Alkyne [2 + 2 + 2] Cyclotrimerization Catalyzed by a Low-Valent Titanium Reagent Derived from CpTiX3 (X = Cl, O- i-Pr), Me3SiCl, and Mg or Zn

Article abstract of DOI:10.1021/acs.organomet.8b00678

Inter-, partially intra-, and intramolecular [2 + 2 + 2] cycloadditions of alkynes were catalyzed by a low-valent titanium species generated in situ from the reduction of CpTi(O-i-Pr)₃, CpTiCl₃, or Cp?TiCl₃ with Mg or Zn powder in the presence of Me₃SiCl. The role of Me₃SiCl as an additive in the reaction mechanism is discussed.

Full text of DOI:10.1021/acs.organomet.8b00678

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Alkyne [2 + 2 + 2] Cyclotrimerization Catalyzed by a Low-Valent
Titanium Reagent Derived from CpTiX (X = Cl, O‑i‑Pr), Me SiCl, and
3
3
Mg or Zn
,
†
†
†
†
Sentaro Okamoto,* Takeshi Yamada, Yu-ki Tanabe, and Masaki Sakai
†Department of Materials and Life Chemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686,
Japan
*
S Supporting Information
ABSTRACT: Inter-, partially intra-, and intramolecular [2 + 2 + 2] cycloadditions
of alkynes were catalyzed by a low-valent titanium species generated in situ from the
reduction of CpTi(O-i-Pr) , CpTiCl , or Cp*TiCl with Mg or Zn powder in the
3
3
3
presence of Me SiCl. The role of Me SiCl as an additive in the reaction mechanism
3
3
is discussed.
1
4
INTRODUCTION
Meanwhile, alkyne cyclotrimerization,
which is of
■
importance as a straightforward, atom-economic, synthetically
useful means for synthesizing substituted benzenes, can be also
catalyzed by titanium as well as other early transition metals.
Thus, titanium alkoxides such as calix[4]arene-TiCl com-
plexes, (ArO) TiCl , and a titanium bis(phenolate)-
pyridine complex have been utilized as catalysts or precursors
Low-valent titanium (LVT) reagents, which have been widely
utilized in organic synthesis, can be generated by the reaction
15
1
of TiX (X = halogen, n = 3 or 4) with a reducing agent or, as
n
5
2
more recently reported, from Cp TiCl2 (Cp = η -cyclo-
2
16
17
2
2
penetadienyl) or Ti(OR)4 with an appropriate reductant.
Thus, Cp Ti(III)Cl (and its dimer), Cp TiPh, and Cp Ti(II)-
18
2
2
2
in such reaction. Moreover, a TiCl /i-Bu Al reagent was
4
3
(
L) (L = ligand) can be generated by reduction of Cp TiCl
n 2 2
2,3
19
reported to cyclotrimerize terminal alkynes, and most
recently, cyclotrimerization catalyzed by Ti(II) species derived
from Ti(IV) imido complexes has been developed. Herein,
we report that a LVT species derived from Ti(O-i-Pr) or
CpTiX [X = O-i-Pr, Cl] in the presence of Me SiCl and Mg or
Zn powder can catalyze the inter-, partially intra-, and
intramolecular cyclotrimerizations of alkynes.
with Zn, Na(Hg), Mg, or n-BuLi. Furthermore, the reaction
of Ti(O-i-Pr) or ClTi(O-i-Pr) with an alkyl Grignard or
4
3
20
2
lithium reagent can generate a divalent titanium equivalent (η -
4
4
alkene)Ti(O-i-Pr) . These reagents enable a variety of unique
2
3
3
molecular transformations.
In addition, we have recently reported the generation of
LVTs derived from Ti(O-i-Pr) or titanatrane by the reaction
4
5
with Me SiCl and Mg, along with their synthetic reactions,
3
5
a,f,g
RESULTS AND DISCUSSION
such as C−O bond cleavage of allyl and propargyl ethers
■
5
h
5c
5a,i
and esters, N−S bond cleavage of sulfonamides, reductive
As in our previous report,
Ti(O-i-Pr) catalyzed cyclo-
4
5b
carbonyl coupling (McMurry olefination), imino pinacol
trimerization of terminal alkynes such as 1-hexyne (1a) and
ethynylbenzene (1b) to produce the corresponding trisub-
stituted benzenes in moderate to good yields (entries 1 and 18,
Table 1). In these reactions, the LVT species derived from the
reduction of Ti(O-i-Pr)4 after the ligand exchange from
alkoxide to chloride by Me SiCl is proposed to catalyze the
trimerization of 1-alkynes (eq 1, Scheme1). On the basis of this
hypothesis, we pursued our research on such reactions using
CpTi(O-i-Pr) as a catalyst in the presence of a metal powder
reductant and Me SiCl, where a similar ligand exchange can be
envisaged to promote the generation of an active low-valent
complex (eq 2, Scheme 1). Thus, we found that CpTi(O-i-Pr)3
could catalyze the cycloaddition of 1-hexyne (1a) in the
5
b
5d
5e
coupling, and reduction of epoxides and oxetanes.
On the basis of these results, we pursued further
development of a new LVT and investigated an LVT-
generation method by reduction of half-titanocene trialkoxide
or trichloride CpTiX [X = O-i-Pr, Cl]. Half-titanocenes and
3
3
their derivatives having a modified Cp ligand have been mostly
used as catalysts in the synthesis of polymers from alkenes and
6
,7
lactide. So far, the utilization of CpTiX in organic synthesis
3
3
has been limited to the following examples: (1) LVTs
generated from CpTiCl3 by reduction with Mg(Hg) or
LiAlH4 were reported to promote the reductive pinacol
coupling of aldehydes and ketones. (2) A CpTiCl /LiAlH
reagent deoxygenated 1,4-endoxide compounds to the
3
8
3
4
presence of Mg powder and Me SiCl (entry 3). The addition
3
9
corresponding benzene derivatives. (3) Aromatic halides
were reduced by NaBH in the presence of a CpTiCl
4
3
Special Issue: Organometallic Complexes of Electropositive Ele-
ments for Selective Synthesis
1
0
catalyst. (4) CpTiCl -catalyzed cross-coupling of aryl
3
1
1
fluorides with Grignard reagents. (5) Fluorination of
acetoacetic acid derivatives has been reported. (6) Cyclo-
propanation of nonactivated alkenes have also been reported.
12
Received: September 15, 2018
1
3
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00678
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Table 1. Study on the Reaction Conditions for Alkyne Cyclotrimerization
b
,
c
entry
1
Ti complex (mol %)
metal (equiv)
Me SiCl (equiv)
°C, h
yield (2/3)
3
d
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1c
1c
1d
1d
1d
1d
1d
Ti(O-i-Pr) (10)
Mg (0.5)
Zn (0.5)
Mg (0.5)
Zn (0.5)
Mg (0.5)
Mg (0.5)
Mg (0.5)
Zn (0.5)
Mg (0.5)
Zn (0.5)
Zn (0.5)
Zn (0.5)
Mg (0.5)
Zn (0.5)
Zn (0.5)
Zn (0.5)
Mg (0.5)
Zn (0.5)
Mg (1.0)
Mg (0.5)
Mg (0.5)
Mg (0.5)
Mg (1.0)
Mg (0.5)
Zn (0.5)
Mg (0.5)
Mg (1.0)
(0.5)
(0.5)
(0.5)
(0.5)
40, 12
40, 12
40, 12
40, 12
40, 24
40, 12
40, 12
40, 12
40, 24
40, 24
40, 24
40, 24
40, 24
45, 24
40, 12
40, 24
45, 12
45, 12
40, 12
40, 12
40, 12
40, 12
45, 24
45, 20
45, 24
45, 24
45, 20
71% (41:59)
4
d
Ti(O-i-Pr) (10)
2% (38:62)
4
CpTi(O-i-Pr) (5)
80% (38:62)
70% (40:60)
no reaction
79% (39:61)
trace−38% (39:61)
60% (38:62)
no reaction
3
CpTi(O-i-Pr) (5)
3
CpTi(O-i-Pr) (5)
3
CpTiCl (5)
(0.5)
3
,
ef
CpTiCl (5)
3
g
CpTiCl (5)
Me SiBr (0.5)
3
3
g
CpTiCl (5)
LiCl (0.5)
LiCl (0.5)
3
g
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
CpTiCl (5)
no reaction
no reaction
no reaction
no reaction
3
g
CpTiCl (5)
n-Bu NCl (0.3)
3
4
g
CpTiCl (5)
Ph−Cl (0.5)
MgBr (0.5)
3
g
CpTiCl (5)
3
2
g
CpTiCl (5)
ZnI (0.3)
no reaction
3
2
CpTiCl (5)
(1.0)
80% (38:62)
no reaction
3
CpTiCl (5)
3
Cp*TiCl (5)
(1.0)
(1.0)
(1.0)
(0.5)
(0.5)
(0.5)
(1.0)
(1.0)
(1.0)
(0.5)
(1.0)
68% (38:62)
62% (34:66)
65% (34:66)
3
Cp*TiCl (5)
3
d
Ti(O-i-Pr) (20)
4
CpTiCl (5)
74% (37:63)
63% (30:70)
≤16% (16:84)
3
Ti(O-i-Pr) (10)
4
d
CpTiCl (5)
3
Ti(O-i-Pr) (20)
no reaction
82%
trace
60%
4
CpTi(O-i-Pr) (5)
3
CpTi(O-i-Pr) (5)
3
CpTiCl (5)
3
Cp*TiCl (5)
35%
3
a
The reaction was carried out using an alkyne (1.0 mmol) in THF (2.0 mL). The reactions of entries 2, 7, 22, 26, and 27 were not completed or
did not proceed, and a large or initial amount of alkynes remained unreacted. In all other cases, alkyne 1 was consumed nearly completely, where
b
c
1
oligomeric and/or polymeric materials were coproduced. Total yield of 2 and 3 after column chromatography. Determined by H NMR analysis.
d
e
f
g
See,ref 5a. A large amount of 1 remained unreacted. Not reproducible. Added instead of Me SiCl.
3
Scheme 1. Possible Paths for Generation of LVTs
of Me SiCl proved to be essential for the reaction to proceed
3
(
entry 5). Interestingly, in contrast to the Ti(O-i-Pr)4-
catalyzed reaction, Zn powder could be used instead of Mg
(
entries 2 and 4).
As depicted in eq 3 of Scheme 1, it was expected that
CpTiCl could be reduced by metal powder in the absence of
3
Me SiCl, since no ligand exchange would be required. Indeed,
3
the formation of a CpTiCl −THF complex by reduction of
2
21
CpTiCl with Mg, Zn, or Mn in THF was reported.
3
However, attempts at performing the cyclotrimerization of 1a
with CpTiCl with Mg or Zn in the absence of Me SiCl failed;
3
3
the use of Zn powder resulted in no reaction (entry 16),
whereas the reaction with Mg powder sometimes afforded the
corresponding benzene derivatives, although in low yield and
poor reproducibility (entry 7). These results stem most likely
from the lack of catalytic activity of the in situ generated
Ti(III) species, i.e., CpTiCl −THF complex, in the cyclo-
2
trimerization of alkynes, which may not proceed through a
radical pathway (vide infra).
Nevertheless, surprisingly and delightfully, upon addition of
Me SiCl to the CpTiCl /Mg or CpTiCl /Zn system, catalysis
3
3
3
B
DOI: 10.1021/acs.organomet.8b00678
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Article
proceeded smoothly (entries 6 and 15). Similarly, Cp*TiCl3
Scheme 2. LVT-Catalyzed Inter-, Partially Intra- and
Intramolecular Alkyne Cyclotrimerization Reactions
(
Cp*: pentamethylcyclopentadienyl) with Mg or Zn could
catalyze the cyclotrimerization, albeit in somewhat lower yields
entries 17 and 18). Meanwhile, ethynylbenzene (1b) was
(
cyclotrimerized to triphenylbenzenes by the present system,
with CpTiCl affording better yield than Ti(O-i-Pr) (entries
3
4
1
9 and 20). In contrast, the CpTiCl -catalyzed reaction of
3
ethynyltrimethylsilane (1c) resulted in the inefficient produc-
tion of the corresponding benzene derivative, albeit with better
regioselectivity (entry 22), and Ti(O-i-Pr) was found to be a
4
much better catalyst for the cyclotrimerization of 1c (entry
2
1). These results suggest that the CpTiCl catalytic system
3
might be more sensitive to sterically demanding group(s) than
the reaction with Ti(O-i-Pr) , most likely due to steric
4
repulsion between the Cp ligand and the alkyne substituent.
Besides 1-alkynes, internal alkynes such as 4-octyne (1d)
could be cyclotrimerized by CpTiX /Mg/Me SiCl catalyst
3
3
(
entries 24 and 26), whereas Ti(O-i-Pr) did not catalyze the
4
reaction at all (entry 23). The reaction with Zn instead of Mg
also failed (entry 25). The Cp*TiCl -catalyzed reaction
3
proceeded but resulted in a low yield, due presumably to
steric factors (entry 27).
In summary, 1-alkynes can be cyclotrimerized by Ti(O-i-
Pr) /Mg, CpTi(O-i-Pr) /Mg, CpTiCl /Mg, CpTiCl /Zn, or
4
3
3
3
Cp*TiCl /Mg in the presence of Me SiCl. However, for the
3
3
reaction of 1-alkyne having a sterically demanding substituent
such as trimethylsilyl acetylene, a Ti(O-i-Pr) /Mg catalyst
4
gives better results. The cycloaddition of internal alkynes to
hexa-substituted benzenes requires the use of CpTi(O-i-Pr)3/
Mg or CpTiCl /Mg catalyst.
3
With the CpTiX /Mg or Zn/Me SiCl (X = Cl or O-i-Pr)
3
3
catalytic systems in hand, the substrate scope in the alkyne [2
2 + 2] cycloaddition reactions was investigated, and the
results are summarized in Scheme 2. In addition to 1-alkynes
+
1
1
a, 1b, and 1c, siloxy, benzyloxy, and phenoxy derivatives 1e,
f, and 1g were effectively cyclotrimerized and gave the
corresponding trisubstituted benzenes as a mixture of 1,3,5-
and 1,2,4-isomers in moderate to good yields. In a 20 mmol
scale reaction of 1-hexyne (1a), the reaction with the reduced
amounts of catalyst reagents (2.5 mol %, 45 °C, 36 h)
proceeded smoothly to give a mixture of 2a and 3a in 77%
yield (Scheme 2, 1a with reagents E). Internal alkynes 1d and
Me SiCl is not involved in any redox processes of the
3
22
CpTiCl −metal catalytic system and exists in situ in its initial
3
form. Addition of a halogen ion source such as LiCl, n-Bu NCl,
4
1
h could also be converted to the corresponding hexa-
PhCl, MgBr , and ZnI instead of silyl chloride was found to be
2
2
substituted benzene derivatives by a CpTiCl -catalyzed
ineffective (entries 9−14, Table 1). In contrast, Me SiBr was
3
3
reaction. Besides intermolecular reactions, a CpTiCl /Mg/
effective as well as Me SiCl (entry 8).
3
3
Me SiCl reagent catalyzed partially and fully intramolecular
As shown in the Supporting Information (S-13), CpTiCl3
was reduced by the reaction with Zn powder in THF with a
concomitant change in the reaction mixture color to blue,
3
reactions. Thus, the cross-addition of diyene 1i and 1d (4
equiv) in the presence of the catalyst proceeded to give 4 in
8
5% isolated yield. Meanwhile, triyne 1j was effectively
which could be due to the formation of a CpTiCl −THF
2
21
cyclotrimerized by the catalyst to provide bis-annulated
benzene 5 in 84% isolated yield. These results indicate that
silyl and benzyl ethers, and the ketal functionality were
tolerated under the reaction conditions.
complex, as previously reported in the literatures. However,
the Ti(III) species could not cycloadd alkynes. We previously
reported that titanatrane complex 6 was reduced by Mg
powder in the presence of silyl chloride, and the resulting LVT
species could reduce epoxides and oxetanes through a single
electron transfer process, but the titanium could not effectively
To gain more insight into the role of the silyl chloride
additive in the CpTiCl -catalyzed reaction, a gas chromatog-
3
5e,i
raphy analysis was performed on the reaction mixture (diluted
with hexane) of the CpTiCl /Mg/Me SiCl- or CpTiCl /Zn/
catalyze the cyclotrimerization of triyne 1i (Scheme 3).
From these results, it can be concluded that 6/Me SiCl/Mg
3
3
3
3
Me SiCl-catalyzed 1-hexyne cyclotrimerization. Comparing
might generate the corresponding Ti(III) species selectively,
which was not active for alkyne cyclotrimerization.
3
with authentic samples, it was found that Me Si-SiMe was
3
3
not produced at all. After aqueous workup, the analysis of the
Addition of Me SiCl or 1-hexyne to the CpTiCl /Zn system
3
3
organic layer showed formation of silanol (Me SiOH) and
showed a similar blue color, albeit somewhat darker, and no
product was obtained from 1-hexyne. To test the activation
3
siloxane (Me SiOSiMe ), which were generated by the
3
3
23
reaction of Me SiCl with water. These results suggest that
effect of Me SiCl on Zn or Mg powder, Zn or Mg powder
3
3
C
DOI: 10.1021/acs.organomet.8b00678
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Scheme 3. Results of the Reaction with a Titanatrane
Catalyst
effect of these activations, further reduction of II by metal
powder could take place to generate a lower-valent titanium
species such as complex III. This cooperative activation may
be important because as shown in the above experimental
results adding one of trimethylsilyl chloride and alkyne alone
could not promote the reduction of complexes II′ and II′′.
Subsequently, reduced complex III would undergo oxidative
addition of alkynes to afford titanacylopentadiene V through
IV. Further insertion of alkyne and reductive elimination
would provide the corresponding substituted benzenes.
Furthermore, it can be also proposed that silyl chloride
would have a stabilizing effect for a metastable Ti(II) complex
such as III, which generated in situ by the reductive elimination
of VI, by the coordination of the Cl atom to the titanium
center. The stabilization of the transition-metal complexes with
coordinating chlorosilanes has been reported. Instead of silyl
was treated with Me SiCl in THF and then silyl chloride and
3
the solvent evacuated. In the presence of the pretreated metal
chloride, addition of trimethysilyl triflate (Me SiOTf, 0.5
powder, a mixture of CpTiCl and 1-hexyne did not afford the
3
3
equiv), which is a strong Lewis acid, to 1-hexyne/CpTiCl /Zn
corresponding benzenes. Meanwhile, the mixture of other
3
(
1.0/0.05/0.5 equiv) did not afford the corresponding
coordinative halogen sources, such as LiCl, n-Bu NCl, or PhCl,
4
trisubstituted benzenes, where the reaction mixture turned
brown but the color disappeared immediately. Use of Mg
with CpTiCl /Zn/1-hexyne turned light blue, purple, or blue-
3
26
gray, respectively, and these resulted in no cycloaddition
powder which is stronger reductant than Zn could reduce
reaction (entries 10−12 in Table 1). In contrast, CpTiCl /Zn/
3
CpTiCl −(THF) to a Ti(II) species in the absence of
1
-hexyne was mixed with Me SiCl as well as Me SiBr to turn
2
3
3
Me SiCl, but the reaction gave the corresponding cyclo-
brown and promote the cycloaddition reaction giving
tributylbenzenes (entries 4 and 8 in Table 1). As shown in
the Supporting Information (S12), visible-light absorption
3
trimerization products only in trace to low yields (Table 1,
entry 7), presumably due to lack of the stabilization by silyl
chloride coordination such as complex III. As shown in entry
spectra for the reacting mixture of CpTiCl /Zn with or without
3
1
4 in Table 1, we employed ZnI instead of silyl chloride as an
an additive(s) indicate that only Me SiCl exhibited a different
2
3
additive, which may be expected as an agent to exchange
behavior from other additives. Thus, an addition of Me SiCl to
3
halogen between CpTiCl3 and ZnI . It can generate
CpTiCl /Zn bathochromically shifted the absorption peak
2
3
CpTiI Cl
that may be reduced easier than CpTiCl3.
compared to that of CpTiCl /Zn, while the hypsochromic shift
n
(3‑n)
3
Indeed, adding Zn powder to premixed solution of CpTiCl3
was observed by other additives such as LiCl and n-Bu NCl.
4
and ZnI promoted the reduction and the color turned dark
These results suggest that, in the presence of both Me SiX (X
2
3
blue quickly within a few minutes, which may be a Ti(III)
species. However, the reaction of this mixture with 1-hexyne
did not proceed at all.
=
Cl or Br) and alkyne, CpTiCl could be reduced by Zn in
3
THF to a lower-valent species that would be active for the
cyclotrimerization. On the basis of these results, we propose
the reaction mechanism illustrated in Scheme 4.
CONCLUSION
■
Scheme 4. Proposed Mechanism
We have reported that CpTiX (X = Cl or O-i-Pr) could
catalyze alkyne [2 + 2 + 2] cycloaddition reactions in the
3
presence of Mg or Zn powder and Me SiCl to afford the
3
corresponding substituted benzenes as a mixture of
regioisomers in moderate to good yields. The presence of
Me SiCl proved to be essential for the success of the reaction.
3
Further optimization to avoid the formation of oligomeric
byproducts and control the regioselectivity is underway in our
laboratories.
EXPERIMENTAL SECTION
■
General. NMR spectra were recorded in CDCl at 600 and 500
3
1
13
MHz for H and 150 and 125 MHz for C, respectively, on JEOL
JNM-ECA600 and 500 spectrometers. Chemical shifts are reported in
parts per million (ppm, δ) relative to Me Si (δ 0.00), residual CHCl
4
3
1
13
(
δ 7.26 for H NMR), or CDCl (δ 77.0 for C NMR). IR spectra
3
were recorded on an FT-IR spectrometer (JASCO, FT/IR 4100).
High-resolution mass spectra (HR-MS) were measured on a JEOL
Accu TOF T-100 equipped with an ESI ionization unit. All reactions
sensitive to oxygen and/or moisture were performed under an argon
atmosphere. Dry solvents [tetrahydrofuran (THF) and toluene] were
purchased from Kanto Chemicals. Mg powder (FUJIFILM Wako
Pure Chem. Co., min. 98.0%) and Zn powder (Kanto Chem. Co. Inc.,
min. 90%) were used as purchased. Cyclopentadienyltitanium(IV)
Accordingly, we assume that the alkyne would coordinate to
CpTiCl to form complex II, in which silyl chloride would act
2
as a Lewis acid to coordinate to the Cl atom of CpTiCl . It has
2
been reported that the reduction of Ti(III) to Ti(II) could be
24
promoted by the coordination of π-accepting molecule. It
can be expected that the withdrawal of electron by the silyl
Lewis acid would make the titanium more electron-deficient
trichloride [CpTiCl ] and pentamethylcyclopentadienyltitanium(IV)
3
25
and favored to its reduction. Then, owing to a synergistic
trichloride [Cp*TiCl ] were purchased from Strem Chemicals and
3
D
DOI: 10.1021/acs.organomet.8b00678
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Article
3
0,32
used as they stand. CpTi(O-i-Pr) was prepared by addition of a
tris(trimethylsilyl)benzenes
yield.
(30:70, total 124 mg) in 63% isolated
3
THF-solution of CpTiCl3 to a THF/hexane-solution of i-PrOLi,
generated in situ from i-PrOH and n-BuLi (in hexane) in THF,
1
1,3,5- and 1,2,4-Tris(2-(benxyloxy)ethyl)benzenes (2f and 3f). H
27
according to the modified method in the literature, and the
concentration of the resulting THF(and hexane) solution was
adjusted to 0.1 M by adding an additional THF. The CpTi(O-i-
NMR (500 MHz, CDCl ) δ 7.23−7.33 (m, 15H, Ar), 7.10 (d, J = 6.5
3
Hz, 1H for Ar of 1,2,4-isomer), 7.00−7.04 (m, 2H for Ar of 1,2,4-
isomer), 6.93 (s, 3H for Ar of 1,3,5-isomer), 4.48, 4.49, and 4.50 (3s,
Pr) solution (dark red), in which a part of LiCl was precipitated,
6H, benzylic CH
2
O), 3.60−3.68 (m, 6H, CH
and 2.94 (3t, J = 6.0 Hz, J = 6.0 Hz, J = 6.3 Hz, respectively, total 6H,
CH CH O). C NMR (125 MHz, CDCl ) δ 138.88, 138.39, 138.25,
2 2 3
136.92, 136.83, 134.75, 130.43, 129.82, 128.30, 127.57, 127.48,
127.46, 126.97, 72.93, 72.89, 71.23, 70.94, 36.18, 35.85, 33.07, 32.70.
IR (neat) 3029, 2854, 1602, 1495, 1454, 1361, 1205, 1099, 1027, 734,
CH O), 2.866, 2.874,
2 2
3
could be stored for more than a month under inert atmosphere at
ambient temperature and used as the solution. Other chemicals which
are commercially available, unless otherwise indicated, were used as
1
3
28
29
received. Diyne 1i and triyne 1j were prepared according to the
reported procedures.
−1
+
Structures of the known compounds, i.e., tributylbenzenes (2a and
697 cm . HRMS calcd for C33
H O Na [N + Na ] 503.2557, found
36 3
5
a,29,30,32
5a,30−32
3
(
a),
triphenylbenzenes (2b and 3b),
tri-
503.2566.
30,32
trimethylsilyl)benzenes (2c and 3c),
benzenes (2g and 3g), hexa(n-propyl)benzene (2d), and
,3,6,8-tetrahydrobenzo[1,2-c:3,4-c′]difuran (5),
tri(4-phenoxyphenyl)-
(((2,4,6-Triethylbenzene-1,3,5-triyl)tris(ethane-2,1-diyl))tris(oxy))-
3
1
32
tris(tert-butyldimethylsilane) (2h) and (((3,5,6-Triethylbenzene-
5
a,29,31
1,2,4-triyl)tris(ethane-2,1-diyl))tris(oxy))tris(tert-butyldimethylsi-
1
were con-
1
lane) (3h). H NMR (500 MHz, CDCl ) δ 3.68−3.80 (m, 6H,
3
firmed by comparison of their spectral with those in the literatures
CH O), 2.88−2.95 (m, 6H, CH CH O), 2.63−2.73 (m, 6H,
2
2
2
and/or our authentic samples.
CH CH ), 1.20−30 (m, 9H, CH CH ), 0.93, 0.92, and 0.916 (3s,
2
3
2
3
Typical Procedure for CpTiCl -Catalyzed Cyclotrimerization
3
total 27H, t-Bu), 0.08, 0.07, 0.068, and 0.065 (4s, total 18H, SiCH ).
3
of Alkyne. Under an argon atmosphere, to a mixture of Mg powder
1
3
C NMR (125 MHz, CDCl ) δ 140.58, 139.91, 139.54, 138.95,
33.49, 132.77, 132.34, 131.72, 63.93, 63.81, 33.13, 33.09, 32.98,
2.92, 26.03, 22.73, 22.69, 22.44, 22.40, 18.42, 18.38, 15.58, −5.26,
5.28. IR (neat) 2930, 1471, 1386, 1361, 1254, 1075, 1005, 922, 835,
3
(
24.3 mg, 1.0 mmol) or Zn powder (65.4 mg, 1.0 mmol) in THF (3.0
1
3
mL) was added Me SiCl (126 μL, 1.0 mmol). After being stirred 15
3
min, 1-hexyne (228 μL, 2.0 mmol) and a solution of CpTiCl (1.0
3
−
7
mL, 0.1 M in THF, 0.10 mmol, 5 mol %) were sequentially added.
After being stirred for 12 h at 40 °C, the mixture was poured into a
mixture of aqueous 0.5 M HCl (3 mL) and hexane (6 mL). The
organic layer was separated and the aqueous layer extracted with
hexane (2 × 5 mL). The combined organic layers were dried over
anhydrous Na SO , filtered through a pad of silica gel, and
−
1
+
75, 663 cm . HRMS calcd for C H O Si Na [M + Na ] 659.4682,
36 72 3 3
found 659.4706.
4
′,7′-Dibutyl-2,2-dimethyl-5′,6′-dipropyl-1′,3′-
dihydrospiro[[1,3]dioxane-5,2′-indene] (4). Under an argon
atmosphere, to a mixture of diyene 1i (91.3 mg, 0.30 mmol), alkyne
2
4
1
d (176 μL, 1.2 mmol), and Mg powder (12.1 mg, 0.50 mmol) in
THF (2.0 mL) was added Me SiCl (126 μL, 1.0 mmol). After being
stirred 15 min, a THF solution of CpTiCl (1.0 mL, 0.1 M, 0.10
mmol) was added. After being stirred for 20 h at 45 °C, the mixture
was poured into a mixture of aqueous 0.5 M NaHCO (3 mL) and
Et O (6 mL). The organic layer was separated and aqueous layer
extracted with Et O (2 × 5 mL). The combined organic layers were
dried over anhydrous Na SO , filtered through a pad of Celite, and
concentrated under reduced pressure. The residue was chromato-
graphed on silica gel (hexane/Et O) to isolate 4 (105.5 mg, 85%
yield) and hexapropylbenzene 2d (66 mg).
Compound 4. H NMR (500 MHz, CDCl ) δ 3.77 (s, 4H,
concentrated under reduced pressure. The residue was chromato-
graphed on silica gel (hexane) to give a mixture of 1,3,5 and 1,2,4-
3
5a,29,30,32
3
tributylbenzenes
(39:61, total 130 mg) in 79% isolated yield.
Typical Procedure for CpTi(O-i-Pr) -Catalyzed Cyclotrimeri-
3
3
zation of Alkyne. Under an argon atmosphere, to a mixture of Mg
powder (12.1 mg, 0.5 mmol) and (but-3-yn-1-yloxy)(tert-butyl)-
dimethylsilane (184. mg, 1.0 mmol) in THF (1.5 mL) was added
2
2
2
4
Me SiCl (63 μL, 0.5 mmol). After being stirred 15 min, a solution of
3
CpTi(O-i-Pr) (0.5 mL, 0.1 M in THF, 0.05 mmol, 5 mol %) was
3
2
added. After being stirred for 12 h at 40 °C, the mixture was poured
into a mixture of H O (2 mL) and hexane (3 mL). The organic layer
2
1
3
was separated and aqueous layer extracted with hexane (2 × 3 mL).
CH O), 2.85 (s, 4H, cyclic benzyl CH ), 2.48−2.55 (m, 8H, acyclic
2
2
The combined organic layers were dried over anhydrous Na SO ,
2
4
benzyl CH ), 1.51 (s, 6H, ketal CH ), 1.40−1.55 (m, 12H, CH ),
2
3
2
filtered through a pad of silica gel, and concentrated under reduced
pressure. The residue was chromatographed on silica gel (hexane/
ether) to give a mixture of 1,3,5- and 1,2,4-tris(2-((tert-
butyldimethylsilyl)oxy)ethyl)benzenes (2e and 3e) (39:61, total
1
.06 (t, J = 6.0 Hz, 6H, CH CH ), 0.98 (t, J = 5.5 Hz, 6H, CH CH ).
2 3 2 3
1
3
C NMR (125 MHz, CDCl ) δ 137.49, 137.34, 134.96, 97.81, 69.44,
0.55, 39.38, 32.61, 31.66, 30.36, 25.17, 23.84, 23.42, 15.04, 13.87. IR
neat) 2956, 2870, 1646, 1456, 1381, 1248, 1198, 1156, 1059, 932,
3
4
(
1
46 mg) in 79% isolated yield.
Compounds 2e and 3e. H NMR (500 MHz, CDCl ) δ 7.07 (d, J
−1
1
832, 732, 670 cm . The structure of 4 was confirmed by converting
the corresponding diol, (4,7-dibutyl-5,6-dipropyl-2,3-dihydro-1H-
indene-2,2-diyl)dimethanol, by removal of a ketal moiety (aqueous
HCl−THF, room temperature, 95% yield). (4,7-Dibutyl-5,6-dipropyl-
3
=
1
6.5 Hz, 1H for Ar of 1,2,4-isomer), 6.97−7.00 (m, 2H for Ar of
,2,4-isomer), 6.88 (s, 3H for Ar of 1,3,5-isomer), 3.73−3.80 (m, 6H,
CH O), 2.86−2.90 and 2.75−2.79 (2m, 6H, benzylic), 0.86 and 0.89
2
1
1
3
2,3-dihydro-1H-indene-2,2-diyl)dimethanol: H NMR (500 MHz,
(2s, 27H, t-Bu), 0.002, 0.006, 0.010, and 0.014 (4s, 18H, CH ). C
3
CDCl ) δ 3.77 (s, 4H, OCH ), 2.77 (s, 4H, cyclic CH ), 2.45−2.53
3
2
2
NMR (125 MHz, CDCl ) δ 138.85, 136.90, 134.80, 130.90, 129.99,
3
(
m, 8H, benzylic CH ), 1.37−1.54 (m, 14H, OH and CH ), 1.04 (t, J
2
2
1
2
1
27.81, 127.03, 64.61, 64.33, 64.26, 61.82, 39.53, 39.22, 36.36, 36.03,
13
=
7.5 Hz, 6H, CH ), 0.95 (t, J = 7.0 Hz, 6H, CH ). C NMR (125
3
3
5.94, 25.89, 18.31, −5.27, −5.38. IR (neat) 2928, 2857, 1472, 1386,
−
1
MHz, CDCl ) δ 137.66, 137.31, 134.95, 70.04, 47.54, 37.69, 32.65,
3
255, 1096, 1005, 937, 837, 775, 662 cm . HRMS calcd for
3
2
1.67, 30.40, 25.19, 23.42, 15.06, 13.92. IR (film) 3316, 2954, 2928,
+
C H O Si Na [M + Na ] 575.3743, found 575.3746.
−1
30
60
3
3
869, 1464, 1028, 697 cm . HRMS calcd for C H O Na [M +
2
5
42
2
Typical Procedure for Ti(O-i-Pr) -Catalyzed Cyclotrimeriza-
+
4
Na ] 397.3077, found 397.3078.
tion of Alkyne. Under an argon atmosphere, to a mixture of Mg
powder (24.3 mg, 1.0 mmol) in THF (4.0 mL) was added Me SiCl
3
(126 μL, 1.0 mmol). After being stirred 15 min, ethynyltrimethylsi-
ASSOCIATED CONTENT
■
lane (277 μL, 2.0 mmol) and Ti(O-i-Pr) (59 μL, 0.20 mmol, 10 mol
4
*
S
Supporting Information
%
) were sequentially added. After being stirred for 12 h at 40 °C, the
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00678.
mixture was poured into a mixture of H O (3 mL) and hexane (3
2
mL). The organic layer was separated and aqueous layer extracted
with hexane (2 × 3 mL). The combined organic layers were dried
over anhydrous Na SO , filtered through a pad of silica gel, and
2
4
NMR spectra for compounds 2−5 (PDF). Visible-light
absorption spectra for the reaction mixture (PDF)
concentrated under reduced pressure. The residue was chromato-
graphed on silica gel (hexane) to give a mixture of 1,3,5- and 1,2,4-
E
DOI: 10.1021/acs.organomet.8b00678
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Reagents in Carbohydrate Chemistry: Glycal and C-Glycoside
Synthesis. Tetrahedron 2000, 56, 2103−2112. (h) Yamamoto, Y.;
Hattori, R.; Itoh, K. Highly trans-selective intramolecular pinacol
AUTHOR INFORMATION
Corresponding Author
E-mail for S.O.: okamos10@kanagawa-u.ac.jp.
ORCID
Sentaro Okamoto: 0000-0002-3187-1496
Notes
The authors declare no competing financial interest.
■
*
coupling of dials catalyzed by bulky Cp TiPh. Chem. Commun. 1999,
2
825−826. (i) Yamamoto, Y.; Hattori, R.; Miwa, T.; Nakagai, Y.;
Kubota, T.; Yamamoto, C.; Okamoto, Y.; Itoh, K. Diastereoselective
Inter- and Intramolecular Pinacol Coupling of Aldehydes Promoted
by Monomeric Titanocene(III) Complex Cp TiPh. J. Org. Chem.
2
2001, 66, 3865−3870. (j) Handa, S.; Kachala, M. S.; Lowe, S. R.
Synthesis of N-heterocyclic diols by diastereoselective pinacol
coupling reactions. Tetrahedron Lett. 2004, 45, 253−256. (g) Okamo-
to, S.; Sato, F. Biscyclopentadienyltitanium (III) chloride dimer. e-
EROS Encycl. Reagents Org. Synth. 2002, rn00196.
(3) (a) Takeda, T.; Miura, I.; Horikawa, Y.; Fujiwara, T.
Desulfurizative titanation of allyl sulfides. Regio and diastereoselective
preparation of homoallyl alcohols. Tetrahedron Lett. 1995, 36, 1495−
ACKNOWLEDGMENTS
■
We thank the Ministry of Education, Culture, Sports, Science,
and Technology (MEXT) [no. 17K05869], Japan, for financial
support.
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