Nucleophilic reactions of propargyl acetates mediated by titanocene dichloride and magnesium

Article abstract of DOI:10.1016/S0040-4039(01)00309-4

Reaction of Cp₂TiCl₂/Mg with propargyl acetates form allenyl titanium intermediates, which undergo nucleophilic addition reactions to aldehydes or ketones to give homopropargyl alcohols in high yields. Subsequent nucleophilic additio

Full text of DOI:10.1016/S0040-4039(01)00309-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2839–2841
Nucleophilic reactions of propargyl acetates mediated by
titanocene dichloride and magnesium
Fanglong Yang, Gang Zhao* and Yu Ding*
Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Lu, Shanghai 200032, PR China
Received 13 October 2000; revised 13 February 2001; accepted 21 February 2001
Abstract—Reaction of Cp2TiCl2/Mg with propargyl acetates form allenyl titanium intermediates, which undergo nucleophilic
addition reactions to aldehydes or ketones to give homopropargyl alcohols in high yields. Subsequent nucleophilic addition to
acetonitrile and nucleophilic substitution with allyl bromide are also mentioned. © 2001 Elsevier Science Ltd. All rights reserved.
The preparation of allenyl and propargyl organometal-
lics and their application in organic synthesis have
drawn much interest in recent years.1 Yamamoto and
co-workers reported the syntheses of propargyl- and
allenyl-titanium intermediates, which were used for the
preparation of allenyl and homopropargyl alcohols,
respectively.2 Sato’s group reported the synthesis of
allenyl and homopropargyl alcohols from propargyl
alcohol derivatives with Ti(O-Pri)4/2iPrMgBr.3 The
preparation and reactions of allenic zirconium species
from propargylic ether derivatives has also been
reported.4 Herein we report a new, efficient and practi-
cal method to produce allenyltitanium intermediates,
which could also be used for the synthesis of allenyl
and homopropargyl alcohols.
good yields. Cp2Ti has been considered as the key
intermediate by us5 in intramolecular Pauson–Khand
reaction of enynes mediated by Cp2TiCl2/Mg. We think
that in the presence of propargyl acetate Cp2Ti could
insert into the triple bond of propargyl acetate to form
an allenyltitanium intermediate which undergoes nucleo-
philic addition to carbonyl compounds as shown in
Scheme 1.
As a potent nucleophile, the allenyltitanium 2 could
also react smoothly with other kinds of electrophiles
such as acetonitrile or allyl bromide to give car-
bonꢀcarbon bond forming products with moderate
yield (entries 2 and 3). The results of nucleophilic
reactions of various propargyl acetate substrates with
electrophiles are shown in Table 1. In contrast to the
poor diastereoselectivity in the reaction of benzalde-
hyde with 2 (entries 9 and 11), the reaction of ring-sat-
Recently, in research directed towards a new car-
bonꢀcarbon bond forming reaction mediated by low-
valent titanium, we found that a low-valent titanium
compound (presumably ‘Cp2Ti’) derived from the reac-
tion of Cp2TiCl2 with 2 equiv. of Mg powder could
react with propargyl acetate to produce an allenyltita-
nium intermediate, which could further react with car-
bonyl compounds to give homopropargyl alcohols in
urated cyclohexyl carboxaldehyde with
2
shows
excellent anti-diastereoselectivity (entry 10). We found
that the reactions of propargyl acetates and its carbon-
ates gave similar yields (entries 1, 4 and 5, 6), even
though propargyl carbonate is usually considered to be
more reactive. It is most interesting to find out that the
Scheme 1.
Keywords: titanocene; homopropargyl alcohol; magnesium.
* Corresponding authors. Tel.: 86-21-64163300; fax: 86-21-64166128; e-mail: dingyu@pub.sioc.ac.cn
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00309-4

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F. Yang et al. / Tetrahedron Letters 42 (2001) 2839–2841
Table 1. The reactions of propargyl acetates with various electrophilesa
reactive low-valent titanium intermediate Cp2Ti could
not be produced in the reaction system of Cp2TiCl2
with BuMgCl, but could be formed only in the pres-
ence of Mg powder. We carried out this reaction
using the Cp2TiCl2/BuMgCl system to replace
Cp2TiCl2/Mg and found out that most propargyl ace-
tate was unchanged; however, when an additional Mg
powder (2 equiv.) was added, the reaction proceeded
smoothly again to form the desired homopropargyl
alcohol. So we think that the possible mechanism
could be as in Scheme 2.
Typical experimental procedure: to a solution of
titanocene dichloride (275 mg, 1.1 mmol) in THF (10
ml) was added the activated Mg powder (2 mmol) at
0°C under an argon atmosphere. After stirring at 0°C
for 1 h, 1 (1 mmol) was added. The resultant mixture
Scheme 2.

F. Yang et al. / Tetrahedron Letters 42 (2001) 2839–2841
2841
was stirred at the same temperature for 6 h. The
aldehyde (1 mmol) was added dropwise to the reaction
mixture at 0°C and then stirred for 2 h. After being
quenched with 10% HCl, the mixture was extracted
with ether. The usual work-up and purification by
column chromatography on silica gel gave the desired
products.6
dimethyl-5-hexenyne, colorless oil, wmax (neat): 3080, 2971,
2225, 1642, 1599, 1489, 1444, 1363, 1070, 997, 915, 755,
691 cm−1; lH (300 MHz, CDCl3) 7.39–7.25 (5H, m, Ph),
5.93–6.08 (1H, m, CH
2.25 (2H, d, 7.2 Hz, CH
6
ꢁCH2), 5.13–5.08 (2H, m, CHꢁCH2
6 ),
6
2), 1.28 (6H, s, 2CH3), lC (75
6
MHz, CDCl3) 135.31, 131.60, 128.13, 127.47, 117.37,
77.24, 76.76, 47.74, 31.48, 29.72, 28.89; m/z (%): 184 (M+,
2.67), 169 (5.82), 143 (100), 128 (35.66), 115 (11.37) 91
(4.10), 77 (6.04), 51 (2.55), 41 (3.77), HRMS calcd for
C14H16: 184.12520; found: 184.12595. 1,4-Diphenyl-
2,2dimethyl-3-butynol, colorless oil, wmax (neat): 3454,
3063, 3033, 2972, 2927, 2225, 1598, 1492, 1384, 1361, 1181,
1046, 1027, 755, 703, 692 cm−1; lH (300 MHz, CDCl3)
7.48–7.26 (10H, m, 2Ph), 4.59 (1H, d, J=4.2 Hz,
In conclusion, Cp2TiCl2/Mg system can be successfully
used to transform readily available propargyl acetates
into allenyltitanium reagents, which could further react
with electrophiles such as aldehydes, ketones and bro-
mides. Thus, we provide a new efficient and practical
method to synthesize homopropargyl alcohols.
PhCH
6
OH), 2.48 (1H, d, J=4.2 Hz, OH
6 ), 1.36 (3H, s,
CH3), 1.20 (3H, s, CH3
6
6
), lC (75 MHz, CDCl3) 140.25,
References
131.63, 128.24, 127.91, 127.85, 127.78, 127.66, 123.42,
94.40, 83.20, 80.58, 38.52, 26.23, 24.88; m/z (%): 250 (M+,
0.4), 233 (8.94), 218 (3.93), 191 (0.77), 144 (92.80), 129
(100), 107 (38.96), 91 (5.72), 79 (34.89), 77, (29.80), 51
(9.44), 41 (4.22). 1,1,2,2-Tetramethyl-4-phenyl-3-butynol,
colorless oil, wmax (neat): 3468, 2978, 2943, 2235, 1599,
1490, 1376, 1138, 756, 691 cm−1; lH (300 MHz, CDCl3)
1. For a recent review, see: Yamamoto, H. In Comprehensive
Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Perga-
mon Press: Oxford, 1991; Vol. 2, pp. 81–98.
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7.41–7.26 (5H, m, Ph), 1.92 (1H, br., OH
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6
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128.23, 127.81, 123.52, 95.43, 82.41, 74.22, 41.37, 25.02,
24.64; m/z (%): 203 (M++1, 0.42), 185 (4.25), 172 (1.31),
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