Titanium(IV) chloride-mediated ortho-acylation of phenols and naphthols

Article abstract of DOI:10.1055/s-2003-36822

The use of titanium(IV) chloride as a Lewis acid for direct ortho-acylation of phenols and naphthols proves to be a convenient, more general and direct route to various hydroxyaryl ketones. The route is regioselective, leading to ortho C-acylated products in satisfactory to high yields in most cases.

Full text of DOI:10.1055/s-2003-36822

PAPER
267
Titanium(IV) Chloride-Mediated Ortho-Acylation of Phenols and Naphthols
O
rtho-Acylation o
h
f
Phenols lem Bensari, Nurulain T. Zaveri*
Biopharmaceutical Division, SRI International, Menlo Park, CA 94025, USA
Fax +1(650)8593153; E-mail: nurulain.zaveri@sri.com
Received 17 September 2002; revised 8 November 2002
product in good yield in some cases, no C-acylated prod-
Abstract: The use of titanium(IV) chloride as a Lewis acid for di-
rect ortho-acylation of phenols and naphthols proves to be a conve-
nient, more general and direct route to various hydroxyaryl ketones.
The route is regioselective, leading to ortho C-acylated products in
satisfactory to high yields in most cases.
uct was obtained with several of our substrates (e.g.,
Table 1, entries 4, 6, 13). These substrates mainly afford-
ed the O-acylated products (Table 1, footnotes). We re-
quired a more generally applicable method for direct
ortho C-acylation of different aryl alcohols.
Key words: ortho-acylation, Lewis acid, electrophilic substitution,
hydroxyaryl ketone, regioselectivity
The use of titanium(IV) compounds in selective C–C
bond forming reactions has been extensively explored for
decades, especially for Grignard, aldol, and Michael addi-
tions, and for substitution reactions.8 We wish to report
here the convenience and the effectiveness of using TiCl4
as a mediator for the direct ortho-acylation of phenols and
naphthols. The acylations were performed at 120 °C with-
out solvent using an equimolar amount of TiCl4 to the sub-
strate, to afford the corresponding ortho-acylated aryl
alcohol in good yields in most cases. Although the TiCl4-
mediated direct acylation of paracyclophanes has been re-
cently reported by Rozenberg et al.,3c their reaction condi-
tions (1.3 equiv TiCl4, RCOCl, CH2Cl2, r.t.) proved to be
specific only for paracyclophane and when used with an
alkyl-substituted phenol, mainly afforded the O-acylated
product along with small amounts of ortho and para C-
acylated products.
Hydroxyaryl ketones have significant applications in per-
fumery, metallurgy, and pharmaceutical industries. More-
over, compounds of this class are also important synthetic
intermediates in organic synthesis and versatile interme-
diates in the synthesis of biologically active compounds
such as chalcones, flavanones, naphthoquinones, and pes-
ticides. Although some hydroxyaryl ketones exist in na-
ture, non-natural hydroxyaryl ketones have been
synthesized by several methods from phenols and naph-
thols. Among these, Fries rearrangement of phenyl or
naphthyl esters in the presence of Lewis acids is one of the
common routes to these compounds.1 This reaction re-
quires more than a stoichiometric amount of strong Lewis
acid such as aluminum(III) chloride,2 although milder ac-
ids such as titanium(IV)3 or zirconium(IV)4 chloride have
also been used. The direct acylation of phenols and naph-
As seen from Table 1, our reported conditions are gener-
ally applicable to phenols and naphthols bearing a wide
range of substituents and with different electronic as well
as steric environments. The reaction is chemoselective in
that C-acylation is obtained in most cases, except with en-
tries 4 and 5, where very small amounts of O-acylated
product were also isolated (Table 1, footnotes). In all sub-
strates, particularly those with available para positions,
we only obtained the ortho C-acylated product and the
acylation occurred at the sterically least encumbered
neighboring carbon (entries 1–3, 12). No para-acylated
product was obtained in any case where the para position
was unsubstituted (entries 1–3, 6, 7, 9–11). In cases where
the yields were low (entry 25), 37% starting material was
recovered. The reaction is therefore as ortho-regioselec-
tive as the Fries rearrangement, but it proceeds smoothly
and in a very simple manner without any severe side reac-
tions, as are usually seen when AlCl3 is used under similar
conditions. No migration or loss of alkyl groups (entry 4)
or halogen (entry 14) was observed. Larger acid chlorides
can also be used as electrophiles for the acylation (entries
9, 10).
5
thols using stoichiometric AlCl3 has been reported but is
generally not regioselective and the drastic conditions re-
quired for the AlCl3-mediated direct acylation can cause
side reactions and dealkylation.1a To obtain ortho-regio-
selectivity, metal phenolates6 have also been employed to
assist in directing the acylation to the ortho position. More
recently, Kobayashi and co-workers have shown the ef-
fectiveness of group 3 and 4 metal triflates, Sc(OTf)3 and
Hf(OTf)4, in catalyzing not only the Fries rearrangement
of phenyl and naphthyl esters but also the direct ortho-
acylation of the free aryl alcohols.7 Therefore, much inter-
est is still being directed toward the search for new and
convenient approaches to this class of compounds as well
as the improvement of their classical synthesis.
During the course of our work, we required ortho-hy-
droxyaryl ketones with varied substitutions on the aryl
ring. We initially employed the catalytic Sc(OTf)3-medi-
ated direct ortho-acylation method [cat. Sc(OTf)3, tolu-
ene–nitromethane, 6 h, 100 °C)] reported by Kobayashi
and co-workers.7 While this method afforded the required
To account for the ortho-regioselective acylation of phe-
nols and naphthols, and as has been previously proposed
to explain similar ortho-directed electrophilic substitu-
tions involving metal phenolates,7 we assume that the re-
Synthesis 2003, No. 2, Print: 31 01 03.
Art Id.1437-210X,E;2003,0,02,0267,0271,ftx,en;M03902SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

268
A. Bensari, N. T. Zaveri
PAPER
action occurs by formation of an intermediate of mixed π- considered superior to the Fries rearrangement, since the
Ti(IV) phenolate complex with the acid chloride. The C-acylated adducts are obtained in one pot directly from
metal center thus simultaneously coordinates both reac- free phenols and naphthols. Other advantages of the meth-
tion partners, the acid chloride and the aryl alcohol. Such odology reported here are the short reaction time, general
coordination subsequently directs the electrophilic attack applicability to a wide range of substrates, and lack of
to the proximate ortho position of the aromatic ring.
competing side reactions. This methodology therefore
represents an important addition to the existing methodol-
ogies for the synthesis of hydroxyaryl ketones.
In summary, TiCl4 has proven effective in promoting the
direct ortho-acylation of phenols and naphthols at 120 °C
without solvent, leading to 2-hydroxyphenyl ketones and
2-hydroxynaphthyl ketones. The present procedure can be
Table 1 TiCl4-Mediated Ortho-Acylation of Phenols and Naphthols
Entry
1
ArOH
R′
Product
Yield (%)a,b
95
OH
OH
O
R = Me
CH3
2a
2b
2c
CH3
2
3
R = OMe CH3
82
51
R
R
R = t-Bu
CH3
CH3
74c,d
OH
O
4
2d
OH
CH3
5
6
CH3
CH3
2e
2f
68e
84f
OH
Me
OH
Me
O
CH3
OH
OH
O
CH3
Me
Me
Me
OH
Me
OH
7
8
CH3
CH3
CH3
C2H5
2g
2h
2i
25g
57
76
85
O
CH3
CH3
OH
OH
O
9
OH
OH
O
O
OH
OH
R'
R'
10
2j
OH
11
OH
O
2k
60
R'
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Ortho-Acylation of Phenols and Naphthols
269
Table 1 TiCl4-Mediated Ortho-Acylation of Phenols and Naphthols (continued)
Entry
12
ArOH
R′
Product
Yield (%)a,b
59
CH3
2l
OH
OH
CH3
O
13
14
15
OH
CH3
CH3
CH3
2m
82
63
90
OH
O
CH3
OMe
OH
OMe
2n
2o
OH
O
CH3
Cl
Cl
OH
OH
O
CH3
Me
Me
a Isolated yields.
b No para-substituted product was isolated in any case.
c 12% of the O-acyl ester was also isolated.
d The similar reaction using catalytic Sc(OTf)3 as Lewis acid gave only 8% of the desired C-acylated product and 8% of the O-acylated product.
e Less than 2% of the O-acylated product obtained.
f The similar reaction using catalytic Sc(OTf)3 as Lewis acid according to the method of Kobayashi et al.,5 gave no C-acylated product and only
8% of the O-acylated product was isolated.
g 37% of the starting material was also recovered.
1-(2-Hydroxy-4-methylphenyl)ethanone (2a)
Melting points are uncorrected. NMR (1H 300 MHz, 13C 75 MHz)
spectra were recorded on a Varian L900 Gemini 300 instrument us-
ing CDCl3 with tetramethylsilane as the internal standard. IR spec-
tra were recorded on Perkin Elmer 1600 IR spectrophotometer.
Mass spectra were obtained on a Finnigan LCQTM DUO mass spec-
trometer using either electrospray ionization in positive or negative
mode (ESI) or the atmospheric pressure chemical ionization (APCI)
mode. Elemental analyses were performed by Atlantic Microlabs,
Norcross, GA and are given only for previously uncharacterized
compounds.
Oil (Lit.9 bp 82–84 °C/0.6 Torr).
IR (neat): 3003, 1636 cm–1.
1H NMR (CDCl3): δ = 2.35 (s, 3 H), 2.59 (s, 3 H), 6.70 (dd, 1 H,
J = 1.20, 8.40 Hz), 6.78 (d, 1 H, J = 1.20 Hz), 7.61 (d, 1 H, J = 8.40
Hz), 12.28 (s, 1 H).
13C NMR (CDCl3): δ = 22.16, 26.68, 117.81, 118.64, 120.41,
130.81, 148.29, 162.74, 204.08.
MS (ESI): m/z = 151 (M + 1).
1-(2-Hydroxy-4-methoxyphenyl)ethanone (2b)
Mp 70–72 °C.
IR (KBr): 2930, 1628, 1256 cm–1.
1H NMR (CDCl3): δ = 2.55 (s, 3 H), 3.84 (s, 3 H), 6.42 (s, 1 H), 6.44
(d, 1 H, J = 8.40 Hz), 7.63 (d, 1 H, J = 8.40 Hz), 12.74 (s, 1 H).
TiCl4-Mediated Direct Ortho-Acylation; Typical Procedure
TiCl4 (1.2 mL, 11 mmol) was slowly added to 10 mmol of starting
phenol or naphthol placed in a flask flushed with argon at r.t. The
resulting dark cherry-colored mixture was stirred at r.t., and when
gas evolution had ceased, the appropriate acid chloride (15 mmol)
was added to the solid. The resulting thick solution was stirred at r.t.
for 15 min, then brought to 120 °C and left to stir at this temperature
for an additional hour. The reaction mixture was then cooled to r.t.,
diluted with CH2Cl2 (30 mL) and quenched with H2O (30 mL). Only
for entries 7 and 8 (Table 1), a slurry of TiO2 was observed upon
workup. In this case, the mixture was diluted with aq 2 N HCl (30
mL) and the biphasic mixture was filtered through a pad of Celite.
In all other cases, a cloudy solution was obtained which was easily
extracted with CH2Cl2. The organic layer was washed with H2O (2
× 30 mL), dried (Na2SO4), and concentrated under reduced pres-
sure. The crude material was purified by silica gel column chroma-
tography using a mixture of hexanes–EtOAc.
13C NMR (CDCl3): δ = 26.41, 55.78, 101.07, 107.84,114.14,
132.50, 165.50, 166.35, 202.77.
MS (ESI): m/z = 167 (M + 1).
Anal. Calcd for C9H10O3: C, 77.38; H, 9.74. Found: C, 77.44; H,
9.77.
1-(4-tert-Butyl-2-hydroxyphenyl)ethanone (2c)
Oil.
IR (neat): 2965, 1643 cm–1.
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A. Bensari, N. T. Zaveri
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1H NMR (CDCl3): δ = 1.31 (s, 9 H), 2.60 (s, 3 H), 6.94 (dd, 1 H,
J = 1.8, 8.10 Hz), 6.99 (d, 1 H, J = 1.8 Hz), 7.66 (d, 1 H, J = 8.40
Hz).
13C NMR (CDCl3): δ = 26.70, 31.00, 35.54, 115.28,16.85, 117.67,
130.60, 161.29, 162.58, 204.00.
13C NMR (CDCl3): δ = 26.86, 41.15, 118.77, 119.74, 126.57,
128.86, 128.97, 130.72, 131.71, 137.58, 140.94, 161.10, 204.65.
MS (ESI): m/z = 227 (M + 1).
Anal. Calcd for C15H14O2: C, 79.62; H, 6.24. Found: C, 79.78; H,
6.25.
MS (ESI): m/z = 193 (M + 1).
1-(1-Hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)ethanone (2i)
1-(3,5-Di-tert-butyl-2-hydroxyphenyl)ethanone (2d)
Mp 52–54 °C.
Oil.
IR (KBr): 2936, 1623, 1428 cm–1.
IR (neat): 2959, 1634 cm–1.
1H NMR (CDCl3): δ = 1.32 (s, 9 H), 1.43 (s, 9 H), 2.65 (s, 3 H), 7.56
1H NMR (CDCl3): δ = 1.78 (m, 4 H), 2.59 (s, 3 H), 2.68 (t, 2 H,
J = 5.4 Hz), 2.76 (t, 2 H, J = 5.4 Hz), 6.61 (d, 1 H, J = 8.1 Hz), 12.72
(s, 1 H).
(m, 2 H), 12.98 (s, 1 H).
13C NMR (CDCl3): δ = 27.09, 29.34, 31.36, 34.24, 35.12, 118.75,
13C NMR (CDCl3): δ = 22.56, 22.59, 22.61, 26.68, 30.54, 116.85,
124.34, 131.36, 138.02, 140.07, 160.07, 205.21.
119.82, 126.66, 127.23, 147.04, 161.11, 204.34.
MS (ESI): m/z = 249 (M + 1).
MS (ESI): m/z = 191 (M + 1).
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.72; H,
7.50.
1-[3-(1-Adamantyl)-2-hydroxy-5-methylphenyl]ethanone (2e)
Mp 148–150 °C.
IR (KBr): 2921, 1627, 1440 cm–1.
1-(1-Hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)propan-1-one
(2j)
Mp 86–88 °C.
IR (KBr): 2933, 1630, 1406 cm–1.
1H NMR (CDCl3): δ = 1.78 (m, 6 H), 2.08 (m, 3 H), 2.14 (m, 6 H),
2.30 (s, 3 H), 2.62 (s, 3 H), 7.23 (d, 1 H, J = 2.1 Hz), 7.39 (d, 1 H,
J = 2.1 Hz), 13.0 (s, 1 H).
13C NMR (CDCl3): δ = 21.13, 27.33, 29.24, 37.30, 40.42, 119.36,
127.03, 128.33, 135.12, 138.86, 160.63, 205.40.
1H NMR (CDCl3): δ = 1.26 (t, 3 H, J = 7.3 Hz), 1.75-1.81 (m, 4H),
2.69 (t, 2H, J = 6.3 Hz), 2.75 (t, 2H, J = 6.3 Hz), 3.0 (q, 2H, J = 7.3
Hz).
13C NMR (CDCl3): δ = 8.76, 22.59, 22.63, 30.51, 31.59, 116.28,
119.74, 126.38, 126.74, 146.66, 161.11, 207.07.
MS (APCI): m/z = 285 (M + 1).
Anal. Calcd for C19H24O2: C, 80.24; H, 8.51. Found: C, 80.26; H,
8.61.
MS (APCI): m/z = 205 (M + 1), 187.
1-(2-Hydroxy-4,6-dimethylphenyl)ethanone (2f)
Mp 58–60 °C.
IR (KBr): 2927, 1622, 1353, 1216 cm–1.
Anal. Calcd for C13H16O2: C, 76.44; H, 7.90. Found: C, 76.51; H,
7.96.
Cyclohexyl(1-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-
methanone (2k)
Mp 110–112 °C.
IR (KBr): 2928, 1617, 1408 cm–1.
1H NMR (CDCl3): δ = 1.23–1.89 (m, 14 H), 2.68 (t, 2 H, J = 6 Hz),
2.75 (t, 2 H, J = 6 Hz), 3.27 (tt, 1 H, J = 3, 11.2 Hz), 6.60 (d, 1 H,
J = 8.2 Hz), 13.07 (s, 1 H).
13C NMR (CDCl3): δ = 22.61, 22.64, 22.69, 26.06, 26.11, 29.89,
30.51, 45.26, 115.32, 119.61, 126.34, 126.97, 146.67, 161.90,
209.98.
1H NMR (CDCl3): δ = 2.27 (s, 3 H), 2.56 (s, 3 H), 2.63 (s, 3 H), 6.54
(s, 1 H), 6.65 (s, 1 H), 12.64 (s, 1 H).
13C NMR (CDCl3): δ = 21.77, 24.87, 33.47, 116.94, 119.31, 124.70,
139.65, 146.32, 163.79, 205.64.
MS (ESI): m/z = 165 (M + 1).
Anal. Calcd for C10H12O2: C, 73.15; H, 7.37. Found: C, 73.33; H,
7.37.
1-(3-Benzyl-2-hydroxyphenyl)ethanone (2g)
Oil.
MS (ESI): m/z = 259 (M + 1).
IR (neat): 3026, 1634 cm–1.
Anal. Calcd for C17H22O2: C, 79.03; H, 8.58. Found: C, 78.88; H,
8.59.
1H NMR (CDCl3): δ = 2.62 (s, 3 H), 4.01 (s, 2 H), 6.81 (t, 1 H,
J = 7.5 Hz), 7.24–7.28 (m, 6 H), 7.61 (dd, 1 H, J = 1.50, 7.5 Hz),
12.64 (s, 1 H).
13C NMR (CDCl3): δ = 26.99, 35.35, 118.64, 119.57, 126.31,
128.64, 129.11, 129.21, 130.82, 137.13, 140.43, 160.71, 204.95.
1-(3-Hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)ethanone (2l)
Mp 70–72 °C.
IR (KBr): 2934, 1621, 1491, 1344 cm–1.
1H NMR (CDCl3): δ = 1.77 (m, 4 H), 2.59 (s, 3 H), 2.76 (m, 4 H),
6.68 (s, 1 H), 7.41 (s, 1 H), 11.96 (s, 1 H).
13C NMR (CDCl3): δ = 22.87, 23.42, 26,72, 28.82, 30.17, 117.82,
MS (ESI): m/z = 227 (M + 1).
Anal. Calcd for C15H14O2: C, 79.62; H, 6.24. Found: C, 79.76; H,
6.28.
118.21, 128.10, 131.04, 147.71, 160.09, 204.16.
1-(5-Benzyl-2-hydroxyphenyl)ethanone (2h)
Oil.
MS (ESI): m/z = 191 (M + 1).
IR (neat): 3027, 1642 cm–1.
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.91; H,
7.46.
1H NMR (CDCl3): δ = 2.58 (s, 3 H), 3.95 (s, 2 H), 6.92 (d, 1 H,
J = 8.7 Hz), 7.15–7.31 (m, 6 H), 7.52 (d, 1 H, J = 2.1 Hz), 12.14 (s,
1 H).
Synthesis 2003, No. 2, 267–271 ISSN 0039-7881 © Thieme Stuttgart · New York

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Ortho-Acylation of Phenols and Naphthols
271
1-(1-Hydroxy-4-methoxy-2-naphthyl)ethanone (2m)
Number 6JB-0068, N. Z.) and the California Cancer Research Pro-
gram of the California Department of Health Services (Grant Num-
ber 2PF 0168, N. Z.)
Mp 118–120 °C (Lit.7d mp 120–122 °C).
IR (KBr): 2907, 1628, 1453, 1393 cm–1.
1H NMR (CDCl3): δ = 2.69 (s, 3 H), 3.99 (s, 1 H), 6.84 (s, 1 H),
7.54–7.60 (m, 1 H), 7.63–7.69 (m, 1 H), 8.18 (d, 1 H, J = 8.2 Hz),
13.75 (s, 1 H).
13C NMR (CDCl3): δ = 27.25, 55.96, 101.13, 112.22, 122.13,
124.63, 126.20, 126.86, 129.98, 130.55, 147.66, 157.70, 203.90.
References
(1) For reviews on the Fries rearrangement, see (a) Martin, R.
Org. Prep. Proced. Int. 1992, 24, 369. (b) See also: Shine,
H. J. In Aromatic Rearrangements; Elsevier: New York,
1967, 72. (c) See also: Gerecs, A. The Fries rearrangement,
In Friedel–Crafts and Related Reactions, Vol. III; Olah, G.
A., Ed.; Interscience: New York, 1964, Part 1, 499.
(2) (a) Fries, K.; Finck, G. Ber. Dtsch. Chem. Ges. 1908, 41,
4271. (b) Fries, K.; Pfaffendorf, W. Ber. Dtsch. Chem. Ges.
1910, 43, 212.
(3) (a) Martin, R.; Demerseman, P. Synthesis 1989, 25.
(b) Martin, R.; Demerseman, P. Synthesis 1992, 738.
(c) Rozenberg, V.; Danilova, T.; Sergeeva, E.; Vorontzov,
E.; Starikova, Z.; Lysenko, K.; Belokon, Y. Eur. J. Org.
Chem. 2000, 3295.
MS (ESI): m/z = 217 (M + 1).
1-(4-Chloro-1-hydroxy-2-naphthyl)ethanone (2n)
Mp 122–124 °C.
IR (KBr): 3030, 1623, 1382, 1230 cm–1.
1H NMR (CDCl3): δ = 2.69 (s, 3 H), 7.61 (ddd, 1 H, J = 1.2, 6.9, 8.2
Hz), 7.74 (s, 1 H), 7.76 (ddd, 1 H, J = 1.2, 6.9, 8.2 Hz), 8.18 (d, 1 H,
J = 8.2 Hz), 8.51 (s, 1 H, J = 8.2 Hz).
13C NMR (CDCl3): δ = 26.85, 113.14, 121.28, 124.37, 124.40,
124.87, 126.33, 126.75, 131.05, 134.32, 161.45, 203.42.
(4) Harroweven, D. C.; Dainty, R. F. Tetrahedron Lett. 1996,
37, 7659.
MS (ESI): m/z = 219 (M – 1).
(5) (a) The original work: Niyazov, A. N.; Namatov, B.; Atlyev,
K. Izv. Akad. Nauk Turkm. SSR. Ser. Fiz.-Tekh., Khim. Geol.
Nauk. 1974, 62; Chem. Abstr. 1975, 82, 170275. (b) Trost,
B. M.; Saulnier, M. G. Tetrahedron Lett. 1985, 26, 123.
(c) Crombie, L.; Jones, R. C. F.; Palmer, C. J. Tetrahedron
Lett. 1985, 26, 2933.
Anal. Calcd for C12H9ClO2: C, 65.32; H, 4.11. Found: C, 65.10; H,
4.15.
1-(4-Hydroxy-7-methyl-2,3-dihydro-1H-inden-5-yl)ethanone
(2o)
Mp 70–72 °C.
(6) Sartori, G.; Gasnati, G.; Bigi, F. J. Org. Chem. 1990, 55,
4371; and references cited therein.
IR (KBr): 2910, 1627, 1451 cm–1.
1H NMR (CDCl3): δ = 2.12 (q, 2 H, J = 7.5 Hz), 2.21 (s, 3 H), 2.59
(s, 3 H), 2.85 (t, 2 H, J = 7.5 Hz), 2.92 (t, 2 H, J = 7.5 Hz), 7.33 (s,
1 H), 12.25 (s, 1 H).
13C NMR (CDCl3): δ = 18.67, 24.53, 26.99, 29.20, 32.91, 118.39,
124.36, 129.57, 131.84, 153.96, 157.28, 204.39.
(7) (a) Kobayashi, S.; Moriwaki, M.; Hachiya, I. J. Chem. Soc.,
Chem. Commun. 1995, 1527. (b) Kobayashi, S.; Moriwaki,
M.; Hachiya, I. Synlett 1995, 1153. (c) Kobayashi, S.;
Moriwaki, M.; Hachiya, I. Tetrahedron Lett. 1996, 37,
2053. (d) Kobayashi, S.; Moriwaki, M.; Hachiya, I. Bull.
Chem. Soc. Jpn. 1997, 70, 267.
(8) (a) For overviews, see: Reetz, M. T. Organotitanium
Reagents in Organic Synthesis; Springer-Verlag: New York,
1986. (b) Reetz, M. T. Organotitanium Chemistry, In
Organometallics in Synthesis, 2nd ed.; Schlosser, M., Ed.;
Wiley: New York, 2002.
MS (APCI): m/z = 191 (M + 1).
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.77; H,
7.43.
Acknowledgments
(9) Julia, M.; Chastrette, F. Bull. Chem. Soc. Fr. 1962, 2255.
This work was supported by funds from the California Breast
Cancer Research Program of the University of California (Grant
Synthesis 2003, No. 2, 267–271 ISSN 0039-7881 © Thieme Stuttgart · New York