McMurry coupling of aryl aldehydes and imino pinacol coupling mediated by Ti(O-i-Pr)4/Me3SiCl/Mg reagent

Article abstract of DOI:10.1016/j.tetlet.2009.11.027

Ti(O-i-Pr)₄/Me₃SiCl/Mg reagent mediated McMurry coupling of aryl aldehydes to biaryl olefins at near room temperature. This low valent titanium (LVT) reagent also mediated the coupling of aldimines to 1,2-diamines (imino pinacol coupling).

Full text of DOI:10.1016/j.tetlet.2009.11.027

Tetrahedron Letters 51 (2010) 387–390
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Tetrahedron Letters
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McMurry coupling of aryl aldehydes and imino pinacol coupling mediated
by Ti(O-i-Pr)4/Me3SiCl/Mg reagent
*
Sentaro Okamoto , Jing-Qian He, Chihaya Ohno, Yuhji Oh-iwa, Yuhki Kawaguchi
Department of Material & Life Chemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Ti(O-i-Pr)4/Me3SiCl/Mg reagent mediated McMurry coupling of aryl aldehydes to biaryl olefins at near
room temperature. This low valent titanium (LVT) reagent also mediated the coupling of aldimines to
1,2-diamines (imino pinacol coupling).
Received 30 October 2009
Accepted 9 November 2009
Available online 12 November 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Low valent titanium (LVT) reagents have gained widespread
acceptance in organic synthesis.1 Besides well-defined LVT re-
agents such as TiX3, Cp2TiCl (or its dimer), their aggregates, and
solvated derivatives, LVT reagents generated in situ from TiCl4 or
TiCl3 by the reaction with various reducing agents have been uti-
lized for a variety of reactions, in which active species is still under
debate. Reactivity of the in situ-prepared LVT reagents, including
reaction course, reproducibility, chemoselectivity, and stereo-
chemistry, varies greatly with the source of the titanium metal
and reducing agent, its procedure for preparation, and the experi-
mental conditions involving the presence of an additional control-
ling agent (additive).1,2 Many studies have focused on the ability of
the large variety of LVT reagents to mediate the reductive coupling/
deoxygenation of carbonyl compounds, known as McMurry cou-
pling,1a–g which is one of the most widely utilized synthetic reac-
tions. Conventionally, such LVT reagents have been prepared
using Rieke’s method involving reduction of TiCl4 or TiCl3 with
an alkali metal (Li, Na, or K) in an ethereal or hydrocarbon solvent.
These reagents, in general, are prepared prior to the reaction with
the substrate(s) and the protocol yields usually heterogeneous col-
loidal slurries of activated titanium. At low temperature, the reac-
tion of carbonyl compounds with the LVTs gives the corresponding
titanium pinacolates. The extrusion of oxygen from the pinacolates
to olefins necessitates the conditions of solvent-reflux temperature
and prolonged reaction time. In addition to the intricateness of
procedure, the functional incompatibility under the refluxing con-
ditions restricts the utility of LVT reagents.
this combination of reagents Ti(O-i-Pr)4/MCln/Mg through the fol-
lowing reaction pathway: (i) titanium i-propoxide reacts with hal-
ogen source compound to afford a titanium chloride compound(s)
and i-PrOMClnꢀ1, (ii) the resulting titanium chloride(s) can be re-
duced by the reaction with Mg to generate a lower valent species,
(iii) these processes may be repeated with the gradual generation
of Ti(III) and lower valent titanium species. As a result, the system
generates LVT reagents under mild conditions and the reaction
mixture remains homogeneous, except for the Mg powder, to all
appearances.
Now we wish to report that a Ti(O-i-Pr)4/Me3SiCl/Mg reagent
mediates McMurry coupling2,4 of aryl aldehydes 1 to biaryl olefins
at near room temperature and the reagent also couples aldimines 2
to 1,2-diamines (imino pinacol coupling)5 (Eq. 4 in Scheme 1).
Application of McMurry coupling with the LVT to the polymeriza-
Recently, we have reported that treatment of Ti(O-i-Pr)4 with
Mg powder in the presence of a halogen source such as R3SiCl
and MgCl2 in THF generates a specific LVT species at room temper-
ature, which catalyzes alkyne [2+2+2] cycloaddition reactions and
C–O bond-cleaving reaction of allyl and propargyl ethers (Eqs. 1–3
in Scheme 1).3 We showed that a LVT(s) could be generated from
* Corresponding author. Tel.: +81 45 481 5661; fax: +81 45 413 9770.
E-mail address: okamos10@kanagawa-u.ac.jp (S. Okamoto).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.11.027

388
S. Okamoto et al. / Tetrahedron Letters 51 (2010) 387–390
tion reaction starting from di-carbonyl compounds is also
disclosed.
production of diol 4a. Among them, the reaction in the presence
of Et3N (2.6 equiv) at 40 °C yielded 3a in 97% NMR yield with a high
E-selectivity, whereas co-production of 4a was minimized to be
only 2% (run 11).
Table 2 summarizes the results of the reductive coupling of var-
ious aryl aldehydes with Ti(O-i-Pr)4/Me3SiCl/Mg/Et3N reagent. The
reactions afforded 1,2-diarylethylenes predominantly in moderate
to good yields. The reaction of benzaldehyde (1b) as well as aryl
aldehydes 1a, 1d, 1e, and 1g with an electron-donating group
showed good selectivity. However, aldehydes with an electron-
deficient group such as 1c and those with a coordinating group
around the carbonyl moiety such as 1f, 1h, and 1i reacted slowly
Table 1 summarizes the results of optimization of a Ti(O-i-Pr)4/
Me3SiCl/Mg-mediated reductive coupling of aryl aldehyde 1a. In
the absence of Ti(O-i-Pr)4 or Me3SiCl, the reaction did not take
place (runs 1 and 2). The reaction with stoichiometric amounts
of Ti(O-i-Pr)4 and Me3SiCl proceeded to give 1,2-diarylethylene
3a, but the reaction at room temperature was slow (run 5). The
reaction proceeded with a reasonable rate at 40 °C to provide 3a
in 76% NMR yield, but a large amount of 1,2-diol 4a was also pro-
duced (run 6). When the effect of additives was studied (runs 7–
11), it was found that the addition of a Lewis base decreased the
Table 1a
Run
Tib equiv
SiClc equiv
Additive equiv
°C/h
Products, %d 3a (E/Z)/4a/1a
1
2
3
4
5
6
7
8
9
0
1.3
0
—
—
—
—
—
—
20/24
20/24
40/20
40/24
20/48
40/48
40/94
40/94
40/38
20/67
40/24
Trace/trace/>98
Trace/trace/>98
Complex mixture
Complex mixture
47 (91:9)/2/51
76 (99:1)/19/5
66 (83:17)/30/4
72 (88:12)/26/2
86 (95:5)/10/4
86 (95:5)/9/5
1.0
0.2
1.0
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.2
0.5
1.3
1.3
1.3
1.3
1.3
1.3
1.3
DMAe 2.6
NMPf 2.6
Pyridine 2.6
Et3N 2.6
Et3N 2.6
10
11
97 (99:1)/2/1
a
b
c
d
e
f
Compound 1a (1.0 mmol), Ti(O-i-Pr)4 (0–1.3 mmol), Me3SiCl (0–1.3 mmol), additive (0 or 2.6 mmol), and Mg powder (2.0 mmol) in THF (5 mL).
Equivalent of Ti(O-i-Pr)4.
Equivalent of Me3SiCl.
Determined by 1H NMR analysis of the crude mixture using an internal standard.
N,N-Dimethylacetamide.
N-Methyl-2-pyrrolidinone.
Table 2a
Run
Substrate 1
h
Products, %b 3 (E/Z)/4/1
Isolated yield of 3, %c
1
2
3
4
5
6
7
8
1a: Ar = 4-MeOC6H4
1b: Ar = Ph
1c: Ar = 4-ClC6H4
1d: Ar = 4-MeC6H4
1e: Ar = 3,4-(MeO)2C6H3
1f: Ar = 2-MeOC6H4
1g: Ar = 2,4,6-Me3C6H2
1h: Ar = 2-thienyl
24
48
72
48
48
72
24
72
97 (99:1)/2/1
95
77
58
85
65
51
76
53
95 (87:13)/5/0
75 (61:39)/17/8
93 (99:1)/6/1
89 (94:6)/9/2
66 (91:9)/15/19
97 (90:10)/3/0
61 (10:90)/17/22
1i: Ar =
9
48
24
60 (65:35)/16/24
95 (47:53)/0/5
49
88
10d
Acetophenone
a
Compound 1 (1.0 mmol), Ti(O-i-Pr)4 (1.3 mmol), Me3SiCl (1.3 mmol), Et3N (2.6 mmol), and Mg powder (2.0 mmol) in THF (5 mL) at 40 °C.
Determined by 1H NMR analysis of the crude mixture using an internal standard.
As a mixture of E and Z isomers of 3 after column chromatography.
b
c
d
The reaction was performed with 1 equiv of Ti(O-i-Pr)4 and 2 equiv of Me3SiCl in the absence of Et3N.

S. Okamoto et al. / Tetrahedron Letters 51 (2010) 387–390
389
and showed low selectivity. Interestingly, the reaction of 2-thio-
phenecarboxaldehyde (1h) gave (Z)-3h predominantly, presum-
ably due to an effect of coordination of the sulfur atom to the
active titanium species (run 8). The reaction of acetophenone with
the LVT reagent also proceeded smoothly in the absence of Et3N to
provide 2,3-diphenyl-2-butene in good yield, albeit with low E/Z
selectivity (run 10). The reaction of aliphatic aldehydes gave a
complex mixture involving the corresponding primary alcohol
generated by simple reduction (data not shown). As a result, the re-
agent could reductively couple aryl aldehydes and ketones (with-
out Et3N) at 40 °C by a simple mixing of the reagents and
substrate to provide 1,2-diarylethylene derivatives, although
somewhat narrow scope on the substrate substitution was
observed.
Figure 1. UV–vis absorption spectra of polymer 5j: In CH2Cl2 (10ꢀ2 mg/mL).
Periasamy and co-workers have reported TiCl4/Et3N reagent for
reductive coupling of aromatic aldehydes to the corresponding
diols, where Et3N reduces TiCl4 and is converted to the correspond-
ing iminium salt.6 To confirm this possibility in the present reac-
tion, we carried out the reaction of 1a with Ti(O-i-Pr)4/Me3SiCl/
Mg in the presence of less-volatile n-Bu3N instead of Et3N. The
NMR analysis of the crude mixture confirmed the production of
3a (95% NMR yield, E/Z = 55:45) with less than 5% of diols 4a and
quantitative recovery of n-Bu3N. The result indicates that an added
amine did not reduce titanium compound(s) but it might act as a
Lewis base to coordinate to the Ti atom in an active species. Since
the addition of 1 equiv of Et3N was found to be inefficient, it can be
assumed that the active titanium species stabilized by coordina-
tion with two molecules of Et3N may present as a monomeric form
and is suitable for deoxygenation of the titanium pinacolate inter-
mediates. However, the exact role of Et3N effecting on minimizing
production of diols is unclear at this time and its explanation must
await further study.
The reaction conditions for the McMurry-type coupling were
preliminarily applied to the polymerization reaction starting from
aryl dialdehydes 1j and 1k (Scheme 2).7 Thus, a mixture of 1j8 and
1k9 with Ti(O-i-Pr)4 (2.6 equiv), Me3SiCl (2.6 equiv), Et3N
(5.2 equiv), and Mg powder (4 equiv) in THF was stirred for 48 h
at 50 °C to produce polymers 5j (Mn = 4.74 ꢁ 103, Mw/Mn = 2.50,
51% yield) and 5k (Mn = 6.94 ꢁ 103, Mw/Mn = 2.15, 65% yield),
respectively.
Figure 1 shows UV–vis absorption spectra of polymer 5j. In the
region of longer wavelength, the maximum absorption (kmax abs) of
5j thus obtained was observed at 434 nm. Whereas the polymer 5j
(Mn = 3.57 ꢁ 103, Mw/Mn = 2.09) prepared in the absence of Et3N
has its kmax abs at 373 nm. The polymer 5j produced by the reaction
Figure 2. 1H NMR spectra of polymer 5j (CDCl3, 500 MHz).
derived from the reaction without Et3N. It can be explained by
assuming that conjugation of main chain in polymer 5j may be bro-
ken by 1,2-diol structures and the presence of Et3N could minimize
the formation of 1,2-diol. By comparison with UV–vis data of olig-
omers of type 5j reported in the literature,10 it was estimated that
the polymer 5j generated in the presence of Et3N involved an ex-
tended conjugation length of 4–6 phenylene–vinylene units. The
1H NMR spectra of polymer 5j indicated aromatic and olefinic pro-
tons of conjugated chain as well as small peaks for diol (and/or its
silyl ether) structure around 4.6 ppm (Fig. 2). Similar results were
in the presence of Et3N had more extended p-conjugation than that
obtained in the case of polymer 5k (fluorescence: kmax
at
em
456 nm excited at 385 nm), the conjugation-extending length of
which was estimated to be 4–6 arylene–vinylene units by compar-
ison of its UV-absorption and fluorescence data with those of the
oligomers of type 5k reported.11
In addition to the McMurry-type coupling, we found that a Ti(O-
i-Pr)4/Me3SiCl/Mg reagent couples aldimines to the corresponding
1,2-diamines.5 As revealed from Table 3, in which representative
results are shown, aromatic as well as aliphatic aldimines12 were
reacted with the reagent to give 1,2-diamines dl-selectively,
although the yields were not necessarily high. In these reactions,
the major side-reaction was reduction of 2 providing the corre-
sponding secondary amines (RCH2NHR0). Study for improvement
of the reaction is underway.
In summary, we have demonstrated that a new low valent tita-
nium reagent, Ti(O-i-Pr)4/Me3SiCl/Mg, enables McMurry coupling
of aryl aldehydes to biaryl olefins to be carried out under mild reac-
Scheme 2. Polymerization of dialdehydes.

390
S. Okamoto et al. / Tetrahedron Letters 51 (2010) 387–390
(h) Sato, F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000, 100, 2835; (i) Kulinkovich,
Table 3
Reactions of aldimines 2a
O. G.; de Meijere, A. Chem. Rev. 2000, 100, 2789; (j) Eisch, J. J. J. Organomet.
Chem. 2001, 617–618, 148; (k) Sato, F.; Okamoto, S. Adv. Synth. Catal. 2001, 343,
759; (l) Sato, F.; Urabe, H. In Titanium and Zirconium in Organic Synthesis; Marek,
I., Ed.; Wiley-VCH: Weinheim, Germany, 2002; pp 319–354.
2. Rele, A. M.; Nayak, S. K.; Chattopadhyay, S. Tetrahedron 2008, 64, 7225. and
references cited therein.
3. Ohkubo, M.; Mochizuki, S.; Sano, T.; Kawaguchi, Y.; Okamoto, S. Org. Lett. 2007,
9, 773.
4. For pinacol coupling, see: Lipski, T. A.; Hilfiker, M. A.; Nelson, S. G. J. Org. Chem.
1997, 62, 4566. and references cited therein.
5. Review for imino pinacol coupling: Lucet, D.; Le Gall, T.; Mioskowski, C. Angew.
Chem., Int. Ed. 1998, 37, 2580.
Run
Substrate 2
Product 6
Isolated yield, %
R
R’
dl:mesob
6. Periasamy, M.; Srinivas, G.; Karunakar, G. V.; Bharathi, P. Tetrahedron Lett. 1999,
40, 7577.
7. Cooke, A. W.; Wagener, K. B. Macromolecules 1991, 24, 1404.
8. Demir, A. S.; Reis, Ö. Tetrahedron 2004, 60, 3803.
9. Anuragudom, P.; Newaz, S. S.; Phanichphant, S.; Lee, T. R. Macromolecules 2006,
39, 3494.
10. Jiu, T.; Li, Y.; Liu, X.; Liu, H.; Li, C.; Ye, J.; Zhu, D. J. Polym. Sci., Part A: Polym.
Chem. 2007, 45, 911.
11. Liu, Q.; Liu, W.; Yao, B.; Tian, H.; Xie, Z.; Geng, Y.; Wang, F. Macromolecules
2007, 40, 1851.
12. Faugeroux, V.; Génisson, Y.; Salma, Y.; Constant, P.; Baltas, M. Bioorg. Med.
Chem. 2007, 15, 5866. and references cited therein.
1
2
3
4
5
6
7
8
9
n-Bu
i-Bu
i-Pr
cycl-Hex
t-Bu
Ph
Ph
2-Furyl
2-Thienyl
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
Ph
88:12
88:12
91:9
>99:1
No reaction
92:8
76:23
61:39
82:18
18
23
32
15
74
66
53
40
PhCH2
PhCH2
a
Compound 2 (1.0 mmol), Ti(O-i-Pr)4 (1.0 mmol), Me3SiCl (2.0 mmol), and Mg
13. General procedure for carbonyl coupling with Ti(O-i-Pr)4/Me3SiCl/Mg/Et3N
powder (4.0 mmol) in THF (10 mL).
Determined by 1H NMR analysis of the crude mixture.
b
reagent: To
a mixture of aldehyde 1 (1.00 mmol), Ti(O-i-Pr)4 (0.386 mL,
1.30 mmol), Et3N (0.360 mL, 2.60 mmol), and Mg powder (49 mg, 2.0 mmol)
in THF (5 mL) was added Me3SiCl (0.165 mL, 1.30 mmol) at 40 °C. The mixture
was stirred for 24–72 h at this temperature and then quenched by the addition
of aqueous 1 M HCl. The resulting mixture was extracted with AcOEt. The
combined organic layers were dried over MgSO4, filtrated through a pad of
Celite, and concentrated. The residue was purified by column chromatography
on silica gel (hexane/AcOEt) to give 1,2-diarylethylene 3. Procedure for
tion conditions with simple operation,13 where the addition of
Et3N was effective in minimizing the formation of the correspond-
ing 1,2-diols. The reagent also coupled aldimines to 1,2-diamines.
Further investigation for improving efficiency of the methods, con-
firming a role of an additive (Et3N), and their synthetic application
is underway in our laboratory.
polymerization with Ti(O-i-Pr)4/Me3SiCl/Mg/Et3N reagent: To
a mixture of
dialdehyde 1j or 1k (0.50 mmol), Ti(O-i-Pr)4 (0.385 mL, 1.30 mmol), Et3N
(0.36 mL, 2.60 mmol), and Mg powder (49 mg, 2.0 mmol) in THF (5.0 mL) was
added Me3SiCl (0.165 mL, 1.30 mmol) at 50 °C. The mixture was stirred for 24–
96 h at this temperature and then quenched by the addition of aqueous 1 M
HCl. The resulting mixture was extracted with CHCl3. The combined organic
layers were washed with water, concentrated, and dried in vacuo. The residue
was twice reprecipitated from chloroform/methanol or THF/methanol and
then dried in vacuo to give 2j or 2k. General procedure for imino-pinacol coupling
with Ti(O-i-Pr)4/Me3SiCl/Mg reagent: To a mixture of imine 2 (1.00 mmol), Ti(O-
i-Pr)4 (0.297 mL, 1.00 mmol), and Mg powder (98 mg, 4.0 mmol) in THF
(10 mL) was added Me3SiCl (0.254 mL, 2.00 mmol) at room temperature. The
mixture was stirred for 20–24 h at this temperature and then quenched by the
addition of aqueous 1 M NaOH (ꢂ0.5 mL). After addition of NaF (ꢂ1 g) and
Celite (ꢂ1 g), the resulting mixture was stirred for 1 h and then filtrated
through a pad of Celite. The filtrate was concentrated to dryness and the
residue was purified by column chromatography on silica gel (hexane/AcOEt)
to give 1,2-diarylethylene-1,2-diamine 6.
Acknowledgment
We thank the Ministry of Education, Culture, Sports, Science,
and Technology (Japan) for financial support.
References and notes
1. (a) McMurry, J. E.; Fleming, M. P. J. Am. Chem. Soc. 1974, 96, 4708; (b)
Mukaiyama, T.; Sato, T.; Hanna, J. Chem. Lett. 1973, 1041; (c) McMurry, J. E.
Chem. Rev. 1989, 89, 1513; (d) Lenoir, D. Synthesis 1989, 883; (e) Kahn, B. E.;
Rieke, R. D. Chem. Rev. 1988, 88, 733; (f) Fürstner, A.; Bogdanovic, B. Angew.
Chem., Int. Ed. 1996, 35, 2442; (g) Ephritikhine, M. Chem. Commun. 1998, 2549;