Enantioselective Baeyer-Villiger oxidations catalyzed by chiral magnesium complexes

Article abstract of DOI:10.1055/s-2001-16792

Catalytic enantioselective Baeyer-Villiger oxidations of 3-substituted cyclobutanones with cumene hydroperoxide as oxidant have successfully been performed in the presence of chiral magnesium catalysts. The combination of enantiopure BINOL and a variety o

Full text of DOI:10.1055/s-2001-16792

LETTER
1461
Enantioselective Baeyer-Villiger Oxidations Catalyzed by Chiral Magnesium
Complexes
Carsten Bolm,* Oliver Beckmann, Annabel Cosp, Chiara Palazzi
Institut für Organische Chemie der RWTH Aachen, Professor Pirlet-Str. 1, 52056 Aachen, Germany
Fax +49 241 8888 391; E-mail: Carsten.Bolm@oc.RWTH-Aachen.de
Received 8 June 2001
O
[Mg] (50 mol%),
(R)-BINOL (50 mol%)
O
Abstract: Catalytic enantioselective Baeyer-Villiger oxidations of
3-substituted cyclobutanones with cumene hydroperoxide as oxi-
dant have successfully been performed in the presence of chiral
magnesium catalysts. The combination of enantiopure BINOL and
a variety of Mg reagents is able to promote the oxidation of ketones
with good enantiomeric excesses. MgI2 or MeMgI as metal source
were found to give the best enantioselectivities.
O
CHP (1.5 equiv.),
DCM, –25 °C, 8 h
1
2
Scheme 1
Key words: asymmetric catalysis, Baeyer-Villiger reaction,
BINOL, lactones, magnesium, oxidation
many organomagnesium compounds gave products with
notable enantiomeric excess. The precise nature of the
Mg(II) compound strongly influenced both activity and
enantioselectivity. Among the various reagents surveyed,
MeMgI and MgI2 afforded the best results, i.e., full con-
version and ee values up to 60% and 65%, respectively
(Table 1). However, when magnesium triflate was em-
ployed as precursor, the conversion of 1 to lactone was
only 20% and no asymmetric induction was observed.
With the use of both anhydrous MgCl2 and MgSO4 the ox-
idation was completely inhibited. The superiority of MgI2
may be attributed to the easier dissociation of an iodide
anion from species such as L2MgI2 as already proposed by
Corey et al.3g On the other hand, the counterion may be
fundamental in determining the geometry of the active
complex, as Desimoni had suggested with respect to Mg-
catalyzed dipolar cycloadditions.2c
In recent years, many catalytic reactions have been estab-
lished that involve a Lewis acid as the chiral mediator.1
Among these, the use of magnesium has received much
attention in 1,3-dipolar cycloadditions2 and Diels-Alder
reactions,3 but to the best of our knowledge, only a single
Mg-catalyzed oxidation has been reported,4 to which we
wish to add another example, viz an asymmetric variant of
the Baeyer-Villiger oxidation.
Several metal-catalyzed5 and biocatalytic6 versions of
asymmetric Baeyer-Villiger reactions using racemic or
prochiral ketones for the synthesis of optically active lac-
tones have been developed. Systems that employ Lewis
acids consist, e.g., of copper7 or platinum8 complexes or a
zirconium species,9 which proved able to mediate the ox-
idation of cyclic ketones to enantiomerically enriched lac-
tones. Another variant, which is in some respect the most
efficient one, relies on an aluminum-BINOL catalyst.10
We here present a novel system,11 in which a chiral Mg(II)
species prepared from Grignard reagents as well as from
alkylmagnesium compounds or Mg salts with readily
available enantiopure BINOL serves as an effective Lewis
acid.
Table 1 Asymmetric oxidation of 1 mediated by various Mg
reagents in combination with enantiopure BINOLa
Entry
Conv. (%)b
Ee (%)c
Magnesium source
Bu2Mg
1
2
100
100
33
49
MeMgBr
In our initial evaluation of Mg(II)-based mediators, we
used as the model reaction the oxidation of 3-phenylcy-
clobutanone (1) by cumene hydroperoxide (CHP) in the
presence of a complex derived from MgBu2 and a chiral
chelating ligand.12 Among several ligands tested, only
enantiopure BINOL was successful leading to full conver-
sion of the substrate affording the corresponding lactone
with 33% enantiomeric excess (ee).
PhMgBr
MeMgI
3
4
5
6
7
70
58
61
100 (93)
20
Mg(OTf)2
rac
MgBr2·OEt2
MgI2
80
50
65
100 (91)
This result encouraged us to focus on a screening of dif-
ferent metal sources and to examine their applicability in
the oxygen transfer to prochiral substrates. Interestingly,
and in contrast to what we had noticed in the case of the
aluminum system,10 in which only Me2AlCl was found to
be suitable for the asymmetric Baeyer-Villiger oxidation,
aConditions: [Mg] (50 mol%), (R)-BINOL (50 mol%),
PhC(CH3)2OOH (1.5 equiv.), CH2Cl2, 25 °C, 8 h. Determined by
b
GC. The values in parentheses refer to yields of pure lactone isolated
c
by column chromatography. Determined by GC using chiral co-
lumns.
Synlett 2001, No. 9, 1461–1463 ISSN 0936-5214 © Thieme Stuttgart · New York

1462
C. Bolm et al.
LETTER
As to the solvent, the use of coordinating media such as Attempts to increase the asymmetric induction by modify-
ether led to low conversion. In dichloroethane and chlo- ing the substitution pattern of the BINOL ligand failed.
robenzene, the product had 60% and 55% ee, respectively. For instance a BINOL derivative bearing bromo substitu-
The solvent of choice, however, was dichloromethane, ents in position 3 and 3’ vicinal to the hydroxyl groups in-
which allowed the formation of 2 with 65% ee.
hibited the oxidation of 1 while the same substituent in
position 6 and 6´ caused the ee to decrease to 56%. The
use of mono or diprotected BINOL (methoxy instead of
hydroxy groups) as well as 2,2’-diaminobinaphthyl and
BINAP afforded racemic products. Finally, an oxidation
in the presence of Li di-BINOLate gave 2 with 33% ee.
Table 2 relates the ee values of lactones that were obtained
by complete oxidation of the corresponding prochiral cy-
clobutanones.13 The oxidation of compounds with an
alkyl or a benzyl group in position 3 led to results compa-
rable with the one of 3-phenyl cyclobutanone.
As the use of only 50 mol% of Mg-BINOL was as effec-
tive as the stoichiometric variant of the oxidation a further
reduction of the catalyst loading was tried. Indeed, an ex-
periment with 3-phenyl cyclobutanone (1) as substrate
confirmed that complete conversion and an ee value of
still 63% was attainable by employing only 25 mol% of
the chiral mediator.
Table 2 Mg-catalyzed asymmetric oxidation of various cyclobuta-
nonesa
Ee (%) of
Entry
Config.
Ref.
14a
Substrate
the lactoneb
O
In summary, we have disclosed a novel, main group met-
al-based asymmetric Baeyer-Villiger system that furnish-
es appreciable enantioselectivities at high conversion. In
view of the state of the art in metal-catalyzed Baeyer-Vil-
liger oxidation, these are promising results which prompt
us to continue our investigation.
65
(–)-(R)
1
O
63
52
(–)-(R)
14b
15
2
3
Cl
O
(–)
Acknowledgement
n-Octyl
We are grateful to the DFG (SPP Peroxidchemie / Sauerstoff-
transfer) and the Fonds der Chemischen Industrie for financial sup-
port.
O
64
(–)-(S)
14c
4
References and Notes
O
O
(1) Lewis Acids in Organic Synthesis; Yamamoto, H., Ed.; Wiley-
VCH: Weinheim, 2000.
O
61
56
(–)-(S)
(–)-(S)
14d
14e
5
6
O
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MeO
aConditions: MgI2 (50 mol%), (R)-BINOL (50 mol%), CHP (1.5
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b
columns.
In order to vary the Mg complex further, several additives
were tested. The addition of 1 equivalent of iodine, which
had been shown to be benign for Diels-Alder reactions in-
volving MgI2, due to the dissociation of the iodide as a io-
dinate,3g resulted in a small decrease in enantiomeric
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observations of Jørgensen and Desimoni, who assumed
that molecular sieves represented a necessary part of their
magnesium catalyst system.2a,c DBU and AgSbF6, which
proved advantageous in asymmetric Diels-Alder reac-
tions,3b effected a shutdown of the oxidation reaction.
Only the presence of AgNO3 allowed a slightly higher
enantioselectivity (66% ee).
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Synlett 2001, No. 9, 1461–1463 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Enantioselective Baeyer-Villiger Oxidations Catalyzed by Chiral Magnesium Complexes
1463
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atmosphere at room temperature for 30 minutes. The ketone
(0.2 mmol) was added and the solution cooled down to 25 °C
before the reaction was eventually started by injection of the
hydroperoxide (0.3 mmol). The mixture was allowed to warm
in the cooling bath during 8 h, then quenched with a 0.5 N
solution of aqueous HCl. The organic phase was extracted
with MTBE, and washed with 5 wt% aqueous Na2S2O3, water
and brine. After being dried over MgSO4 the crude products
solution was either directly subjected to GC analysis or
purified by column chromatography to determine the yields.
(13) Prochiral 3-monosubstituted cyclobutanones are accessible by
means of [2+2]-cycloaddition of dichloroketene to an olefin
with subsequent dehalogenation. For syntheses, see:
(a) Ghosez, L.; Montaigne, R.; Roussel, A.; Vanlierde, A.;
Mollet, P. Tetrahedron 1971, 27, 615. (b) Krepski, L. R.;
Hassner, A. J. Org. Chem. 1978, 43, 2879. (c) Kaiwar, V.;
Reese, C. B.; Gray, E. J.; Neidle, S. J. Chem. Soc., Perkin
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(14) The absolute configurations of the products were determined
by comparison of their optical rotation with literature data:
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18, 65. (b) Lawston, J. W.; Inch, T. D., J. Chem. Soc., Perkin
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(15) The absolute configuration of the ( )-octyl-bearing lactone is
supposed to be (S) since (S)-configured 3-pentyl and 3-hexyl
butyrolactones exhibited a negative rotation, too. See: Kosugi,
H.; Tagami, K.; Takashi, A.; Kanna, H.; Uda, H. J. Chem.
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Article Identifier:
1437-2096,E;2001,0,09,1461,1463,ftx,en;G11201ST.pdf
Synlett 2001, No. 9, 1461–1463 ISSN 0936-5214 © Thieme Stuttgart · New York