First synthesis of metallated titanacyclopropenes

Article abstract of DOI:10.1055/s-1999-2964

A novel and efficient one-pot synthesis of trismetallated olefins is described by using the diisopropyloxy(η²-propene)titanium derivative.

Full text of DOI:10.1055/s-1999-2964

LETTER
1939
First Synthesis of Metallated Titanacyclopropenes
Claudia Averbuj, Julia Kaftanov, Ilan Marek*
Department of Chemistry and Institute of Catalysis Science and Technology
Technion-Israel Institute of Technology, Technion City, Haifa 32000 Israel
Fax:972 4 823 37 35
E-mail: chilanm@tx.technion.ac.il
Received 23 August 1999
Dedicated fondly to Professor L. Ghosez on the occasion of his 65th birthday.
Et2O
iPrO
iPrO
iPrO
iPrO
Abstract A novel and efficient one-pot synthesis of trismetallated
olefins is described by using the diisopropyloxy(h -propene)titani-
um derivative.
Ti(OiPr)4 + 2 iPrMgBr
Ti
Ti
2
-
78°C 30 mn
then -50°C 30 min
1
Key words: metallated titanacyclopropenes, titanium(II), bismetal-
lic, alkynes, alkenes
nBuLi
Et O
MXn
M
Oct
H
Oct
Li
Oct
M
2
Oct
1
+
Oct
3
H O
The synthesis of polysubstituted olefins in a single-pot
operation from common starting material is still the object
of continuing vigorous research . Among several strate-
-78°C
then -50°C
Ti
PrOi
OiPr
1
Scheme 1
gies, the synthesis and reactivity of 1,1-dimetalloalkenes
2
with a large variety of metals (dilithium , aluminum and
3
3
4
titanium , aluminum and zirconium , zinc and zirconium ,
5
5
zinc and boron , copper and boron , copper and
zirconium , lithium and boron , zinc and zinc and finally
boron and zirconium ) were used as a source of tri- and
metal and on the experimental conditions. Indeed, starting
from alkynyllithium (M = Li) or alkynylmagnesium bro-
mide (M = MgBr), the desired product was not obtained
in the former case and only in 20% yield in the latter one.
The best cases were the alkynyltitanium triisopropoxide
4
6
7
8
tetra-substituted olefins. In this context, we have already
reported the allylmetallation of alkynyl metals leading to
9
2
10
sp 1,1-bismetallic derivatives in good overall yield .
These geminate bis-anions react selectively with two dif-
(
M = Ti(OiPr) , 41% yield) and either the alkynylzinc
3
bromide (M = ZnBr, 65% yield) or alkynyl-alkylzinc
M = ZnBu, 68% yield). Unfortunately, even in these last
1
0
ferent electrophiles and can be a source of chiral a,a’-
(
1
0c
disubstituted alkynes . However, in the course of our
studies on the synthesis and reactivity of polymetallated
alkenes, we needed a more general preparation of these re-
agents allowing the access to a variety of carbon skele-
tons. Our attention was drawn by the pioneering work of
Sato et al who demonstrated that various disubstituted
three cases, it was very difficult in our hands to get repro-
ducible results (i.e. for the alkynylzinc bromide the yield
was varying from 25% to 70%). These fluctuations were
attributed to the possible instability of the preformed low-
valent titanium alkoxide 1 under these Grignard-type ex-
17
perimental conditions , and also to the rearrangement of
2
alkynes react with diisopropyloxy(h -propene)titanium
18
1
into the corresponding cyclic product 2 . These results
1
1
1
, readily generated by the reaction of Ti(OiPr) with 2
4
strongly suggest that we have a competing reaction of 1;
formation of the desired product or formation of 2. In-
deed, bromination of the reaction mixture instead of hy-
drolysis gave (D,L)-1,4-dibromo-2,3-dimethylbutane
selectively in variable chemical yields (the balance being
the product of the reaction of the metallated titanacyclo-
equiv. of iPrMgX, to give the corresponding titanacyclo-
propene derivatives. Although terminal alkynes failed to
participate in the present reaction, the use of this low-
valent titanium alkoxide reagent was successfully applied
12
to several systems . The same type of intermediate as 1
had previously been used for the synthesis of
propene with Br2).
1
3,14
15
cyclopropanols
and cyclopropylamines . Inspired
by this work, we were pleased to find that the ligand
exchange of the low-valent titanium alkoxide can be
1
6
iPrO
iPrO
iPrO
iPrO
performed with a metallated alkyne to give the corre-
sponding metallated titanacyclopropene. Our initial at-
tempts consisted in adding alkynyl metal derivatives to
Ti
Br2
Br
Ti
Br
1
2
II
the preformed Ti complex 1 (Scheme 1).
Equation 1
However, this new strategy was only moderately success-
ful since the overall chemical yield of the polymetallated
olefin was strongly dependent on the nature of the alkynyl
Synlett 1999, No. 12, 1939–1941 ISSN 0936-5214 © Thieme Stuttgart · New York

1
940
C. Averbuj et al.
LETTER
In order to overcome these chemical yield variations as
well as to avoid the formation of 2 it was necessary to find
new experimental conditions in which the diisopropy-
2
loxy(h -propene)titanium 1 would be generated in the
1
7
presence of the electrophile (Barbier Conditions) .
For this purpose, we found after several experiments19
that treatment of chloroalkyne 3 (Scheme 2, R = alkyl,
X = Cl) with 2.5 equivalents of the combination
Ti(OiPr) /iPrMgBr (in a 1:2.5 ratio) gives, in a single-pot
4
operation at –50 °C in 2 hours, the desired titano-titana-
cyclopropene 6 in high chemical yield (Scheme 2).
R
X
Et2O
R
X
+
Ti(OiPr)4
iPrMgBr
Ti
case of the alkynyl thiophenyl ether (entry 4), a good
chemical yield was obtained.
-
78°C to
3
-
78°C
iPrO
OiPr
-
50°C
R = Alkyl X = Cl
4
MeOD
Path A
On the other hand, further investigations revealed interest-
ing reactivities of zirconocene-(1-butene) 16 and ti-
tanocene-(1-butene) 17 derivatives with a chloroalkyne.
Indeed, whereas the reaction of 1623 with ptolylchloro-
acetylene (see Scheme 3) afforded the corresponding tris-
metallated olefin 18 in high yield (91% after hydrolysis),
9
3%
R
D
R
TiX(OiPr)2
%D> 95
5
1
R
H O+
3
R = Oct
0%
Path B
R
TiX(OiPr)2
9
7
24
the same reaction with Cp Ti-(1-butene) 17 lead only to
R
D
D
Ti
2
R = Oct
7%
D>95
MeOD
iPrO
OiPr
25
8
15% of 19 . When the same strategy is applied to 3
D
%
6
8
(R = alkyl) either with 16 or 17 only low conversions to
2
6
trimetallated olefins are obtained .
Scheme 2
THF
Cp2MCl2
+
2 nBuLi
Cp MBu
2
Cp M
2
2
A plausible mechanism for this reaction is shown in
-78°C
2
Scheme 2. The in situ formed diisopropyloxy(h -pro-
Et
M = Zr 16
M = Ti 17
M = Ti, Zr
pene) titanium 1 (generated as described in Scheme 1) re-
1
1
acts with chloroalkyne 3, via a ligand exchange , to give
ptolyl
M(Cl)Cp2
2
0
H3O+
as an unstable intermediate the chloro-titanacyclopro-
ptolyl
pene 4 (R = alkyl, X = Cl). Then, 4 undergoes a very fast
M
ptolyl
Cl
1
8 M = Zr 91%
2
1
Cp
Cp
b-elimination at low temperature to give the alkynyltita-
19 M = Ti 15%
2
2
nium derivative 5 . Quenching the reaction with MeOD
at –78 °C proved the presence of the metallated alkyne 5
since the deuteroalkyne (Scheme 2, path A) was quantita-
tively obtained. When the reaction mixture is warmed to
Scheme 3
2
In conclusion, the use of diisopropyloxy(h -propene)tita-
nium 1 provides an efficient one-pot method for synthe-
sizing trimetallated olefins from common starting
materials . It should be noted that whereas terminal
alkynes failed in the present reaction , it occurs very
nicely with a metallated alkyne and then the alkynyl orga-
nometallic behaves like a carbon center. Synthetic appli-
cations of the present methodology and investigations to
–
50 °C and stirred for 2 hours, the second equiv. of 1 can
react with 5 to give quantitatively the titano-titanacyclo-
propene 6 (Scheme 2, path B). After hydrolysis, 7 is iso-
lated in high yield. The presence of 3 carbon-metal bonds
was proven by reaction with MeOD to give 8 (>95%D in
27
11
8
7% yield). Results for a variety of alkynes are shown in
the Table. In all cases, only the polymetallated species
was obtained, whatever the nature of the R group.
28
confirm the mechanistic rationale of the reaction are
Indeed, several chloroalkynes with an alkyl, phenyl or ho- now in progress in our laboratory.
mopropargylic ether group lead to the products in good to
high yields (entries 1, 5 and 6). Interestingly, according to
Acknowledgement
the nature of the leaving group, minor variations in the
chemical yields are observed (compare entries 1, 2 and 3). I.M. is the Holder of the Lawrence G. Horowitz Career Develop-
ment Chair, is a Ygal Alon fellow and Evelyn and Salman Grand
Academic Lectureship-USA. This research was supported in part by
The Israel Science Foundation founded by The Academy of Sci-
ences and Humanities (N° 060-471) and by the fund for the promo-
Whereas the first step is still quantitative (formation of the
metallated alkyne 5), the second one is dependent on the
nature of the halogen X on alkynyltitanium 5. Even in the
tion of research at the Technion. Acknowledgment is also made to
Synlett 1999, No. 12, 1939–1941 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
First Synthesis of Metallated Titanacyclopropenes
1941
the donors of The Petroleum Research Fund, administered by the
ACS, for partial support of this research (PRF#33747-AC1). The
authors thank also P. and E. Nathan Research Fund, N. Haar and R.
Zinn Research Fund. J.K. thanks the ministry of Immigrant Absorp-
tion for financial support.
(16) Titanation of alkynyltin was already described, see: V.
Launay, I. Baudet, J.P. Quintard, Synlett 1997, 821 and more
recently, see ref. 12a. Zirconium mediated intramolecular
coupling of terminal alkynes was also published J. Barluenga,
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17) Grignard Conditions (formation of the organometallic
derivative and then introduction of the electrophile) as
compared to Barbier Conditions (formation of the
organometallic derivative in the presence of the electrophile).
18) This rearrangement was already reported for zirconocene
derivatives; T. Takahashi, T. Fujimori, T. Seki, M. Saburi, Y.
Uchida, C. J. Rousset, E. I. Negishi, J. Chem. Soc., Chem.
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(
(
(
References and Notes
(
1) a) I. Marek, J.F. Normant, Carbometallation Reactions in
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(
(
(
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bromide and Ti(OiPr) in Et O at –78 °C did not give the
4
2
expected product but more probably the zincate. The
transmetallation between iPrMgBr and the alkynylzinc
bromide is faster than the reaction between the same Grignard
reagent and Ti(OiPr)4.
1
276. b) E.I Negishi, Pure and Appl. Chem. 1981, 53, 2333.
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(
20) All attempts to trap the intermediate 4 at low temperature were
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(
(
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(
(
(
(
1
II
via an oxidative addition of the Ti into the chloroalkyne.
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3
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(
(
(
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25) The balance being the starting material (21%) and the metallo-
alkyne (65%)
26) Whereas with 16 40% of the polymetallated olefin can be
obtained (accompanied by the formation of high molecular
weight products), the use of 17 gave only 10% of the desired
metallated double bond (the major product being the starting
material)
(
2
73, 1669. b) Y. Frangin, M. Gaudemar, Compt. Rend. Acad.
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(
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(
27) Representative experimental procedure: To a stirred solution
3203.
of 1-chloro-1-decyne (300 mg, 1.7 mmol) and Ti(O-iPr) (1.3
4
(
12) For recent papers a) H. Urabe, T. Hamada, F. Sato, J. Am.
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mL, 4.3 mmol) in 20 mL of Et O was added a 1.1 M solution
2
of iPrMgBr in ether (7.8 mL, 8.58 mmol) at –78 °C under
argon to give a yellow homogeneous solution. The solution
was warmed to –50 °C over 30 min, during which period its
color turned brown. After stirring at –50 °C for an additional
(
13) a) O. G. Kulinkovich, S.V. Sviridov, T.S. Vasilevski, T.S.
Pritskaya, Zh. Org. Khim. 1989, 25, 2245. b) O. G.
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D.A. Vasilevski Synthesis 1991, 234, and references cited
therein.
2
h, a 1M solution of HCl was added. The organic phases were
extracted twice with a 1M aqueous solution of HCl and the
aqueous phases were washed with ether. The combined
organic phases were dried over MgSO and concentrated in
4
vacuo to give a crude oil. Purification by chromatography
(
silica gel, hexane) afforded decene in 90% yield.
(
14) a) J. Lee, J.D. Ha, J.K. Cha, J. Am. Chem. Soc. 1997, 119,
(
28) Until now, all our attempts to get crystals for X-Ray structure
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8
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8
(
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1
Synlett 1999, No. 12, 1939–1941 ISSN 0936-5214 © Thieme Stuttgart · New York