Stable chiral complexes of ionic liquids with Aluminium and biaryl ligands as efficient catalysts for the synthesis of chiral lactones

Article abstract of DOI:10.1055/s-0033-1340518

A new catalytic system for the asymmetric Baeyer-?Villiger oxidation of monosubstituted prochiral cyclobutanones to γ-butyrolactones with high yields (40-99%) and enantioselectivities (45-87%) is described. Aluminium complexes with biaryl ligands and ioni

Full text of DOI:10.1055/s-0033-1340518

LETTER
▌559
lSetttear ble Chiral Complexes of Ionic Liquids with Aluminium and Biaryl Ligands
as Efficient Catalysts for the Synthesis of Chiral Lactones
Chiral Aluminium Complexes for the Synthesis of Chiral Lactones
Agnieszka Drożdż, Magdalena B. Foreiter, Anna Chrobok*
Silesian University of Technology, Faculty of Chemistry, Department of Chemical Organic Technology and Petrochemistry, ul. Krzywoustego
4, Gliwice 44-100, Poland
Fax +48(32)2371032; E-mail: anna.chrobok@polsl.pl
Received: 27.10.2013; Accepted after revision: 09.12.2013
The last two decades have been filled with studies con-
Abstract: A new catalytic system for the asymmetric Baeyer–
cerning the synthesis and applications of ionic liquids.9
Our previous work demonstrated that the use of ionic liq-
Villiger oxidation of monosubstituted prochiral cyclobutanones to
γ-butyrolactones with high yields (40–99%) and enantioselectivi-
ties (45–87%) is described. Aluminium complexes with biaryl li-
uids in the Baeyer–Villiger oxidation resulted in im-
gands and ionic liquids are presented. The incorporation of an ionic proved yields and enhanced reaction rates.10 Among ionic
liquid in the complex structure was confirmed by the observed four-
liquids, chiral analogues are known, bearing the chirality
in the cation or anion.11 Thus far, chiral ionic liquids have
coordinate nature of the aluminium.
Key words: ionic liquids, lactones, biaryl ligands, aluminium com-
plexes, asymmetric catalysis
been used as solvents and organocatalysts for the asym-
metric induction of many types of reactions: Michael ad-
dition, aldol, Baylis–Hillman and Diels–Alder reaction.
Herein, we present a new catalytic system for the asym-
metric Baeyer–Villiger oxidation of monosubstituted pro-
chiral cyclobutanones with cumyl hydroperoxide (CHP)
as the oxidant. To the best of our knowledge, this is the
first example of the application of ionic liquids in an
asymmetric Baeyer–Villiger reaction.
The Baeyer–Villiger (BV) reaction is based on the forma-
tion of esters and lactones by the oxidation of ketones with
peroxide derivatives.1 Of particular importance are new
protocols for the asymmetric version of this reaction for
the synthesis of chiral lactones. γ-Butyrolactones are a
class of chiral compounds that often occur in an enantio-
merically pure form in nature, e.g., Japanese beetle pher-
omone. Furthermore, the γ-butyrolactone subunit is a
valuable building block for the natural synthesis of bio-
logically important substances, such as alkaloids, macro-
cyclic antibiotics, lignan lactones and antileukemics.2
Our idea relies on the introduction of ionic liquids (ILs)
into the structure of an aluminium complex with biaryl li-
gands, as presented in Scheme 1. For this purpose, new
catalytic complexes were synthesised (Table 1). We chose
two ligands: BINOL and the vaulted biaryl ligand
VANOL and Me2AlCl was used as the aluminium precur-
sor. For the ionic liquids, a chiral cation {1-[(1′R,2′S,5′R)-
(–)-menthoxymethyl]-3-methylimidazolium, (–)[mmmim],
or 1-[(1′S,2′R,5′S)-(+)-menthoxymethyl]-3-methylimid-
azolium, (+)-[mmmim]} and an achiral cation (1-butyl-3-
methylimidazolium, [bmim]) were selected, possessing
strongly coordinating anions (Cl–) and weakly coordinat-
ing bis(trifluoromethylsulfonyl)imide ([NTf2]) anions.
The first reports concerning asymmetric BV reactions ca-
talysed by metal complexes date back to 1994. Since then,
syntheses of chiral lactones using chiral catalysts and chi-
ral hydroperoxides have been described.3 One of these
methods uses metal complexes with chiral ligands.
Strukul4 and Bolm5 described the first examples of the ra-
cemic resolution of cyclic alkanones catalysed by plati-
num or copper compounds, obtaining the corresponding
lactones with high ee (up to 69%). Another example of the
synthesis of chiral lactones is the application of titanium
Sharpless catalysts for the oxidation of prochiral cyclobu-
tanones reported by Lopp.6 Other metals (Cu, Zr, Hf, Pt,
Sn, Zn) and their chiral complexes are known to catalyse
the synthesis of lactones with high enantioselectivities (up
to 87% ee).7 One of the most efficient metals for the asym-
metric BV oxidation is aluminium.8 Complexes of this
metal with different chiral ligands, e.g., based on BINOL
(1,1′-bi-2-naphthol) or VANOL (3,3′-diphenyl-2,2′-bi-1-
naphthol), facilitate the synthesis of monosubstituted γ-
butyrolactones from prochiral cyclobutanones with high
enantioselectivity (77–83%).8
The synthesis of the complexes was based on the combi-
nation of equimolar amounts of Me2AlCl with enantio-
pure BINOL or VANOL under a dry, inert atmosphere at
–15 °C in anhydrous dichloromethane followed by the ad-
dition of equimolar amounts of ionic liquid.12
Me2AlCl
Me
OH
OH
O
O
Al
X
ionic liquid
[cation]X
[cation]
Scheme 1 The proposed structures of the biaryl ligand–aluminium
promoter–IL complexes
SYNLETT 2014, 25, 0559–0563
Advanced online publication: 13.01.2014
DOI: 10.1055/s-0033-1340518; Art ID: ST-2013-D0999-L
© Georg Thieme Verlag Stuttgart · New York
1
The complexes were characterised by H NMR, 13C
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
NMR, and 27Al NMR spectroscopy and mass spectrome-

560
A. Drożdż et al.
LETTER
try (Supporting Information). In the organoaluminium 3-substituted cyclobutanones.8 As a model reaction, the
compounds, the chemical shift δ (27Al) is an indicator of oxidation of 3-phenylcyclobutanone with CHP was per-
the coordination number of the aluminium atom. A lone formed with complexes I–IV (molar ratio of complex to
signal was observed in the solid-state 27Al NMR spectra of ketone 0.5) and an ionic liquid as the solvent (Table 2).
the complexes I–IV, with a chemical shift of approxi- The highest enantioselectivity of 3-phenyl-γ-butyrolac-
mately 60–90 ppm. No signals generated by three-fold co- tone was achieved in the reaction with the application of
ordinated aluminium atoms (280–210 ppm) were seen. complex II and [bmim][NTf2] as a solvent (74% ee; Table
This fact confirms the change of the coordination number 2, entry 1). Acceptable enantioselectivity of 67% ee was
for aluminium from three to four and the incorporation of also achieved using complex III with BINOL ligand and
the ionic liquid into the complex structure. The structures [bmim][NTf2] as a solvent (Table 2, entry 2). Unfortu-
of all the complexes synthesised were also confirmed by nately, the replacement of the [bmim] cation in complex
electrospray ionisation mass spectrometry (ESI–MS). In III with chiral [(+)mmmim] cation and the application of
the positive ESI (+) mode m/z signals belonging to this new complex I with chiral ionic liquid as a solvent
[bmim]/[mmmim] cations were found. Similarly, in the caused a drop in the enantioselectivity of the product to
negative ESI (–) mode, signals belonging to the anionic 52% ee (Table 2, entry 3). Complex IV, with the strongly
fragments were identified (Supporting Information).
coordinating anion [Cl–], had a detrimental effect on the
catalysis, leading to a racemic product and lower yields.
The results clearly demonstrate that the main influence on
the study of asymmetric Baeyer–Villiger reaction is the
structure of biaryl ligand and the solvent.
All the synthesised complexes were tested as catalysts for
the asymmetric Baeyer–Villiger reaction (Scheme 2). We
used the optimal reaction conditions reported in the liter-
ature for the aluminium-catalysed oxidation of prochiral
Table 1 Synthesis of the Complexes from Me2AlCl (1 mmol), Biaryl Ligand (1 mmol) and IL (1 mmol) at –15 °C in Dichloromethane
Ionic liquid/ligand
Complex
Yield (%)
N
Me
N
O
O
Me
(+)[mmmim][NTf2]/(R)-BINOL
99
Al
O
NTf2
I
Me
Ph
Ph
O
Al
O
[bmim][NTf2]/(R)-VANOL
95
NTf2
N
Me
N
II
O
Me
Al
O
[bmim][NTf2]/(R)-BINOL
90
N
NTf2
N
Me
III
O
O
Me
Cl
Al
[bmim][Cl]/(R)-BINOL
Synlett 2014, 25, 559–563
95
N
N
Me
IV
© Georg Thieme Verlag Stuttgart · New York

LETTER
Chiral Aluminium Complexes for the Synthesis of Chiral Lactones
561
the reaction has an influence on the enantioselectivity.13
Based on the results from Table 2 [mmmim][NTf2] and
[bmim][NTf2] were used as solvents. The molar ratio of
the complex/ketone was recalculated with the assumption
that the complex is created from an equimolar ratio of bi-
aryl ligand/MeAlCl2/IL. Increasing the complex/ketone
molar ratio from 0.1 to 0.5 and the concentration of ke-
tone, resulted in a high yield and relatively high ee values
(Table 3, entries 1 and 2). Different combinations of chiral
IL (+)/(–) [mmmim][NTf2] with (R)-BINOL or (R)-
VANOL did not influence the ee value (Table 3, entries 2,
3 and 7). However, (S)-BINOL had a detrimental effect on
the ee value (Table 3, entry 4). The best results, full con-
version of the ketone and high ee, were obtained using
[bmim][NTf2] with (R)-VANOL (ee 87%, Table 3, entry
6) and [bmim][NTf2] with (R)-BINOL (ee 75%, Table 3,
entry 5). These results are comparable to those found
in the literature.8 Among the organoanions, acetate
and lactate were also examined with [bmim] and
(+)/(–)[mmmim] cations. These anions possess slightly
different properties to those of the [NTf2] anion. They are
basic, capable of hydrogen bonding, and are strongly co-
ordinating towards metal ions (Table 3, entry 8). The low
activity of these complexes caused racemic mixtures and
low yields of lactone. Tests for recycling the catalytic
phase were performed in the same manner as presented in
Table 2 (without any addition of fresh Me2AlCl) and
showed a relatively small decrease in ee and lower yields
(Table 3, entry 5a and 6a). To show the stability of the
new aluminium complexes, the 27Al NMR spectroscopy
of the catalytic phase used for the second cycle was per-
formed. The presence of a signal from aluminium with a
coordination number of four was found which confirmed
the presence of the active complex in the recycled mix-
ture.
O
I–IV, IL
O
CHP (3 equiv), –25 °C to r.t.
O
Scheme 2 Oxidation of 3-phenylcyclobutanone to 3-phenyl-γ-buty-
rolactone
Table 2 Oxidation of 3-Phenylcyclobutanone (0.5 mmol) to 3-Phe-
nyl-γ-butyrolactone with CHP (1.5 mmol) in the Presence of Com-
plexes I–IV (0.25 mmol) and Ionic Liquid (0.8 g) at –25 °C to Room
Temperature
Entry Complex
IL (solvent)
Yield (%)a ee (R) (%)
1
II
[bmim][NTf2]
II (recycle) [bmim][NTf2]
99
50
74
57
1a
2
3
4
III
I
[bmim][NTf2]
[(+)mmmim][NTf2]
[bmim][Cl]
89
99
70
67
52
0
IV
a Determined by GC.
We next tested the reusability of the aluminium complex-
es in the standard reaction with complex II to check
whether the complex was still active after the reaction cy-
cle. To this aim, the post-reaction mixture was extracted
with dibutyl ether to isolate the product, unreacted CHP
and other by-products. After evaporation of the dibutyl
ether, the ionic liquid with the immobilised complex (cat-
alytic phase) was used in another reaction cycle without
any addition of fresh portion of complex II or Me2AlCl
(Table 2, entry 3). Unfortunately, we observed a decrease
in the enantioselectivity and yield of the product indicat-
ing that the complex had partially lost activity.
To improve these promising results further, we decided to
create the complex in situ. The order of reagents, the
quantity of reagents and the temperature of each step of
Table 3 Oxidation of 3-Phenylcyclobutanone (0.5 mmol) to 3-Phenyl-γ-butyrolactone with CHP (1.5 mmol) in the Presence of Me2AlCl (0.25
mmol), Biaryl Ligand (0.25 mmol) and Ionic Liquid (0.8 g) at –25 °C to Room Temperature (Reaction Time: 22 h)
Entry
Biaryl ligand
Ionic liquid
xa
Yield (%)b
ee (%)b
1
2
3
4
(R)-BINOL
(R)-BINOL
(R)-BINOL
(S)-BINOL
(R)-BINOL
1.6 g (+) [mmmim][NTf2]
0.8 g (+) [mmmim][NTf2]
0.8 g (–) [mmmim][NTf2]
0.8 g (+) [mmmim][NTf2]
0.8 g [bmim][NTf2]
0.1
0.5
0.5
0.5
0.5
66
98
98
98
98
45 (R)
68 (R)
69 (R)
57 (S)
75 (R)
5
5a
65 (recycle) 59 (R)
6
(R)-VANOL
0.8 g [bmim][NTf2]
0.5
98 87 (R)
6a
50 (recycle) 77 (R)
7
8
(R)-VANOL
(R)-BINOL
0.8 g (+) [mmmim][NTf2]
0.5
0.5
98
68 (R)
0.8 g [bmim][OAc] or [bmim][lactate] or (+)/(–) [mmmim][lactate]
<60
0
a Molar ratio of complex/ketone calculated with the assumption that the complex is created in situ with an equimolar ratio of biaryl ligand–
MeAlCl2–ionic liquid.
b Determined by GC with a precision of ±1%.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 559–563

562
A. Drożdż et al.
LETTER
Next, the optimal conditions with the (R)-BINOL ligand, of the cyclobutanone with electron-withdrawing group
[bmim][NTf2] ionic liquid, Me2AlCl as aluminium source showed reduction in enantioselectivity. Neither the intro-
and cumyl hydroperoxide as oxidant were examined in the duction of chlorine atom in para position of the phenyl
BV oxidation of various 3-substituted cyclobutanones to ring nor the replacement of a phenyl group with an alkyl
determine its scope (Table 4). Cyclobutanones used in this group at C-3 position had a detrimental effect (45% and
study were synthesised by means of a [2+2]-cycloaddition 48% ee respectively, Table 4, entries 3 and 5). A good lev-
of dichloroketene and an olefin, followed by subsequent el of enantioselectivity was achieved in the oxidation of p-
dehalogenation.14
methoxyphenylcyclobutanone (62% ee, Table 4, entry 4),
while a cyclobutanone bearing the chlorine substituent in
C-2 position provided a high enantioselection (86% ee,
Table 4, entry 4).
Table 4 Oxidation of 3-Substituted Cyclobutanone (0.5 mmol) to 3-
Substituted γ-Butyrolactone with CHP (1.5 mmol) in the Presence of
Me2AlCl (0.25 mmol), (R)-BINOL (0.25 mmol) and [bmim][NTf2]
(0.8 g) at –25 °C to Room Temperature
Finally, it is worth noting that imidazolium-based ionic
liquids can interact by various means, e.g. electrostatic in-
teractions, π–π stacking, hydrogen bond donation, and the
formation of hydrophobic (possible Van der Waals inter-
actions) and hydrophilic domains. Anions of ionic liquids
also play important roles as hydrogen-bond acceptors or
Lewis bases. Several ionic liquids applied for the creation
of chiral complexes of biaryl ligand with aluminium pre-
sented in this work, possessing anions such as lactate, ac-
etate or chloride had a detrimental effect on the catalysis.
These anions are strongly coordinating towards metal
ions. Based on this observation it can be proposed that
Lewis acidity of the aluminium atom is important for this
transformation. Presumably, the more acidic the metal,
the lower the activity of the complex in the BV reaction.
A similar effect was observed by Bolm8a when investigat-
ing the relationship between the electronic properties of
the biaryl ligand and the enantioselectivity of the BV re-
action.
Entry Ketone
Lactone
Yield ee (R)
(%)
(%)
O
O
O
O
1
99a
75a
O
O
2
99b
86b
Cl
Cl
.
O
O
O
The mechanism of the BV reaction in the presence of
complexes reported in this work probably involves initial
formation of the chiral complex, for example of type III,
and then coordination of the ketone and cumyl hydroper-
oxide to the aluminium atom (Figure 1, structure A). The
next step involves Criegee intermediate formation (Figure
1, structure B), which then stereoselectively rearranges to
the lactone. Probably, if the Lewis acidity of the alumini-
um atom is too high, the rearrangement step is hindered.
3
40b
45b
Cl
Cl
.
O
.
O
O
4
70b
62b
A
R3
MeO
MeO
H
O
.
O
O
.
O
O
O
Me
NTf2
Al
O
5
99a
48a
O
N
n-Bu
R1
R2
n-Bu
N
Me
a Yields were determined by GC; enantioselectivities were deter-
B
mined chiral GC.
b Yields and enantioselectivities after 22 h were determined by chiral
HPLC.
R3
H
R1
O
O
O
O
Al
Me
R2
In practical terms, 3-substituted cyclobutanones were
readily oxidised to their corresponding lactones in high
yields (40–99%) and enantioselectivities (54–75%). Vari-
ation of the substitution pattern in the phenyl substituent
O
N
NTf2
Me
N
Figure 1 Postulated chiral intermediates
Synlett 2014, 25, 559–563
© Georg Thieme Verlag Stuttgart · New York

LETTER
Chiral Aluminium Complexes for the Synthesis of Chiral Lactones
563
Chem. 2001, 79, 1593. (c) Bolm, C.; Beckmann, O.; Kühn,
T.; Palazzi, C.; Adam, W.; Rao, P. B.; Saha-Möller, C. R.
Tetrahedron: Asymmetry 2001, 12, 2441. (d) Bolm, C.;
Frison, J.; Zhang, Y.; Wulff, W. D. Synlett 2004, 1619.
(9) (a) Olivier-Bourbigou, H.; Magna, L.; Morvan, D. Appl.
Catal. A 2010, 373, 1. (b) Betz, D.; Altmann, P.; Cokoja, M.;
Herrmann, W. A.; Kuhn, F. E. Coord. Chem. Rev. 2011, 255,
1518.
(10) (a) Baj, S.; Słupska, R.; Chrobok, A.; Drożdż, A. J. Mol.
Catal. A 2013, 376, 120. (b) Chrobok, A. Tetrahedron 2010,
66, 2940. (c) Chrobok, A. Tetrahedron 2010, 66, 6212.
(d) Baj, S.; Chrobok, A.; Słupska, R. Green Chem. 2009, 11,
279. (e) Chrobok, A.; Baj, S.; Pudło, W.; Jarzębski, A. Appl.
Catal. A 2009, 366, 22.
(11) Payagala, T.; Armstrong, D. W. Chirality 2012, 24, 17.
(12) Synthesis of the Complexes I–IV: Me2AlCl (1 mmol),
biaryl ligand (1 mmol), ionic liquid (1 mmol) and anhyd
CH2Cl2 (1 mL) were placed in a round-bottom flask under a
dry, inert atmosphere at –15 °C. The contents of the flask
were stirred for 1 h. After this time, evaporation of the
solvent gave complexes I–IV in high yields (90–99%).
Complex II: 1H NMR (600 MHz, DMSO): δ = 0.89 (t, J =
8.5 Hz, 3 H), 1.25 (sextet, J = 8.2 Hz, 2 H), 1.75 (p, J = 8.2
Hz, 2 H), 3.85 (s, 3 H), 4.15 (t, J = 8.2 Hz, 2 H), 6.67–6.75
(m, 4 H), 6.80–6.89 (m, 4 H), 6.90–7.02 (m, 2 H), 7.15 (s, 2
H), 7.29–7.35 (m, 1 H), 7.43–7.50 (m, 4 H), 7.61–7.71 (m, 1
H), 7.75–7.81 (m, 2 H), 8.25–8.35 (m, 2 H), 9.05 (s, 3 H,
AlCH3), 9.15 (s, 1 H). 13C NMR (150 MHz, DMSO): δ =
13.22, 18.73, 31.31, 35.70, 48.46, 116.17, 117.25, 119.62 (q,
[(CF3SO2)2N], 122.24, 123.59, 123.91, 124.81, 125.09,
126.05, 126.60, 126.89, 128.70, 133.49, 136.50, 141.13,
141.90, 151.47, 159.57. 27Al NMR (400 MHz): δ = 60.13.
ESI–MS: m/z = 139 ([bmim]+), 437 ([VANOL]–), 280
([(CF3SO2)2N]–).
(13) General Procedure for the Synthesis of 3-Phenyl-γ-
butyrolactones: The sequence of the reagent addition was
as follows: first the ketone (0.5 mmol), then biaryl ligand
(0.25 mmol), followed by the addition of ionic liquid (0.8 g)
were placed in a round-bottom flask under a dry, inert
atmosphere and cooled to –15 °C. After the addition of
Me2AlCl (0.25 mmol), the contents of the flask were stirred
for 1 h. Next, CHP (1.5 mmol) was added at –25 °C and the
reaction was allowed to warm to r.t. and left for 22 h. Yields
and enantioselectivities of lactone were determined by GC.
(14) Krepski, L. R.; Hassner, A. J. Org. Chem. 1978, 43, 2879.
In conclusion, new aluminium complexes with biaryl li-
gands and ionic liquids are presented. The incorporation
of an ionic liquid in the complex structure was confirmed
by observation of the four-coordinate nature of the alu-
minium using 27Al NMR spectroscopy. Subsequently, the
new complexes were used as catalysts for the asymmetric
Baeyer–Villiger oxidation of 3-substituted cyclobuta-
nones. The most effective catalytic system was composed
of (R)-VANOL, Me2AlCl and [bmim][NTf2]. Careful
choice of ionic liquid and reaction conditions allowed the
synthesis of 3-substituted γ-butyrolactones in high yields
and enantioselectivities. Several important parameters
have been studied, and the results of this work have pro-
vided useful insights into understanding how ILs may be
used in the asymmetric BV oxidation. Further studies are
currently under investigation.
Acknowledgment
This work was financed by the Ministry of Science and Higher Edu-
cation (Grant no. N N209 021739).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SuppInigfor
m
o
ti
References and Notes
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