Novel manganese-catalyzed α-oxidation of cyclic β-keto esters with molecular oxygen

Full text of DOI:10.1021/jo9909094

7668
J . Org. Chem. 1999, 64, 7668-7669
Sch em e 1
Novel Ma n ga n ese-Ca ta lyzed r-Oxid a tion of
Cyclic â-Keto Ester s w ith Molecu la r
Oxygen
J ens Christoffers
Technische Universita¨t Berlin, Institut fu¨r Organische
Chemie, Sekretariat C 3, Strasse des 17. J uni 135,
D-10623 Berlin, Germany
Sch em e 2
Received J une 3, 1999
Oxidation is a common way of functionalizing organic
compounds. In terms of economical and ecological con-
siderations, molecular oxygen is the oxidant of choice.
However, the reaction of O2 with most organic materials
is (fortunately) kinetically hindered1 and must be cata-
lyzed.2 We report on a new chemoselective and regiose-
lective oxidation of cyclic â-keto esters 1 with O2 catalyzed
by Mn(OAc)2‚4H2O yielding the R-hydroxy derivatives 2
(Scheme 1).
Sch em e 3
The R-position of â-dicarbonyl compounds is naturally
nucleophilic, and a number of electrophilic reagents can
be utilized for introduction of an oxygen functionality at
this position. Common examples are Pb(OAc)4,3 MOPH,4
percarboxylic acids,5 dimethyldioxirane,6 or singlet oxy-
gen.7 In the course of our search for a chiral transition-
metal catalyst for asymmetric Michael reactions,8 we
discovered that Mn(OAc)2‚4H2O does catalyze the oxida-
tion of ester 1a , if air was not excluded. Optimization of
this reaction gave a very simple protocol: Stirring of 1a
with 5 mol % Mn(OAc)2‚4 H2O under an atmosphere of
O2 in CH2Cl2 without an additional ligand or any other
additive is sufficient to fully convert the starting material
into product 2a .6 The reaction proceeds at room temper-
ature, and after an induction period of about 1 h the
mixture becomes dark colored and homogeneous, and
within 1 d the conversion is quantitative. Separation of
the product 2a from the catalyst can be achieved by direct
distillation from the reaction mixture under reduced
pressure yielding 85-90% of a material, which contains
only small amounts of 1a and acetic acid as impurities.
Unfortunately, this very simple workup procedure of
1a is an exceptional case. The oxidation of 1b and 1c
proceeds with similar results as 1a , but products 2b9 and
2c are not as stable under reaction conditions as 2a .
Thus, small amounts of decomposition products are
formed that have to be separated by chromatography. To
figure out what kind of subsequent reactions are pro-
ceeding, we have stirred a reaction mixture of 1b for 3 d
at room temperature, after which period chromatographic
workup yielded besides 2b products 3 and 45 (Scheme
2). Formation of 4 can be rationalized by Baeyer-Villiger
oxidation of 2b followed by retro-Claisen C-O bond
cleavage. From a mechanistic point of view, the formation
of compound 3 remains unclear and obscure.10
The mechanism of the conversion from 1 into 2 can be
assumed to be the one-pot analoge to the sequence known
as the Rubottom oxidation:12 epoxidation of the enol
tautomer of 1 by a Mn(V) oxo species13 followed by
rearrangement of the resulting hydroxy oxirane to the
hydroxy ketone.14
Efforts to convert â-diketones or acyclic â-keto esters
under similar or modified conditions as for 1a -c have
not been successful. Only in one case, the conversion of
1d , an oxidation product (compound 5, Scheme 3) was
isolated in 6% yield. The constitution of 5, which was
deduced from a number of double-resonance NMR ex-
periments, obviously supports the proposed mechanism
leading to compounds 2 starting from 1. The relative cis
configuration of 5 was established by NOE between o-H
and 2-H.
In summary, the new manganese-catalyzed oxidation
of cyclic â-keto esters with O2 offers an economically and
* To whom correspondence should be addressed. Fax: +49-30-723
1233. E-mail: jchr@wap0105.chem.tu-berlin.de.
(1) A number of noncatalyzed selective conversions of organic
substrates with oxygen are also known; e.g.: Bailey, E. J .; Barton, D.
H. R.; Elks, J .; Templeton, J . F. J . Chem. Soc. 1962, 1578.
(2) Holm, R. H. Chem. Rev. 1987, 87, 1401.
(3) Schultz, A. G.; Holoboski, M. A. Tetrahedron Lett. 1993, 34, 3021.
(4) MoO5‚pyridine‚HMPA: Vedejs, E.; Engler, D. A.; Telschow, J .
E. J . Org. Chem. 1978, 43, 188.
(5) Hubert, A. J .; Starcher, P. S. J . Chem. Soc. C 1968, 2500.
(6) Adam, W.; Smerz, A. K. Tetrahedron 1996, 52, 5799.
(7) Wasserman, H. H.; Pickett, J . E. Tetrahedron 1985, 41, 2155.
(8) (a) Christoffers, J .; Mann, A.; Pickardt, J . Tetrahedron 1999, 55,
5377. (b) Christoffers, J .; Mann, A. Eur. J . Org. Chem. 1999, 1475, 5.
(c) Christoffers, J .; Ro¨ssler, U. Tetrahedron: Asymmetry 1999, 10, 1207.
(d) Christoffers, J . J . Prakt. Chem. 1999, 341, 495.
(10) Formation of 3 as a byproduct is also observed in nickel,8 cobalt,8
and iron11 catalyzed conversions of oxoester 1b with carbon electro-
philes. Even commercial materials of 1b contain epoxide 3 in quantities
up to 2% in some cases. On the other hand, we never detected the
formation of homologous products from oxo esters 1a or 1c.
(11) (a) Christoffers, J . J . Chem. Soc., Perkin Trans. 1 1997, 3141.
(b) Christoffers, J . Eur. J . Org. Chem. 1998, 1259, 9.
(12) (a) Rubottom, G. M.; Vazquez, M. A.; Pelegrina, D. R. Tetra-
hedron Lett. 1974, 4319. (b) Hassner, A.; Reuss, R. H.; Pinnick, H. W.
J . Org. Chem. 1975, 40, 3427. (c) Brook, A. G.; Macrae, D. M. J .
Organomet. Chem. 1974, 77, C19.
(13) Srinivasan, K.; Michaud, P.; Kochi, J . K. J . Am. Chem. Soc.
1986, 108, 2309.
(9) Crout, D. H. G.; Rathbone, D. L. J . Chem. Soc., Chem. Commun.
1987, 290.
(14) Zhu, Y., Manske, K. J .; Shi, Y. J . Am. Chem. Soc. 1999, 121,
4080.
10.1021/jo9909094 CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/11/1999

Notes
J . Org. Chem., Vol. 64, No. 20, 1999 7669
(vs) cm-1; mol. mass calcd 186.0892, found 186.0987 (HRMS).
Anal. Calcd for C9H14O4 (186.21): C, 58.05; H, 7.58. Found: C,
58.21; H, 7.33.
ecologically friendly way for the chemo- and regioselective
functionalization of compounds 1a -c.
Eth yl 2,3-Ep oxycycloh exa n on e-2-ca r boxyla te (3). The
procedure reported for 2b was repeated on the same scale. After
the reaction mixture was stirred for 3 d at room temperature,
chromatography on SiO2 (PE/MTB 1:1) yielded three fractions:
(1) Rf ) 0.39, compound 2b (273 mg, 1.47 mmol, 25%), (2) Rf )
0.26, compound 3 (487 mg, 2.64 mmol, 45%), and (3) Rf ) 0.05
(PE/MTB 1:1), 0.35 (MTB), compound 4 (273 mg, 1.35 mmol,
23%): 1H NMR (CDCl3, 200 MHz) δ 1.26 (t, J ) 7.2 Hz, 3 H),
1.68-2.10 (m, 3 H), 2.16 (d, J ) 10.7, 6.5 Hz, 1 H), 2.21-2.34
(m, 1 H), 2.51 (dtd, J ) 17.0, 4.3, 0.6 Hz, 1 H), 3.64 (t, J ) 1.9
Hz, 1 H), 4.23 (q, J ) 7.2 Hz, 2 H) ppm; 13C{1H} NMR (CDCl3,
50 MHz) δ 13.91 (CH3), 16.33 (CH2), 22.71 (CH2), 37.21 (CH2),
58.57 (C), 59.82 (CH), 61.93 (CH2), 165.95 (CdO), 199.39 (Cd
O) ppm; IR (ATR) 1/λ 1745 (vs), 1714 (vs) cm-1; mol. mass calcd
184.0736, found 184.0717 (HRMS). Anal. Calcd for C9H12O4
(184.19): C, 58.69; H, 6.57. Found: C, 58.22; H, 6.54.
Exp er im en ta l Section
Gen er a l Meth od s. Column chromatography was accom-
plished with Merck silica gel (type 60, 0.063-0.200 mm) using
tert-butyl methyl ether (MTB) and hexanes (PE). Multiplicity
assignments of 13C NMR resonances were made using DEPT
experiments. All starting materials were commercially available.
Eth yl 2-Hyd r oxycyclop en ta n on e-2-ca r boxyla te (2a ). Ox-
oester 1a (1.00 g, 6.40 mol) was added to a suspension of Mn-
(OAc)2‚4H2O (78 mg, 0.32 mmol) in CH2Cl2 (1 mL). The mixture
was cooled with N2(l), the flask was evacuated and equipped with
a balloon of O2 (ca. 500 mL, ca. 22 mmol), and finally the mixture
was stirred for 14 h at room temperature. The solvent was
removed in vacuo and the residue distilled in a Kugelrohr
apparatus (1 mbar, oven temperature starting at 50 °C, finally
raised to 150 °C) to yield a colorless oil (980 mg, 5.69 mmol,
89%): Rf (SiO2, PE/MTB 1:1) ) 0.35; 1H NMR (CDCl3, 200 MHz)
δ 1.27 (t, J ) 7.1 Hz, 3 H), 2.04-2.17 (m, 3 H), 2.40-2.52 (m, 3
H), 3.67 (s, 1 H), 4.24 (q, J ) 7.1 Hz, 2 H) ppm; 13C{1H} NMR
(CDCl3, 50 MHz) δ 13.98 (CH3), 18.33 (CH2), 34.70 (CH2), 35.78
(CH2), 62.49 (CH2), 79.70 (C), 171.54 (CdO), 213.34 (CdO) ppm;
IR (ATR) 1/λ 3473 (s), 1756 (vs), 1729 (vs) cm-1; mol. mass calcd
172.0736, found 172.0734 (HRMS). Anal. Calcd for C8H12O4
(172.18): C, 55.81; H, 7.02. Found: C, 55.25; H, 7.11.
2-Oxoh ep ta n ed ioic a cid 1-eth yl ester (4): Rf (SiO2, PE/
1
MTB 1:1) ) 0.05, Rf (SiO2, MTB) ) 0.35; H NMR (CDCl3, 200
MHz) δ 1.32 (t, J ) 7.2 Hz, 3 H), 1.61-1.68 (m, 4 H), 2.32-2.38
(m, 2 H), 2.80-2.87 (m, 2 H), 4.27 (q, J ) 7.2 Hz, 2 H), 10.3 (s,
br., 1 H) ppm; 13C{1H} NMR (CDCl3, 50 MHz) δ 13.86 (CH3),
22.15 (CH2), 23.71 (CH2), 33.52 (CH2), 38.67 (CH2), 62.37 (CH2),
160.93 (CdO), 179.35 (CdO), 193.99 (CdO) ppm; IR (ATR) 1/λ
3500-2500 (s, br), 1727 (vs), 1710 (vs), 1406 (m), 1279 (s) cm-1
;
mol. mass calcd 202.0841, found 202.0842 (HRMS). Anal. Calcd
C9H14O5 (202.21): C, 53.46; H, 6.98. Found: C, 53.88; H, 6.94.
Eth yl cis-2,3-Ep oxy-3-h yd r oxy-3-p h en ylp r op a n oa te (5).
Following the procedure reported for 2b, oxoester 1d (1.00 g,
5.20 mmol) and Mn(OAc)2‚4H2O (64 mg, 0.26 mmol) were stirred
for 12 h at room temperature to yield after chromatography
(SiO2, PE/MTB 1:1, Rf ) 0.38) compound 5 (66 mg, 0.32 mmol,
6%) as a colorless oil. As a first fraction, starting material 1d
was recovered (ca. 80%): 1H NMR (CDCl3, 200 MHz) δ 1.29 (t,
J ) 7.1 Hz, 3 H; CH3), 1.65 (s, br, 1 H; OH), 4.17 (q, J ) 7.1 Hz,
2 H; CH2), 4.96 (s, 1 H; 2-H), 7.39-7.42 (m, 3 H; p- and m-H),
7.51-7.56 (m, 2 H; o-H) ppm; 13C{1H} NMR (CDCl3, 50 MHz) δ
14.54 (CH3), 58.87 (CH2), 84.59 (CH), 126.11 (CH), 128.77 (CH),
130.17 (CH), 137.64 (C), 160.44 (C), 170.38 (C) ppm; IR (ATR)
1/λ 3439 (m), 3327 (m), 1662 (s), 1615 (vs), 1576 (m), 1554 (vs),
1313 (s), 1174 (vs) cm-1; MS (EI, 70 eV) m/z 191 (66), 146 (100),
119 (92), 104 (42).
Eth yl 2-Hyd r oxycycloh exa n on e-2-ca r boxyla te (2b). Fol-
lowing the procedure reported for 2a , oxoester 1b (1.00 g, 5.87
mmol) was converted with a suspension of Mn(OAc)2‚4H2O (72
mg, 0.29 mmol) in CH2Cl2 (1 mL). After being stirred at room
temperature, the reaction mixture was directly chromatographed
(SiO2, PE/MTB 1:1, Rf ) 0.39) to yield 2b (809 mg, 4.43 mmol,
74%) as a colorless oil: 1H NMR (CDCl3, 200 MHz) δ 1.27 (t, J
) 7.1 Hz, 3 H), 1.64-1.85 (m, 4 H), 1.95-2.07 (m, 1 H), 2.49-
2.70 (m, 3 H), 4.22 (q, J ) 7.1 Hz, 2 H), 4.31 (s, 1 H) ppm; 13C-
{1H} NMR (CDCl3, 50 MHz) δ 13.95 (CH3), 21.92 (CH2), 26.99
(CH2), 37.60 (CH2), 38.83 (CH2), 62.02 (CH2), 80.61 (C), 169.99
(CdO), 207.29 (CdO) ppm; IR (ATR) 1/λ 3457 (m), 1720 (vs)
cm-1; mol. mass calcd 186.0892, found 186.0893 (HRMS). Anal.
Calcd for C9H14O4 (186.21): C, 58.05; H, 7.58. Found: C, 58.11;
H, 7.57.
Meth yl 2-Hyd r oxycycloh ep ta n on e-2-ca r boxyla te (2c).
Following the procedure reported for 2b, oxoester 1c (1.00 g,
5.88 mmol) was converted with Mn(OAc)2‚4H2O (71 mg, 0.29
mmol) to yield after chromatography (SiO2, PE/MTB 1:1, Rf )
0.35) 2c (896 mg, 4.82 mmol, 82%) as a colorless oil: 1H NMR
(CDCl3, 200 MHz) δ 1.21-1.47 (m, 3 H), 1.68-2.10 (m, 4 H),
2.21 (ddt, J ) 14.9 Hz, J ) 10.1 Hz, J ) 1.3 Hz, 1 H), 2.52 (ddd,
J ) 12.0 Hz, J ) 7.2 Hz, J ) 1.4 Hz, 1 H), 2.90 (td, J ) 12.0 Hz,
J ) 2.9 Hz, 1 H), 3.69 (s, 3 H), 4.29 (d, J ) 1.3 Hz, 1 H) ppm;
13C{1H} NMR (CDCl3, 50 MHz) δ 23.45 (CH2), 27.01 (CH2), 29.96
(CH2), 34.36 (CH2), 39.74 (CH2), 52.84 (CH3), 83.34 (C), 170.92
(CdO), 209.31 (CdO) ppm; IR (ATR) 1/λ 3474 (s), 1751 (vs), 1714
Ack n ow led gm en t. Support from the Deutsche For-
schungsgemeinschaft, the Fonds der Chemischen In-
dustrie, as well as from Prof. S. Blechert is gratefully
acknowledged.
Su p p or tin g In for m a tion Ava ila ble: NMR spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O9909094