Download Carbon-Carbon Bond Formation by Reductive

Carbon-Carbon Bond Formation by Reductive Coupling with Titanium(II)
Chloride Bis(tetrahydrofuran)*
John J. Eisch**, Xian Shi, Jacek Lasota
D epartm ent of Chemistry, The State University of New York at Binghamton,
Binghamton, New York 13902-6000, U.S.A.
Dedicated to Professor Dr. Dr. h. c. mult. Günther Wilke on the occasion o f his 70th birthday
Z. Naturforsch. 50b, 342-350 (1995), received September 20, 1994
Carbon-Carbon Bond Formation, Reductive Coupling, Titanium(II) Chloride,
Oxidative Addition, Carbonyl and Benzylic Halide Substrates
Titanium(II) bis(tetrahydrofuran) 1, generated by the treatm ent of TiCl4 in TH F with two
equivalents of n-butyllithium at -7 8 °C, has been found to form carbon-carbon bonds with
a variety of organic substrates by reductive coupling. Diphenylacetylene is dimerized to ex­
clusively (E,E)-1,2,3,4-tetraphenyl-l,3-butadiene; benzyl bromide and 9-bromofluorene give
their coupled products, bibenzyl and 9,9'-bifluorenyl, as do benzal chloride and benzotrichloride yield the l,2-dichloro-l,2-diphenylethanes and l,l,2,2-tetrachloro-l,2-diphenylethane,
respectively. Styrene oxide and and ris-stilbene oxide undergo deoxygenation to styrene and
fra/«-stilbene, while benzyl alcohol and benzopinacol are coupled to bibenzyl and to a mix­
ture of tetraphenylethylene and 1,1,2,2-tetraphenylethane. Both aliphatic and aromatic ke­
tones are smoothly reductively coupled to a mixture of pinacols and/or olefins in varying
proportions. By a choice of experimental conditions either the pinacol or the olefin could be
made the predom inant product in certain cases. The reaction has been carried out with
heptanal, cyclohexanone, benzonitrile, benzaldehyde, furfural, acetophenone, benzophenone
and 9-fluorenone. In a remarkable, multiple reductive coupling, benzoyl chloride is converted
into 2,3,4,5-tetraphenylfuran in almost 50% yield. The stereochemical course of two such
couplings, that of diphenylacetylene to yield exclusively (E,E)-1,2,3,4-tetraphenyl-l,3-buta­
diene and that of acetophenone to produce only racem/c-2,3-diphenyl-2,3-butanediol, is inter­
preted to conclude that the couplings proceed via two electron transfer pathways (TET)
involving titanium (IV ) cyclic intermediates of the titanirene and the oxatitanacyclopropane
type, respectively.
The monom olecular hydrodeoxygenation or bimolecular reductive coupling of a wide gamut of
organic substrates has been found to occur by the
action of various reactive metals, metal hydrides
or subvalent metal complexes [1,2]. Such reducing
agents often are employed in heterogeneous reac­
tion media either as highly dispersed metal par­
ticles or as metals adsorbed on solid supports such
as graphite. In many other cases, the reducing
agent is generated, in situ, by treating a transition
metal salt with a main group metal, metal hydride
or metal alkyl. Although it is certain that the tran­
sition metal center is thereby reduced, the exact
oxidation state formed is often uncertain and the
role of the main group metal reductant in de­
* XIII Communication of the series, “Organic Chemis­
try of Subvalent Transition Metal Complexes”; XII
Communication: J. Am. Chem. Soc. 108, 7763 (1986).
** Reprint requests to Prof. J. J. Eisch.
0932-0776/95/0300-0342 $06.00
termining the reducing action of the resulting re­
agent is uncertain. The ill-defined nature of such
reductants is readily evident from the numerous
titanium-based reagents reported to be formed
when TiCl4, TiCl3 or CpTiCl2 is treated with,
among others, RLi, RMgX, R3 AI, LiAlH4, Li, K,
Mg or Zn [2], O utstanding among these reducing
combinations for its versatility in organic synthesis
is the McMurry Reagent, a black suspension of
some form of titanium(O) generated when a 4:1
mixture of LiAlH4 and TiCl4 is added to TH F [2],
With this backdrop and in connection with our
investigation of new routes to transition metal
borides [3], we recently found that titanium (II)
chloride could be readily synthesized from titanium (IV) chloride by simply adding two equiv­
alents of a metal alkyl to TiCl4 in toluene or tetrahydrofuran (eqs 1-3 ):
The titanium (II) chloride bis(tetrahydrofuran) 1
formed in eq. 1 could be obtained free of LiCl
and analytically pure by evaporating the TH F and
© 1995 Verlag der Zeitschrift für Naturforschung. All rights reserved.
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J. J. Eisch et al. ■ Carbon-Carbon Bound Formation by Reductive Coupling with TiCl2-2TH F
T i C14
+
TiCl4
+
TiCL
+
2 BunLi
----- — ------►
- 2 LiCl
2 H2C = C H C H ,M g C l
2 Me-iAl
TiCI2-2THF
+
2 BunH
(D
1
— _ u
*L3H6
------------------- ►
- Me2AlCl
■»
TiCl2*2THF*2MgCl2*4rHF
TiCl2*Me2AlCl
+
2 CH4
Results
a) Reaction conditions and stoichiom etry
Reductions with 1 were initially conducted with
the lithium chloride-free reagent in refluxing tolu­
ene or tetrahydrofuran solution. Since the pres­
ence of the LiCl had no marked effect on the re­
ducing activity of 1 for most substrates, subsequent
reductions were carried out directly with the T H F
solutions of 1 still containing the suspended LiCl
(eq. 1). The ratio of 1 to the organic substrate
ranged from 2:1 to 4:1. However, with diaryl k e­
tones, such as benzophenone, failure to remove
the LiCl prior to reduction led to a less active re­
agent [5].
The stoichiometry of one reduction employing
1, which was free of LiCl, is significant: a 1:1 ratio
of 1 and benzophenone 4 gave a 48% yield of
tetraphenylethylene 5 (eq. (4)):
= 0
+
4 T iC l2
--------------- ►
Ph2C = C P h 2
(2)
2
extracting 1 into toluene. The titanium (II) chloride
2 formed in eq. 2 was weakly complexed with the
magnesium chloride by-product and that in equa­
tion 3 formed a stable complex with Me2AlCl 3.
Both 2 and 3, when admixed with an excess of
R„A1C13_„, function as highly active hetero­
geneous Ziegler catalysts for the polym erization of
ethylene and higher olefins, as has been prelim i­
narily reported elsewhere [4].
With a well-defined, soluble subvalent titanium
complex in hand, we were well-positioned to ex­
plore the scope and the mechanism of reduction
of organic substrates by titanium (II) chloride bis(tetrahydrofuran) 1. We report here the results of
our investigation thus far.
2 Ph2C
+
2 C l 2T i — O —
(3)
This observation is consistent with a 2:1 stoichi­
ometry of reaction and the formation of tetrachlorodititanoxane(III) 6.
b) Scope o f organic substrates reducible by 1
(Table I)
a)
Hydrocarbons: Although titanium (II) chlo­
ride in the form of complexes 1, 2 and 3 and ad­
mixed with a six to eight-fold excess of M e2AlCl
is able to catalyze the polymerization of ethylene
and other alpha-olefins [4], complex 1 in TH F or
unsolvated TiCl2 suspended in toluene [6] caused
neither reduction nor oligomerization of such ole­
fins as styrene and 1,1-diphenylethylene, even after
24 h in refluxing solution. Diphenylacetylene 7,
however, underwent a slow bimolecular reduction
to yield solely (E,E)-1,2,3,4-tetraphenyl-l,3-buta­
diene 9 (entry 1 in Table I) upon hydrolysis (eq. 5):
That the organotitanium precursor to 9 is most
likely l,l-dichloro-2,3,4,5-tetraphenyltitanole 8 is
supported by the photoreaction of ?7 3-allyltitanocene 10 with 7, whereby titanole 13 is formed in
60% yield [4]. The reaction mechanism leading to
13 involves the photolytic loss of the allyl radical
from 10 and the generation of titanocene(II) 11.
This undergoes oxidative addition with 7 to pro­
duce titanirene 12, which inserts a further unit of
7 to produce 13 (Scheme 1).
ß) Halides: Aromatic halides and aliphatic ha­
lides, as typified by p-bromoanisole and 1-bromo3-phenylpropane, underwent no discernible re­
duction by 1 during 24 h in refluxing THF. On the
other hand, benzylic halides, such as benzyl bro­
mide 14 gave exclusively the bimolecular re-
T iC l2
(4)
A
4
1
343
5
6
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344
J. J. Eisch et al. • Carbon-Carbon Bound Formation by Reductive Coupling with TiCl2-2TH F
Table I. Reduction of organic substrates with TiCl2-2TH F 1.
Substrate3
Products13
Yield'
1
2
3
Diphenylacetylene3
Benzyl bromide
9-Bromofluorene
4
5
6
7
Benzal chloride
Benzotrichloride
Dichlorodiphenylmethane
Benzopinacol
(E,E)-1,2,3,4-Tetraphenylbutadienee
Bibenzyl
Fluorene
9,9 '-Bifluorenyl
1,2-Dichloro-l ,2-diphenylethanesf
l,l,2,2-Tetrachloro-l,2-diphenylethane
Tetraphenylethylene
Tetraphenylethylene
Tetraphenylethane
Benzophenone
Styrene
rra«s-Stilbeneg
Methyldiphenylamine
Bibenzyl
Benzyl phenyl ketone
7,8-Tetradecanediol
1,1 '-Dihydroxydicyclohexyl dicyclohexylidene
rran5-Stilbeneh
(E)-l,2-Bis(2-furyl)ethane
(E)-2,3-Diphenyl-2-butene
rac-2,3-Diphenyl-2,3-butanediol
(E)-2,3-Diphenyl-2-butene
Tetraphenylethylene
9,9 '-Bifluorenylidene
2,3,4,5-Tetraphenylfuran
14
100
18
82
97
92
96
39
51
10
90
98
15
70
10
80
60
98
95
88
83
13
58
44
47
Entry
8
9
10
11
12
13
14
15
16
17
Styrene oxide
ris-Stilbene oxide
N,N-Diphenylaminomethyl phenyl sulfide
Benzyl alcohol
Benzonitrile
Heptanal
Cyclohexanone
Benzaldehyde
Furfural
Acetophenone
A cetophenone
18
19
20
Benzophenone
9-Fluorenone
Benzoyl chloride
a Unless otherwise specified, all reaction were conducted by allowing a 4:1 m olar ratio of the LiCl-containing
TiCl2 and the organic substrate to reflux in THF solution under an argon atm osphere for 24 h. The individual runs
employed about 2.5 mmol of the substrate dissolved in 30 ml THF; b the product were isolated from the hydrolyzed
reaction mixture by column chromatography and identified by comparing their TLC, GC, m.p. and JH and 13C
NM R spectral properties with those of authentic sam ples;c the yields are those of the isolated components but are
not yet optimized; d a 2:1 ratio of the acetylene to 1 were employed in a 60 h reaction; e a 40 h reaction time was
employed; f a 2:1 ratio of racemic and meso isomers resulted; 8 the ds-isom er was present in 3% yield; h less than
1 % of the c/s-isomer was found.
Ph
T iC l,
Ph
Ph
n
2 P h — C = C — Ph
r
"
^
c/
Ph
H ,0
T r
V
/ " - .P h (5)
P h '-'x
1
H H
V'C1
Sch em e 1
Ph
Ph
Ph
N/
y T\'Cp
Cf
10
12
Ph
Cff
'Cp
13
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J. J. Eisch et al. • Carbon-Carbon Bound Formation by Reductive Coupling with TiCl2-2TH F
duction product, bibenzyl 15 (entry 2 in Table I).
The more hindered 9-bromofluorene 16 provided
82% of 9,9'-bifluorenyl 18, but also 18% of fluorene 17 (eq. 6) (entry 3 in Table I):
16
R
V , * C1
Ph^ NC1
TiCl,
R
Ph— C1— C1— Ph
20: R = H (rac+ m eso)
21: R = Cl
22: R = Cl
JZ\
TiCl,
Cl
Ph
m
I I
Cl Cl
19: R = H
Ph
Ph
^C=C(
Ph
(8)
Ph
23
2 PhCH2OH
TiCI2
-------------►
p\
, ph
P h — C — C — Ph
HO
OH
24
Noteworthy is the inertness of the benzylic
C -C l bonds in 20 and 22 to further reductive elim­
ination and the formation of stilbenes and diphenylacetylene, respectively. By contrast, the pre-
17
Even polyhalobenzylic halides underwent fairly
efficient coupling with 1: a) benzal chloride 19
provided a 2:1 mixture of racemic- and m eso- 1,2dichloro-l,2-diphenylethanes 20 (entry 4 in Ta­
ble I); b) benzotrichloride 21 yielded 1,1,2,2-tetrachloro-l,2-diphenylethane 22 (eq. 7) (entry 5 in
Table I); and c) dichlorodiphenylm ethane 23 pro­
duced tetraphenylethylene 5 (eq. 8) (entry 6 in
Table I):
Ph.
345
PhCH2— CH2Ph
sumed intermediate in eq. 8, 1,2-dichloro-l,1,2,2tetraphenylethane, is readily dechlorinated by 1.
y) Alcohols and ethers: Tetrahydrofuran itself
showed no sign of reductive cleavage to 1-butanol
after 24 h reflux with 1. Ordinary alcohols were
likewise unreactive, although benzyl alcohol was
slowly coupled to produce bibenzyl (entry 11 in
Table I) (eq. 9). Benzpinacol 25 underwent a sig­
nificant amount of beta-bis(dehydroxylation) with
the formation of 5, 25 and 4 (eq. 10) (entry 7 in
Table I).
The significance of the formation of 25 and the
generation of benzophenone 4 will be analyzed
later in the discussion of the mechanisms of TiCl2reductions (cf. infra).
In this class of compounds, epoxides proved to
be the most reactive: Both styrene oxide 26 and
ds-stilbene oxide 27 were readily deoxygenated to
the olefin in high yield (eq. 11) (entries 8 and 9
in Table I):
With 27 it is noteworthy that the deoxygenation
proceeded with high stereoselectivity (29 trans:
cis = 97:3).
(9)
TiCl2
--------- ► Ph2C = C P h 2 + Ph2CH — CHPh2 + Ph2C = 0
5 (39%)
2 5 (5 1 % )
(10)
4 (1 0 % )
19
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346
J. J. Eisch et al. • Carbon-Carbon Bound Formation by Reductive Coupling with TiCl2-2TH F
P .H
ur l/ / , . , - .t___p
\ . i t Hi-iliv-l?R
JC ~
p /
Cv
V RP h '
n‘
/
/ii*
yC — C
-------------------- ►
H
Me
(1 1 )
Me
Ph
J V IC ^
2
TiCli
11V -IJ
___C = 0
J
I ..
^
I I
----------- ►
I
HO
34
26: R = H
w ppL
\
/
X = C V
P h 'Me
Mev
I
Ph— C — C - M e
+
(1 5 )
OH
35
36( 92% )
28: R = H
+ 8 % Z -isom er
27: R = Ph
29: R = Ph
d) Sulfides: As expected, sulfide linkages are
more readily cleaved than ether linkages. How­
ever, their response to 1 is relatively slow. One
such cleavage observed thus far is the following
(eq. 12) (entry 10 in Table I):
T iC l,
Ph2N -C H 2-SPh
Ph2N -C H 3
HS-Ph
(12)
e) Carbonyl derivatives: The great ease of reduc­
ing carbonyl derivatives by 1 is undoubtedly con­
nected with the high oxophilicity of the titanium
in any oxidation state. Because aldehydes, ketones
and acid chlorides are readily reductively coupled
by 1, it should first be noted that carboxylic acids
and esters have proved to be unreactive, and nitriles only slow to reduce. Benzonitrile 30 is slowly
converted to a product that yields benzyl phenyl
ketone 31 upon hydrolysis (eq. 13) (entry 12 in
Table I):
O
II
1 .T iC l2
2
Ph— C = N
P h - C H 2— C — Ph
2. H 20
(1 3 )
31 (10%)
30
Both aldehydes and ketones are reduced by 1 to
give mixtures of the pinacol 32 and the corre­
sponding olefin 33 (Table I) in varying pro­
portions (eq. 14):
R'
'c= o
T iC l,
R
I I
I I
r= c
32
33
R — C — C — R'
HO
(1 4 )
The pinacol 32 or the olefin 33 could in some
cases each be made the predom inant product by
varying the ratio of 1 to the amount of substrate.
Again illustrated with acetophenone, two equiva­
lents of 1 to ketone gave an 83% yield of pinacol
35 while a 4:1 ratio of 1 to ketone produced 88%
of olefin 36. Aliphatic aldehydes and ketones, such
as heptanal and cyclohexanone, gave principally
the pinacol (entries 13 and 14 in Table I). With
aromatic aldehydes, such as benzaldehyde 37 and
furfural 38, little or no pinacol was detected re­
gardless of the proportion of 1 employed (eq. 16)
(entries 15 and 16 in Table I):
A r'
/
(16)
nh
37: Ar = Ph
38: Ar = 2-furyl
As already noted, the LiCl-containing 1 seemed
to be less effective in coupling diaryl ketones.
Even with a great excess of 1, neither benzophenone 4 nor 9-fluorenone gave more than a 4 0 60% yield of the corresponding olefin 33 (entries
18 and 19 in Table I). In fact, much more efficient
coupling to form tetraphenylethylene can be ob­
tained by employing Ph2CCl2 with 1 (eq. 8).
The most rem arkable reductive coupling of a
carbonyl derivative by 1 is that observed with ben­
zoyl chloride 39. The product of this reaction, ob­
tained in almost 50% yield, is 2,3,4,5-tetraphenylfuran 40 (eq. 17) (entry 20 in Table I):
OH
4
II
Ph
Ph
T iC l,
(1 7 )
P h — C — Cl
Ph
W here R and R ' were groups of significantly
different steric demands, the preponderant con­
figurations for the pinacols and olefins formed
were the racemic (32) and the E-configurations
(33), respectively. Thus, in the reduction of acetophenone 34, the pinacol 35 obtained was exclu­
sively the dl-isomer and the olefin 36 was 92% of
the E-configuration (eq. 15) (entry 17 in Table I):
Ar
Nc=c^
a
o
R, R' = H, alkyl, aryl
H
T iC l,
;c = o
39
O
Ph
40
Discussion
The num ber and variety of publications con­
cerning the reduction of organic compounds by
low-valent titanium reagents of ill-defined charac-
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J. J. Eisch et al. • Carbon-Carbon Bound Formation by Reductive Coupling with TiCl2-2THF
ter portray a lively and often bewildering field of
research. The applicability of such reagents in or­
ganic synthesis and their presumed reaction mech­
anisms have been explored by many researchers
and their findings have been ably reviewed and
assessed by Fiirstner [1] and by McMurry [2],
What has impeded more definitive mechanistic in­
sight have been the heterogeneous nature of many
such reductants and the uncertainty about the oxi­
dation states of the active titanium reagents in­
volved. Often, the oxidation state is simply as­
sumed to be Ti(0) or Ti(II) without direct proof.
The coupling of ketones into tetrasubstituted ethylenes by combinations of TiCl4 with zinc dust in
THF is a case in point: a titanium (II) chloride is
assumed to be the reagent, without assurance that
ZnCl2 or Ti(0) might play a role [7],
The previous use of well-defined subvalent ti­
tanium compounds for reductions of organic sub­
strates has been rare. Corey and coworkers have
employed the complex of TiCl2(AlCl3)2 with hexamethylbenzene to form pinacols from ketones [8],
The partly defined complex H T iC 10.5T H F has
been implicated as an active reagent in the
McMurry reaction [9] and the complex,
Ti(MgCl)2 xTHF has also been shown to serve as
a reagent for such ketone couplings [10]. Girolami
and coworkers have employed dimethyltitanium (II) bis(l,2-bisdim ethylphosphinoethane)
for the catalytic dimerization of ethylene to 1-butene 43 [11]. It is thought that this titanium com­
plex 41, for which the crystal structure is known
[12], forms an interm ediate titanacyclopentane by
oxidative addition (eq. 18):
Me
r P/'.. I ..>'p ~ \ h 2c = c h 2
Me
ligand = dmpe
41
>-40 °C
-dmpe
Me
■P,. I
O■P^KI
Me
J
(18)
- 20 °C
- TiMe2 (dmpe)
catalytic
42
43
Whitesides and coworkers dem onstrated that titanocene generated in situ could cyclodimerize
ethylene to produce substantial yields of 45 via 44
[13] (eq. 19):
Cp2TiCl2 ■
2 e'
2cr
[Cp2Ti] H2C=CHV Cp2T i ^
—
O==<0
(19)
In light of these reports, then, the present study
appears to be the first to use a well-defined ti-
347
tanium (II) reagent, 1, containing no additional
Lewis acid (MgCl2, A1C13 or ZnCl2), to achieve
carbon-carbon bond formation with a wide variety
of carbonyl derivatives, benzylic halides, acety­
lenes and epoxides. The presence of exclusively titanium (II) chloride in homogeneous solution
greatly facilitates any detailed investigation of re­
action mechanism.
One of the prime mechanistic questions to be
answered for the reactions of reagent 1 is whether
single-electron transfers (SET) involving exclu­
sively Ti(III) intermediates are involved or whether
concerted two-electron transfers (TET), oxidative
additions leading to titanium(IV) intermediates,
are decisive for such reactions. These possible
pathways are depicted in Scheme 2 with benzophenone.
S ch em e 2
Ph Ph
I I
1 I
TiCl,
Ph— C — C — Ph
2 Ph2C —O — TiCl2
2 Ph2C = 0
Cl2TiO
OTiCl2
TE
Ph Ph
TiCl,
1 I
Ph,C =0
Ph— C — C — Ph
O
Ti
Cl t l
46
Although an unqualified choice between SET
and TET pathways cannot now be made for all of
the organic substrates reacting with 1, stereochem ­
ical evidence for the reactions of 1 with diphenylacetylene (7, eq. 5) and with acetophenone (34,
entry 17, eq. 15) is more consistent with the oper­
ation of a TET or oxidative addition pathway than
SET steps. Were SET operative, the interm ediate
radicals, 47 and 48, should couple for steric rea­
sons and provide the Z,Z-isomer of 9, 49, and the
meso-isomer of 35, 50, respectively (eqs 20 and
21).
Since in fact, only the E,E-isomer 9 and the racemic-isomer 35 are found exclusively in such
couplings, SET processes are inadequate to ratio­
nalize the stereochemical course of reaction.
On the other hand, interm ediate 12 (Scheme 1)
for the acetylene 7 and interm ediate 51 for aceto­
phenone (34, Scheme 3) could be readily be
formed by TET. The resulting rings could undergo
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348
J. J. Eisch et a l ■ Carbon-Carbon Bound Formation by Reductive Coupling with TiCl2 -2THF
2 T iC l,
2
T iC l,
Me Ph
M e.
(20)
2 Ph— C = C .
P h — C = C — Ph
7
Ph
l .C p 2T iC ,H 5
^c= o
2. HiO
HO
34
Ph
C l2T i— C
Ph
2
C — T iC l2
Ph
M?.
^ C — O — T iC l2
34
O TiC l,
► P h - C — C - iP h
/
Ph'
Ph
(2 D
V
C l2T iO
Me
48
m eso-glvcol
SO
Me
Ph'
34
One final observation can be offered in support
of interm ediates like 51 in reactions of ketones
with 1. W hen benzophenone is treated with 1 and
an alcohol or with Ti(BH4)2, significant amount of
1,1,2,2-tetraphenylethane are produced in addition
to tetraphenylethylene [16], We suggest that inter­
m ediate 46 (Scheme 2) undergoes cleavage of its
C -T i bond and the resulting Ph2C H -O T iC l2 un­
dergoes reductive coupling to Ph2CHCHPh2.
These and other mechanistic aspects of the reac­
tions of 1 are receiving our continuing attention.
Experim ental Section
Scheme 3
:c=o
OH
35
/
❖
Me
/C=0
Me
(2 2 )
,C _ C v
49
2
I
I
Ph
\
0
(Z ,Z )-1 ,2 ,3 ,4 -T P B
I
I
Ph— C — C - M e
TiCl,
o—c :".pA c «»Me
- y
yv
cr ci
ph,ve ^ ePh
Ph
//
o
.
'c
/
cr
—C
\
'c i
51
insertion of a second unit of acetylene or ketone
with the ring and the substituents controlling the
stereochemical course of adding the C -T i bond
(Schemes 1 and 3). The second acetylene is
thereby compelled to undergo C -T i bond ad­
dition in a syn-fashion. Similarly, by an approach
of the Si pi-face of 34 to the C -T i bond of 51,
steric repulsion of the approaching Ph and Me
groups is minimized.
Experim ental evidence for such TET processes
and insertions for acetylenes is reported by Alt
and coworkers, who found that Cp2Ti(PMe3)2 re­
acts with acetylene itself to form successively a titanocene like 12 and a titanole like 13 [14], A nal­
ogous evidence for acetophenone was reported by
our group, when we found that titanocene, gener­
ated by the thermal decomposition of ?/3-allyltitanocene in THF, effected the bimolecular reduction
of acetophenone into exclusively the racemic-pinacol 35 (eq. 22). A TET-pathway analogous to that
in Scheme 3 can be deduced from this obser­
vation [15].
General procedures
All procedures involving the purification of re­
action solvents, the preparation of titanium (II)
chloride bis(tetrahydrofuran) 1 and the reactions
of 1 with the various organic substrates were con­
ducted under an atm osphere of anhydrous, oxy­
gen-free argon. The drying and deoxygenating of
argon, as well as of the tetrahydrofuran and the
toluene used in reactions of 1, were carried out
according to established procedures [17].
Instrumentation and analyses
All melting points were measured with a
Thom as-Hoover capillary melting point apparatus
and are uncorrected. Infrared spectra (IR) were
recorded on Perkin-Elm er spectrophotom eters.
Models 457 and 283 B, which were equipped with
sodium chloride optics. Nuclear magnetic reso­
nance spectra (!H and 13C NM R) were obtained
with a Bruker spectrometer, Model AM-360, on
pure samples or as 10% solutions in pure deuteriated solvents. The 'H NM R data were reported on
the <5 scale in parts per million with reference to
internal tetramethylsilane. Mass spectral data
were collected with a Hewlett-Packard gas chro­
matograph-mass spectrometer. Model 5882 B.
Gas-liquid phase chromatographic analyses (GC)
were carried out with an F&M tem perature-pro­
grammed chrom atograph. Model 720, equipped
with dual 12-ft column of a 10% UC-298 phase on
a Chromosorb W support and with an electronic
peak-area integrator. Thin-layer chromatographic
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J. J. Eisch et al. • Carbon-Carbon Bound Formation by Reductive Coupling with TiCl2~2THF
analyses (TLC) were done on Eastman Chromagram Sheets, no. 13181, consisting of silica gel with
fluorescent indicator. Analyses of 1 were
conducted on vacuum-dried samples in the follow­
ing ways: 1) the dihydrogen evolved from hy­
drolyzed samples was collected and m easured; 2)
the tetrahydrofuran liberated by such hydrolysis
was extracted and analyzed by GC for any content
of 1-butanol; 3) the titanium (III) ion generated by
such hydrolysis was oxidized by H 20 2 to titanium(IV) ion and the latter ion was determ ined
by a complexometric titration with the m onosod­
ium salt of ethylenediaminetetraacetic acid (Complexon III); and 4) the chloride ion in hydrolyzed
samples was determ ined by the Volhard method.
Preparation o f titanium(II) chloride
bis (tetrahydrofuran) 1
To 250 ml of anhydrous THF cooled to -7 8 °C
(solid C 0 2-acetone bath) were slowly added 40 ml
of a 1.0 M solution of TiCl4 in toluene. A fter 1 h
of stirring at -7 8 °C a bright yellow solid suspen­
sion had formed. Then over 2 h 32 ml of a 2.5 M
solution of «-butyllithium in hexane was gradually
introduced as the suspension successively turned
yellow-green and then light brown. The reaction
mixture was thereafter brought to room tem pera­
ture and stirred for 18 h. At this point a black solu­
tion with suspended LiCl had formed. The reagent
1 formed at this point was employed directly for
the reactions reported in this article.
Analytical samples of 1 could be obtained by
removing much of the THF under reduced pres­
sure at 25 °C. Filtration of the black suspension
under argon and washing the filter residue with
toluene gave >95% of gray LiCl. The filtrate was
then evaporated to dryness in vacuo and solid resi­
due washed slowly on the filter with portions of
a 1:1 (v/v) THF-toluene mixture. The black filter
residue was dried in vacuo to yield 95% of essen­
tially pure 1.
Anal. Calcd for C8Cl2H 160 2Ti: Ti, 18.21; Cl,
26.96; evolved H 2, 0.5 mol; ratio of T :C1, 1.0:2.0;
Calcd for C4Cl2H 8OTi: Ti, 25.09; Cl, 37.14.
Samples of 1 prepared in the following m anner
gave the following analyses: Ti, 19.8, Cl, 30.0, ev­
olved H2, 0.45 mol; ratio of Ti:Cl, 1:2.05. These
values correspond to TiCl2-1.75 THF. A lterna­
tively, samples of 1 could be obtained from the
original reaction mixture by complete removal of
all the THF and toluene at 30 °C in vacuo to pro­
duce a gray-black solid residue. The residue was
then stirred with 150 ml of a 1:1 (v/v) mixture of
THF and toluene for 1 h and the suspension then
349
filtered from the LiCl. The black filtrate was
evaporated to form the TiCl2 residue. A fter drying
for 3.5 h in vacuo the black solid was found to con­
tain 23.53% Ti and 34.76% Cl; ratio of Ti:Cl,
1.0:2.00.
These
values
correspond
to
TiCl2-1.2 THF. From these analytical values we
conclude that titanium (II) chloride in TH F solu­
tion exists as the bis(tetrahydrofuran) but that in
the solid state one THF unit is labile to dis­
sociation.
To assure ourselves that the coordinated THF
was not actually an n-butoxy group bonded to Ti
and possibly formed by reductive cleavage, a
sample of 1 was hydrolyzed and the evolved THF
analyzed by GC. The THF was found to contain
<2% of 1-butanol.
Typical procedures fo r the reactions o f lithium
chloride-containing titanium(II) chloride
bis (tetrahydrofuran) 1: trans-Stilbene
from benzaldehyde
Since all the reactions were conducted in an
analogous m anner and formed products which are
known, well-characterized compounds, the follow­
ing procedure should suffice to illustrate the ap­
propriate experimental operations.
To a solution of TiCl2-2TH F 1 (10 mmol) in
TH F (30 ml) at 25 °C was added freshly distilled
benzaldehyde (265 mg, 0.25 ml, 2.5 mmol). The
resulting reaction mixture was heated under reflux
for 24 h, quenched with H20 (100 ml), and filtered
through a Celite cake. The Celite cake was washed
twice with E t20 (2x25 ml). The aqueous layer was
then extracted with E t20 (2x25 ml) and the com ­
bined organic extracts dried over anhydrous
M gS 04. The extracts were then freed of solvents
on a rotatory evaporator and the crude product
was purified by flash column chromatography
(eluent hexanes/THF 50:1) to give 220 mg of
frans-stilbene as a white crystal. M.p. 120-121 °C
(lit. 122-124 °C). 'H NM R (CDC13) (3 (in ppm):
7.48 (d, 4H ), 7.32 (t, 4H ), 7.22 (t, 2H ), 7.08 (s,
2H ); 13C NM R (CDC13) (3 (in ppm): 137.36,
128.71, 128.65, 127.58, 126.51. This product con­
tained < 1% of ds-stilbene.
Acknowledgem ents
This research was initiated under a m aterial sci­
ence project sponsored by Akzo Corporate R e­
search America Inc., continued under support by
the U.S. National Science Foundation G rant CHE87-14911 and brought to fruition with funding
from Solway & Cie, Brussels, Belgium. We are in-
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Download Date | 6/15/17 6:23 PM
350
J. J. Eisch et al. ■ Carbon-Carbon Bound Formation by Reductive Coupling with TiCl2-2TH F
debted to Dr. S. L. Pombrik for assistance in im­
proving the preparation of titanium (II) chloride as
the TH F complex 1 and as the 1:1 complex with
M e2AlCl 3.
[1] A. Fiirstner, Angew. Chem., Int. Ed. Engl. 32, 164
(1993).
[2] J. E. McMurry, Chem. Rev. 89, 1513 (1989).
[3] J. J. Eisch, J. Lasota, S. L. Pombrik, “Novel Route to
Titanium Bis(borohydride) and its use as a Precur­
sor to Titanium Dichloride”, Invention Disclosure
No. R-920, Dec 3, 1991, The Research Foundation
of the State University of New York, U.S.A.
[4] J. J. Eisch, S. L. Pombrik, X. Shi, S.-C. Wu, Macromolecular Symposia, in press.
[5] The retarding effect of LiCl on the reducing action
of 1 with diaryl ketones may stem from complexation to form LiTiCl3 intermediates, but this as­
pect merits further study.
[6] We are currently investigating the reducing ef­
ficiency of TiCl2 generated by treatm ent of TiCl4 in
toluene directly with «-butyllithium in hexane.
[7] D. Lenoir, Synthesis 8, 553 (1977).
[8] E. J. Corey, R. L. Dansheiser, S. Chandrasekaran. J.
Org. Chem. 41, 260 (1976).
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[11] M. D. Spenser, P. M. Morse, S. P. Wilson, G. S. Girolami, J. Am. Chem. Soc. 115, 2057 (1993).
[12] J. A. Jensen, S. R. Wilson, A. J. Schultz, G. S. Girolami, J. Am. Chem. Soc. 109, 8094 (1987).
[13] J. X. M cDermott, M. E. Wilson, G. M. Whitesides, J.
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[14] H. G. Alt, H. E. Engelhardt, M. D. Rausch, L. B.
Kool, J. Am. Chem. Soc. 107, 3716 (1985).
[15] J. J. Eisch, M. E. Boleslawski, J. Organomet. Chem.
334, C l (1987).
[16] J. J. Eisch, S. L. Pombrik, X. Shi, unpublished
studies.
[17] J. J. Eisch, Organometallic Synthesis, Vol. 2, pp. 7 25, Academic Press, New York (1981).
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