. Then, dichloromethane was
chosen to focus on the effect of bases in the addition
reaction. Generally, the strength of the base affected
the chemical yield in a predictable manner (compare
runs 9, 10 and 11–13), but the asymmetric induction
was slightly influenced by it with one equivalent of
solid potassium hydroxide giving the best results in
terms of both enantioselectivity and chemical yield
(run 14). The amount of added base could be effi-
ciently decreased to 0.1 equivalents (compare runs 14
[b]
[c]
[d]
[e]
[f]
1 equiv. KOH (0.101 mmol) was used for 1 h.
0.1 equiv. KOH (0.0101 mmol) was used for 1 h
[g]
and 15). The absolute configuration of the stereogenic moiety of the Schiff base to naphthol derivative 2
centre in 6a for all experiments was established to be (Table 2, run 5). In the case of 1d, derived from un-
S by chiral GC analysis of isolated glutamic acid from substituted salicylaldehyde, the asymmetric induction
the experiment of run 1 and then comparing the CSP decreased to 73% ee (Table 2, run 4). Complex D(S)-3
HPLC retention time of the parent 6a with that of the derived from (S)-aminomethylpyrrolidine was catalyt-
samples from the other experiments.
ically inactive (Table 2, run 6). Evidently, the presence
The optimal amount of the catalyst was found to be of four NH bonds in the complexes was a prerequisite
10% mol (see the Supporting Information, Table 1). for successful catalytic performance. Catalyst 4, de-
No racemisation was observed under the optimum rived from (R,R)-diphenylethylenediamine, although
conditions of the addition (see Table 2 in the support- catalytically active, produced no asymmetric induction
ing material).
in the reaction (Table 2, run 7). Catalysts 1 having D-
(S,S)-configuration furnished the product of (R)-con-
(R,R)-
Other catalysts 1–5 were tested in the reaction
under the conditions of Table 1, run 14, and the data figuration (Table 2, run 4) whereas 1 with LACHTUNGTRENNUNG
ACHTUNGTRENNUNG
are summarized in Table 2. In general, their catalytic configuration afforded the (S)-enantiomer (Table 1,
activity followed the same trend as earlier observed runs 1–15; Table 2, runs 1, 2, 3, 5, 8–11). The same re-
in the alkyl halide alkylation of the same substrate.[25] lationship between the absolute configurations of the
Evidently, the substitution in position three of the sal- catalysts and the products was earlier observed in the
icylaldehyde moiety had a beneficial effect on the alkyl halide alkylation reactions.[25] Evidently, the con-
enantioselectivity of the reaction (compare Table 2, figuration at the a-carbon atom of the products of
run 1 and runs 2, 3). Almost the same effect was other Michael addition experiments, catalysed by L-
brought about by the enlargement of the aromatic
ACHTUNGTREN(NGNU R,R)-1, could also be assigned S. This conclusion is
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Table 2. Conjugate addition of OꢀDonnellꢀs substrate to
methyl acrylate using different catalysts and reaction tem-
peratures.[a]
supported by the DFT calculated stereochemistry of
the transient carbanion/complex cation ion pair (vide
infra).
Further improvement of the asymmetric induction
was achieved by lowering the temperature of the re-
actions, as shown in Table 2 (runs 8–11). The best
temperature was À408C and the enantioselectivity in-
creased to 96% with complex 1b (Table 2, run 11).
The chromium-based catalyst 5 had almost the
same catalytic activity as the corresponding cobalt
complex 1a derived from the same ligand (compare
Table 2, run 1 and run 12).
The scope of the reaction with respect to Michael
acceptors was examined under the optimal conditions
(Table 2, run 11) with 1a and 1b as catalysts. The re-
sults are summarised in Table 3. Remarkably, bulky
tert-butyl acrylate was a poor substrate with the chem-
ical yield and enantiomeric excess of adduct 6b de-
creased (run 2) as compared to methyl acrylate 6a
(run 1).
Run
Catalyst
Temp. [8C]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
L
L
L
N
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0
À13
À40
À40
r.t.
98
97
96
97
95
3
80
95
96
96
97
95
81 (S)
84 (S)
82 (S)
73 (R)
83 (S)
n.d.
14 (S)
84 (S)
86 (S)
88 (S)
96 (S)
78 (S)
DACHTUNGTRENNUNG
LACHTUNGTRENNUNG
L
L
L
L
L
L
N
9[d]
10[d]
11[d]
12
[a]
Reaction conditions: 30 mg (0.101 mmol) OꢀDonnellꢀs
substrate, 10 mol% (0.0101 mmol) catalyst, 1 mL CH2Cl2,
1 equiv. KOH (0.101 mmol) and 3 equiv. methyl acrylate
(0.303 mmol) for 1 hour at different temperatures.
Yield of pure Michael adduct after purification by flash
silica gel chromatography.
Enantiomeric purity was established by CSP HPLC anal-
ysis.
2 h.
[b]
[c]
[d]
Methyl methacrylate could also be involved in the
reaction sequence (Table 3, run 3). The reaction was
slow and had to be conducted at room temperature,
producing the 1,4-adduct 6c in good chemical yield,
low diastereoselectivity and moderate enantioselectiv-
ity (72%) of the major diastereomer.
Table 3. The results of enantioselective conjugate addition of OꢀDonnellꢀs substrate to activated C=C bonds (Scheme 1 and
Scheme 2) promoted by L(R,R)-1a or L
(R,R)-1b.[a]
A
ACHTUNGTRENNUNG
run 1: 6a;[b] c.y. 97%; ee 96% (S)
run 2: 6b;[c,d] c.y. 70%; ee 67% (S)
run 5: 6e;[b,e] c.y. 90%; ee 75% (S)
run 3: 6c;[c,d] c.y. 85%; dr 1.2:1; ee 72% (S)
run 4: 6d;[c,f] c.y. 97%; one syn-
isomer; ee 95% (2S,3S)
run 6: 6f;[b] c.y. 96%; ee 91% (S)
run 7: 6g;[c,f,g] c.y. 96%; one syn-
isomer; ee 70% (2S,3R)
run 8: 6h;[c,d,h] c.y. 84%; dr 2:1; ee 60% run 9: 6i;[c,d,h] c.y. 83%; dr 1.1:1:0.06; ee 70/24/
(configuration n.d.) rac (configuration n.d.)
[a]
Isolated yield, the experimental conditions were those of run 11, Table 2, unless indicated otherwise. Diastereoselectivity
was determined by H NMR of the crude adducts. Enantiomeric purity was determined by CSP HPLC analysis; c.y.=
1
chemical yield, .d.=not determined.
[b]
[c]
[d]
[e]
[f]
L
ACHTUNGTRENNUNG
L
ACHTUNGTRENNUNG
Conducted at room temperature.
1% aqueous KOH was used and the reaction was run at 08C.
Single diastereoisomer was obtained.
1.02 equiv. chalcone were used.
[g]
[h]
2 equiv. of Michael acceptor were used.
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Chiral Octahedral Complexes of CobaltACTHNUTRGENUGN(III) as “Organic Catalysts in Disguise”
ucts in the case of the same substrate addition to b-
substituted acrylic acid derivatives catalysed by chiral
Ca-complexes.[5] Scheme 3 illustrates the assumed
mechanism attributed to our case. The first stage is
the reversible formation of a substrate-catalyst com-
plex stabilised by an array of hydrogen bonds. The
CH-acidity of the substrate is increased and the next
step involves its deprotonation by the base (hydroxide
ion in this case). At this stage any discussion of
a PTC mechanism is unwarranted. This step is fol-
lowed by 1,4-addition of the resulting chiral ion pair
Scheme 2. Preparation of (2S,3S)-3-trifluoromethylpyroglu-
tamic acid from 6d.
On the other hand ethyl (E)-4,4,4-trifluorobute- to acrylonitrile. The intermediate g-carbanion can
noate entered the addition reaction readily, furnishing either undergo cyclization via the intramolecular
a single syn-diastereoisomer of 6d with 95% enantio- Mannich reaction, or be directly protonated. General-
meric excess. The absolute configuration of the ste- ly, this mechanistic consideration can be applied to all
reogenic centers (2S,3S) in 6d was determined by other activated olefins. The ratios of the rates of the
comparison with the literature data on isolated tri- two routes determine which product is formed pref-
fluoromethylpyroglutamic acid as shown in Scheme 2 erably. The use of diluted KOH instead of solid KOH
(see also the Supporting Information).[29] This acid predictably increased the extent of 1,4-addition rela-
was reported to be an important building block for tive to [3+2]-type of reaction and at 08C the ratio
the synthesis of a family of modified calcium-depen- was >20/1. The enantiomeric excess of the major
dent antibiotics (CDAs).[30] There are only three re- product was 75% (Table 3, run 5).
ports in the literature on the synthesis of trifluorome-
a-Enones are favorite electrophiles in asymmetric
thylpyroglutamic acid derivatives[29,31,32] and in all catalytic Michael additions of OꢀDonnellꢀs substrate
cases the acid was obtained as a mixture of all four catalyzed by chiral catalysts.[17,18,33,34] These reactions
possible stereoisomers.
were also effectively promoted by LACTHNGUTERN(UNG R,R)-1a, as sum-
The use of acrylonitrile at room temperature led to marized in Table 3 (runs 6–8). The addition to methyl
the formation of two products, the expected straight vinyl ketone proceeded smoothly and furnished (S)-6f
chain adduct (1,4-addition) and the product of in good chemical yield and with an enantiomeric
[3+2]cycloaddition in
a
ratio 1.7:1 (Table 3, excess of 91% (Table 3, run 6). The addition to chal-
Scheme 3). The formation of the cyclic adducts can be cone was also easy and afforded a single syn-diaste-
rationalised in the same manner as earlier suggested reoisomer (2S,3R)-6g with a moderate enantiomeric
by S. Kobayashi to explain some 3+2 reaction prod- excess of 70% (Table 3, run 7). The configuration of
Scheme 3. Asymmetric addition of OꢀDonnellꢀs substrate to acrylonitrile.
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Victor I. Maleev et al.
Figure 3. Optimized structures of the ion pairs formed between the Z- (left structure) or E-(right structure) OꢀDonnellꢀs eno-
lates and LACHTUNGTRENNUNG(R,R)-1d. Only hydrogen atoms involved in interactions between the species are shown. The assignment of Z and
E was done according to OꢀDonnell.[36]
(2S,3R)-6g was established by comparison with litera- design of APTC catalysts was elaborated by S. Den-
ture data.[17] Cyclohexenone was slow to react and the mark.[35] It is the attack of an electrophile on the less
addition had to be carried out at 08C to give a mixture shielded face of the enolate that determines the even-
of diastereoisomers in a ratio of 2:1 with 60% enan- tual configuration of the product. The bottom face of
tiomeric excess for the major diastereomer (Table 3, the Schiff bases in the complexes (Figure 2) is shield-
run 8). Another substrate, 1-nitro-1-cyclohexene, was ed by the negatively charged phenol oxygen atoms of
also slow to react and only after 26 h was the adduct the second ligand and the substituents of the salicylal-
6i (run 9) obtained with good yield (80%) but low dehyde moieties. At the same time, the upper face of
diastereoselectivity. The ratio of three diastereoiso- the Schiff base plane contains the partially positively
mers was 1.1:1:0.06 according to NMR and their charged amino group of the second ligand. The for-
enantiomeric excesses were estimated as 70/24/0, re- mation of hydrogen bonds between those NH groups
spectively. The absolute configuration of the second and the carbonyl oxygen of the Z-enolate would con-
largest isomer was established by single crystal X-ray strain the orientation of the enolate. The formation of
structure analysis (see Supporting Material). Nitro- strong hydrogen bonds between anions and NH
styrene was unreactive under the routine conditions. groups of our complexes were earlier clearly estab-
Ethyl (E)-but-2-enoate was a very slow reacting sub- lished by X-ray crystal structure analysis.[25]
strate. Crotonaldehyde readily entered the reaction
This hypothesis was supported by DFT quantum
and 3-methyl-substituted proline could be recovered chemical calculations of the ion pairs shown in
from the reaction mixture after reduction with Figure 3. To suggest a plausible structure of the ion
NaBH3CN followed by acidic hydrolysis, but the inter- pair intermediate we performed a series of ab-initio
mediate adduct was highly unstable and the experi- calculations with different dispositions of the cation
ments were poorly reproducible.
complex and carbanion. In all optimized geometries
The transition state of the addition, according to the structure is stabilized by hydrogen bonding of the
the generally held view,[16,35,36] should represent the oxygen atoms of anion and hydrogen atoms of the
À
C C bond formation between an electrophile and the amino groups of the cation. In the case of both Z-
corresponding ion pair formed by the enolate and the and E-enolates, the most stable configuration contains
À
chiral positively charged catalyst (in our case C2-sym- strong bifurcate N H···O hydrogen bonds (N···O dis-
metric chiral complexes). An approach to the rational tances of 2.74–2.81 ꢂ), and it seems that the forma-
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Chiral Octahedral Complexes of CobaltACTHNUTRGENUGN(III) as “Organic Catalysts in Disguise”
under an argon flow. Stainless steel syringes were used to
transfer air- and moisture-sensitive liquids. Components
were visualized using UV light, ninhydrin and/or KMnO4
staining.
tion of these bonds is essential for the intermediate
stabilization. The structure of the most stable Z-form
of the intermediate is additionally stabilized by eight
À
À
À
weaker N H···N, C H···O and C H···p contacts
(Figure 3). The bonding nature of the contacts was re-
vealed in terms of Baderꢀs “atoms in molecules”
theory.[37] The most stable conformation of the inter-
mediate was the Z-enolate (by 9.2 kcalmolÀ1 in
energy, taking into account the energy difference of
0.5 kcalmolÀ1 between E- and Z-forms, Z- being more
stable). In the E-intermediate, the additional bonding
Materials
Commercial reagents were used as received unless stated
otherwise. Column chromatography was performed using
Silica Gel Kieselgel 60 (Merck) and Sephadex LH-20 (Su-
pelco). Potassium hydroxide of 99.99% purity (Sigma–Al-
drich) was used.
À
contacts were weaker C H···O and H···H ones. All
other tested initial configurations either converged to
the latter two or were more than 10 kcalmolÀ1 less
stable that those two.
Instrumentation
Proton nuclear magnetic resonance (1H NMR) spectra,
carbon nuclear magnetic resonance (13C NMR) and fluorine
nuclear magnetic resonance (19F NMR) spectra were record-
ed on a Bruker Avance 300 and Bruker Avance III-400 (op-
erating at 300/75, 400/100 MHz and 282 MHz, respectively)
NMR spectrometer. Chemical shifts (on the d scale) are re-
ported in ppm relative to the residual solvent peak (CHCl3:
d=7.26 ppm for 1H NMR, d=77.16 for 13C NMR, CFCl3:
d=0.0 ppm for 19F NMR). NMR data are reported as fol-
lows: chemical shift, multiplicity (br=broad, s=singlet, d=
doublet, t=triplet, q=quartet, m=multiplet), coupling con-
stant, integration, nucleus. Optical rotations were measured
on a Perkin–Elmer 341 polarimeter in a 5 cm cell. Melting
points were determined in open capillary tubes and are un-
corrected. Enantiomeric excesses were determined by
HPLC analysis using a Shimadzu LC-10 ADVP equipped
with a Shimadzu SPD-M10AVP diode array detector and
column Kromasil 3-AmyCoat, eluent: hexane:2-propanol
(95/5) or (98/2), or with a gas chromatograph (model 3700–
00) equipped with a flame ionisation detector on a DP-
TFA-r-cD chiral stationary phase (32 m ø 0.20 mm). Race-
mic products for reference purposes were synthesised using
achiral catalysts. High-resolution mass spectra were record-
ed at INEOS Mass Spectrometry Service Unit using the ESI
ionisation method.
In the structure of the most stable intermediate, the
disposition of the enolate is asymmetric relative to
the cation. Supposedly, the preferable direction of the
electrophilic attack comes from the exposed “front”
si-side as depicted in Figure 3. The re-side is shielded
because of the hindering disposition of the cyclohex-
ane hydrogen atoms of the neighboring ligand. It is
À
manifested, for example, by the presence of a C H···p
bond critical point between one of those atoms and
the carbonyl group. The electrostatic potential is sig-
nificantly greater (À29.7 vs. À23.3 kcalmolÀ1) on the
exposed side of the enolate (Figure 3, left) than on its
shielded side.
The experimental data fully support this hypothesis
as both alkyl halide alkylation[25] and Michael addi-
tion catalysed by LACHTNUGRTENUNG(R,R)-1d furnished amino acids of
S-configuration (Table 2).
Conclusions
Asymmetric Michael addition of many activated ole-
fins to OꢀDonnellꢀs substrate can be effectively pro-
moted by simple and cheap chiral complexes of
Michael Addition of Glycine tert-Butyl Ester
Benzophenone Schiff Base to Methyl Acrylate:
General Procedure
cobaltACHTUNGTRENNUNG(III) and chromiumACHTUNGTERN(NUGN III) easily prepared in
a two-stage procedure. The range of olefins that could
be involved in the addition reaction is broad and the
stereochemical mechanism of the addition is concep-
tionally very simple. Work is ongoing to further
modify the complexes and explore their applications
in other areas of organic catalysis and anion coordina-
tion applications.
To a mixture of tert-butyl glycinate benzophenone imine
(30 mg, 0.101 mmol), 1b (7.6 mg, 0.0101 mmol) and base
(1 equiv., 0.101 mmol or 3 equiv., 0.303 mmol) in CH2C12
(1 mL) was added methyl acrylate (0.03 mL, 0.323 mmol) at
room temperature. The resulting reaction mixture was
stirred vigorously for 1 or 2 h at room temperature. Purifica-
tion of the reaction mixture by flash chromatography on
silica (diethyl ether) afforded the desired product as a col-
ourless oil. The enantioselectivity was determined by chiral
HPLC analysis of the adduct. The absolute configuration
was determined by hydrolysis of the imine and ester groups
(refluxing 6N HCI, 12 h) and then the residual Glu hydro-
chloride was converted first into the isopropyl ester and
then into the N-trifluoroacyl derivative. The enantiomeric
purity of the compound was determined by GC analysis and
the relative peak retention times were compared with the
literature data.
Experimental Section
General Remarks
When the use of dry solvents is mentioned, the reactions
were conducted under an argon atmosphere. In these cases
the flasks were evacuated while being heated with a heat
gun. The flasks were then cooled to room temperature
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ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Victor I. Maleev et al.
CCDC 978759 contains the supplementary crystallograph-
ic compound 6i. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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Acknowledgements
The authors gratefully acknowledge the financial support
from a joint RFBR and Royal Society, research grant No. 13-
03-92601-KO-a, RFBR research grant No 14-03-31262
young a, RFBR research grant No. 13-03-90600-ARM-a and
a P-8 Russian Academy Presidium grant. The authors are
also grateful to Dr. Michail M. Il’yin for HPLC analysis and
to Dr. Nikolai S. Ikonnikov for GC analysis. I.V.F. made the
DFT calculations on the structure of the chiral ion pair.
A.F.S. solved the X-ray structure of one of the diastereoiso-
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8
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Chiral Octahedral Complexes of Cobalt
G
9
Catalysts in Disguise” for the Asymmetric Addition of
a Glycine Schiff Base Ester to Activated Olefins
Adv. Synth. Catal. 2014, 356, 1 – 9
Victor I. Ma, Michael North, Vladimir A. Larionov,
Ivan V. Fedyanin, Tatyana F. Savel’yeva,
Margarita A. Moscalenko, Alexander F. Smolyakov,
Yuri N. Belokon*
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!