Transition metal-catalyzed oxidations. 12 : α-Chlorination of silylenol ethers with tert-butyl hydroperoxide and TiCl2(OiPr)2

Article abstract of DOI:10.1002/(SICI)1521-3897(199901)341:1<62::AID-PRAC62>3.0.CO;2-B

Enolsilyl ethers (4, 6, 8, 10, 12, 14) are chlorinated to the α-monochloro ketones (5, 7, 9, 11, 13, 15) with tert-butyl hydroperoxide in the presence of dichlorotitanium diisopropoxide in 69 - 92% yield. WILEY-VCH Verlag GmbH, 1999.

Full text of DOI:10.1002/(SICI)1521-3897(199901)341:1<62::AID-PRAC62>3.0.CO;2-B

_____________________________________________________________________PROCEDURES/DATA
Transition Metal-Catalyzed Oxidations. 12 [1]
α-Chlorination of Silylenol Ethers with tert-Butyl Hydroperoxide and TiCl2(OiPr)2
Karsten Krohn*, Klaus Steingröver, and Ingeborg Vinke
Paderborn, Universität-GH, FB 13- Fachbereich Chemie und Chemietechnik
Received October 20th, 1998
Keywords: Chlorine, Ketones, Oxidations, Titanium, Silylenol ethers
Dedicated to Prof. H. Marsmann on the Occasion of his 60th Anniversary
Abstract. Enolsilyl ethers (4, 6, 8, 10, 12, 14) are chlorinat-
ed to the α-monochloro ketones (5, 7, 9, 11, 13, 15) with
tert-butyl hydroperoxide in the presence of dichlorotitanium
diisopropoxide in 69 – 92% yield.
In preceding communications we described the oxygenation
of the vinylic position of phenols such as naphthol (1) to form
selectively the ortho-quinones 2 (R = H, Scheme 1) [2, 3] or
the transformation to unsaturated α-hydroxy ketones 3
(R = methyl) [4]. tert-Butyl hydroperoxide (TBHP) was used
as the oxidant and transition metal alkoxides served as the
catalysts. These results suggested to try the α-hydroxylation
of enolates with this system to test if the methods of Vedejs
[5] using the Mimoun molybdenumoxodiperoxo complex or
that of Davies [6] employing N-sulfonyloxaziridines could
be improved using less expensive and environmentally safe
reagents.
10, 12, and 14 obtained in 93 – 98% yield in the usual manner
by deprotonation of the corresponding ketones with LDA and
quenching with trimethylsilyl chloride. The reaction with the
dichlorotitanium complex TiCl2(OiPr)2 proved to be superior
as compared with the monochloro compound TiCl(OiPr)3
employed in the chlorination of phenols [1]. Furthermore, the
addition of small amounts of pyridine with THF as the solvent
was advantageous to prevent premature acid-catalyzed
cleavage of the silylenol ethers.
OSiMe3
O
78 %
Cl
O
OH
O
cat/
4
cat/
TBHP
5
CH3
OH
R
TBHP
O
OSiMe3
O
CH3
74 %
CH3
Cl
R = H
R = CH3
3
1
2
6
8
7
9
OSiMe3
O
Scheme 1
69 %
Cl
Preliminary experiments with titanium or zirconium alk-
oxides and TBHP in the reaction of titanium enolates lead to
reprotonation of the enolates. The problem was recently
overcome by Schulz et al. [7] by using lithium tert-butyl
hydroperoxide as the oxidant. However, in connection with
the halogenation of phenols [1] we wondered if titanium
enolates could be converted to the α-chlorinated ketones by
the TiClm(OiPr)n/TBHP system. α-Chloroketones are required
in a number of transformations for instance in the Favorskii-
reaction [8, 9], the preparation of oxazoles [10] or thio-
carboxylic acids [11]. In fact, the anticipated chlorination
reaction turned out to be feasible, and we now report on the
convenient and effective α-chlorination of enolsilyl ethers
with TiCl2(OiPr)2/TBHP to yield α-chloroketones.
92 %
OSiMe3
O
10
11 Cl
OSiMe3
OSiMe3
O
69 %
83 %
Cl
12
14
13
15
O
Cl
Scheme 2
Three cyclic ketones of different steric hindrance and ring
size and three open chain ketones were selected to test the
chlorination reaction. The corresponding titanium enolates
were prepared via the corresponding silylenol ethers 4, 6, 8,
The isolated yields of 69 – 92% of the α-monochloro ketones
5, 7, 9, 11, 13, and 15 (Scheme 2) compare favorably with
62
© WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999 1436-9966/99/34101-62 $ 17.50 + .50/0
J. Prakt. Chem. 1999, 341, No. 1

α-Chlorination of Silylenol Ethers with tert-Butyl Hydroperoxide and TiCl (OiPr)
___________________________________________________________________________2 ___________ PROCEDURES/DATA
2
α-Chlorination of Silylenol Ethers with Cl2Ti(OiPr)2
(General Procedure)
known methods of chlorination of silylenol ethers [12–21].
Polychlorinations can usually not be excluded in the reaction
of ketones with elementary chlorine [15] or polyhalogenated
organic compounds [16, 17]. Most other methods require more
expensive (e.g. MCPBA [13]) or toxic reagents such as lead
salts [14], and the method presented here offers clear advan-
tages in terms of operational simplicity, yields, and environ-
mental safety. However, attempts for enantioselective
chlorination of the enolsilyl ethers with chirally modified
titanium catalysts were not yet successful (maximum ca. 30%
e.e.).
A solution of the silylenol ether (1 mmol) in dry THF (10 ml)
was treated with pyridine (0.32 ml, 4 mmol) and powdered
molecular sieve (3 Å, 50 mg). After 15 min of stirring
TiCl2(OiPr)2 (2.1 ml, 1.05 mmol, 0.5 mol/l in CH2Cl2,
prepared by reaction of equivalent amounts of TiCl4 and
Ti(OiPr)4) was added. The suspension was stirred for 45 min
at room temperature and TBHP (1.0 ml, 3 mmol, 3 mol/l in
CH2Cl2) was added at –50 °C. The cooling bath was removed
after 1 h, and stirring was continued for 12 h at room tem-
perature. The mixture was quenched by addition of water (10
ml), the suspension was filtered, and the phases were sepa-
rated. The aqueous phase was extracted with CH2Cl2 (15 ml),
the combined organic phases were washed with 10% HCl (5
ml), dried (MgSO4), the solvent was evaporated at reduced
pressure, and the residue purified by chromatography on silica
gel (CH2Cl2); yields see Scheme 2.
OR
OR
Ti
O
O
O
Cl−
A
2-Chloro-1-tetralone (5) [14]
Under mechanistic aspects, two pathways can be con-
sidered. On the one hand, the TiCl2(OiPr)2/TBHP system can
oxidize the chloride to an electrophilic chlorine species such
as hypochlorite that can attack the double bond of the enol
ether. On the other hand, a transition state such as A (Chart
1), similar to that assumed for the naphthol oxidation (Scheme
1), cannot be excluded [4]. It is known that titanium enolates
are generated from the enolsilyl ethers and titanium tetra-
chloride [22]. The titanium enolate can exchange one ligand
by attack of tert-butyl hydroperoxide and formation of
transition state A. The α-chloroketones are then formed by
attack of chloride.
1H NMR (200 MHz, CDCl3): δ/ppm = 2.41–2.71 (m 2H, 4-
H), 2.96–3.10 (m, 1H, 3-H), 3.26–3.41 (m, 1H, 3-H'), 4.67
(dd, J = 7.54 Hz, J = 4,03 Hz, 1H, 2-H), 7.29–7.42 (m, 2H, 5-
H, 7-H), 7.56 (m, 1H, 6-H), 8.12 (dd, J8,7 = 7.81 Hz, J8,6
=
1.18 Hz, 1H, 8-H). – 13C NMR (50 MHz , CDCl3): δ/ppm =
26.7 (t, C-4), 32.8 (t, C-3), 60.4 (d C-2), 127.5 (d, C-7)*, 129.0
(d, C-5)*, 129.1 (d, C-6), 130.9 (s, C-9), 134.6 (d, C-8), 143.7
(s, C-10), 191.3 (s, C-1).
2-Chloro-2-methyl-1-tetralone (7) [24]
1H NMR (200 MHz, CDCl3): δ/ppm = 1.86 (s, 3H, CH3),
2.3–2.5 (m, 2H, 4-H), 2.7–3.0 (m, 1H, 3-H), 3.3–3.4 (m,
1H, 3-H’), 7.2–7.6 (m, 3H, Ar-H), 8.1 (d, J8,7 = 6,6 Hz, 1H,
8-H). – 13C NMR (50 MHz , CDCl3): δ/ppm = 26.4 (q, CH3),
27.0 (t, C-4), 38.8 (t, C-3), 68.1 (s, C-2), 127.4 (d, C-7)*,
129.1 (d, C-5)*, 129.2 (d, C-6)*, 130.1 (s, C-9), 134.2 (d, C-
8), 143.5 (s, C-10), 191.7 (s, C-1).
We thank the Deutsche Forschungsgemeinschaft for financial
support of this work.
Experimental
2-Chloroindanone (9)
For general methods and instrumentation see [23]. The
assignment in signals marked with * is interchangeable.
1H NMR (200 MHz, CDCl3): δ/ppm = 3.34 (dd, J3,3' = 17.60
Hz, J3,2 = 3.92 Hz, 1H, 3-H), 4.16 (dd, J3',3 = 17.61 Hz, J3',2 =
7.74 Hz, 1H, 3-H'), 4.59 (dd, J2,3 = 7.75 Hz, J2,3' = 4.02 Hz,
1H, 2-H), 7.2–7.8 (m, 4H, Ar-H). – 13C NMR (50 MHz ,
CDCl3): δ/ppm = 37.9 (t, C-3), 56.3 (d, C-2), 125.4 (d, C-4)*,
126.9 (d, C-6)*, 128.8 (d, C-5)*, 129.9 (s, C-8), 136.5 (d, C-
7), 151.2 (s, C-9), 199.7(s, C-1).
Preparation of Silylenol Ethers 4, 6, 8, 10, 12, 14
The silylenol ethers 4, 6, 8, 10, 12, and 14 were prepared in
the usual manner by treatment of the corresponding ketones
(10 mmol) with LDA (13 mmol) in dry THF (–60 °C to
0 °C). The products were purified by bulb to bulb distillation
(yields 90 – 96%) and characterized by 1H NMR (200 MHz,
CDCl3). – 1H NMR data for 4: δ/ppm= 0.34 (s, 9H, Si(CH3)3),
2.40 (m, 2H, 3-H), 2.84 (t, J4,3 = 7.9 Hz, 2H, 3-H), 5.27 (t, J2,3
= 4.6 Hz, 1H, 2-H), 7.1–7.3(m, 3H, Ar-H), 7.49 (d, J8,7 = 6.5
Hz, 1H, 8-H). 6: δ/ppm = 0.34 (s, 9H, Si(CH3)3), 1.96 (s, 3H,
CH3), 2.37 (t, J3,4 = 7.91 Hz, 2H, 3-H), 2.87(t, J4,3 = 7.87 Hz,
2H, 4-H), 7.1–7.5(m, 4H, Ar-H). 8: δ/ppm = 0.37 (s, 9H,
2-Chloro-2-phenylacetophenone (Desylchlorid) (11)
1
m.p. 62 °C (Lit. [25]: 62–63 °C). – H NMR (200 MHz,
CDCl3): δ/ppm = 6.42 (s, 1H, 2-H), 7.3–8.1 (m, 10 H, Ar-H).
2-Chloroacetophenone (13)
m.p. 53 °C (Lit. [26] 53.5–54.2 °C). – 1H -NMR (200 MHz,
CDCl3): 4.76 (s, 2H, 2-H), 7.5–7.7 (m, 3H, 3'-H, 4'-H), 7.98
(dd, J2',3' = 7.05 Hz, J = 1.48 Hz, 2H, 2'-H). – 13C NMR
(50 MHz, CDCl3): 46.6 (t, C-2), 128.9 (d, C-3'), 129.3 (d, C-
4'), 134.5 (d, C-2'), 134.6 (s, C-1'), 191.5 (s, C-1).
Si(CH3)3), 3.35 (d, J3,2 = 2.34 Hz, 2H, 3-H), 5.52 (t, J2,3
=
2.34 Hz, 1H, 2-H), 7.3–7.5 (m, 4H, Ar-H). 10: δ/ppm = 0.14
(s, 9H, Si(CH3)3), 6.22 (s, 1H, 2-H), 7.1–7.8 (m, 10H, Ar-H).
12: δ/ppm = 0.34 (s, 9H, Si(CH3)3), 4.49 (d, J2,2' = 1.06 Hz,
1H, 2-H), 4.98 (d, J2',2 = 1.05 Hz, 1H, 2-H'), 7.3–7.7 (m, 5H,
2-Chloro-1-phenyl-1-propanone (15) [27]
1H NMR (200 MHz, CDCl3): δ/ppm = 1.77 (d, J3,2 = 6.67 Hz,
3H, 3-H), 5.29 (q, J2,3 = 6.66 Hz, 1H, 2-H), 7.5–7.7 (m, 3H,
3'-H, 4'-H), 8.04 (dd, J2',3' = 6.97 Hz, J = 1.61 Hz, 2H, 2′-H).
Ar-H). 14: δ/ppm = 0.24 (s, 9H, Si(CH3)3), 1.83 (d, J3,2
=
6.86 Hz, 3H, 3-H), 5.42 (q, J2,3 = 6.86 Hz, 1H, 2-H), 7.3–7.6
(m, 5H, Ar-H).
J. Prakt. Chem. 1999, 341, No. 1
63

K. Krohn, K. Steingröver, I. Vinke
PROCEDURES/DATA_______________________________________________________________________
–
13C NMR (50 MHz, CDCl3): δ/ppm = 20.4 (q, C-3), 53.2
Methoden Org. Chem. (Houben-Weyl), 4. ed., vol. 5/3, Ge-
org Thieme Verlag, Stuttgart 1962, p. 503
(d, C-2), 129.2 (d, C-3ς)*, 129.4 (d, C-4')*, 134.2 (d, C-2'),
134.5 (s, C-1'), 194.0 (s, C-1).
[16] A. Guy, M. Lemaire, J. P. Guette, Synthesis 1982, 1018
[17] P. D. Croce, R. Ferraccioli, A. Ritieni, Synthesis 1990, 212
[18] K.-J. Kim, K. Kim, Tetrahedron Lett. 1997, 38, 4227
[19] G. A. Hiegel, K. B. Peyton, Synth. Commun. 1985, 15, 385
[20] T. Tsuruta, T. Harada, H. Nishino, K. Kurosawa, Bull. Chem.
Soc. Jpn. 1985, 58, 142
[21] N. De Kimpe, W. De Cock, N. Schamp, Synthesis 1987, 188
[22] E. Nakamura, J. Shimada, Y. Horiguchi, I. Kuwajima, Tetra-
hedron Lett. 1983, 24, 3341
References
[1] Part 11: K. Krohn, H. Rieger, Steingröver K., I. Vinke, J.
prakt. Chem. 1998, 59, 341
[2] K. Krohn, H. Rieger, K. Khanbabaee, Chem. Ber. 1989, 122,
2323
[3] K. Krohn, H. Rieger, K. Brüggmann, Synthesis 1990, 1141
[4] K. Krohn, K. Brüggmann, D. Döring, P. G. Jones, Chem.
Ber. 1992, 125, 2439
[5] E. Vedejs, J. Am. Chem. Soc. 1974, 96, 5944
[6] F. A. Davis, B.-C. Chen, Chem. Rev. 1992, 92, 919
[7] M. Schulz, R. Kluge, M. Schüßler, G. Hoffmann, Tetrahe-
dron 1995, 51, 3175
[8] A. Favorskii, J. prakt. Chem. 1895, 51, 533
[9] H. H. Wassermann, G. M. Clark, P. C. Turley, Top. Curr.
Chem. 1974, 47, 73
[23] K. Krohn, A. Michel, U. Flörke, H.-J. Aust, S. Draeger, B.
Schulz, Liebigs Ann. Chem. 1994, 1093
[24] F. A. Davis, M. C. Weismiller, C. K. Murphy, R. R. Reddy,
B.-C. Chen, J. Org. Chem, 1992, 57, 7274
[25] W. Bergmark, C. De Wang, D. Whitten, J. Am. Chem. Soc.
1992, 114, 8810
[26] G. A. Hiegel, K. B. Peyton, Synth. Commun. 1985, 15, 385
[27] A. Kohda, K. Ueda, T. Sato, J. Org. Chem. 1981, 46, 509
[10] B. S. Friedmann, M. Sparks, R. Adams, J. Am. Chem. Soc.
1937, 59, 2262
[11] F. Asinger, M. Thiel, Angew. Chem. 1958, 70, 667
[12] G. A. Olah, L. Ohannesian, M. Arvanaghi, G. K. S. Prakash,
J. Org. Chem. 1984, 49, 2032
Address for correspondence:
Prof. K. Krohn
Fachbereich Chemie und Chemietechnik
der Univ.-GH Paderborn
[13] H. J. Kim, H. R. Kim, E. K. Ryu, Synthetic Comm. 1990,
Warburger Str. 100
20,1625
D-33098 Paderborn
[14] S. Motohashi, M. Satomi, Synthesis 1982, 1021
[15] R. Stroh, W. Hahn, Herstellung von Chlorverbindungen. in
FAX: internat. code (0) 5251-60-3245
E-mail: kk@chemie.uni-paderborn.de
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J. Prakt. Chem. 1999, 341, No. 1