Reductive self-coupling reaction of imines and aldehydes induced by strontium metal

Article abstract of DOI:10.1246/cl.2009.984

Aromatic aldimines reacted with Sr in the presence of a catalytic amount of iodine to give self-coupling products in good yields, whereas aromatic and aliphatic aldehydes underwent a similar reaction effected by the combined use of Sr and Al(OEt)₃. Copyright

Full text of DOI:10.1246/cl.2009.984

984
Chemistry Letters Vol.38, No.10 (2009)
Reductive Self-coupling Reaction of Imines and Aldehydes Induced by Strontium Metal
Norikazu Miyoshi,ꢀ1 Tadashi Kohno,1 Makoto Wada,1 Sei Matsunaga,2
Isao Mizota,2 and Makoto Shimizuꢀ2
1Department of Chemistry, Faculty of Integrated Arts and Sciences, The University of Tokushima,
1-1 Minamijosanjima, Tokushima 770-8502
2Department of Chemistry for Materials, Graduate School of Engineering, Mie University, Tsu 514-8507
(Received July 30, 2009; CL-090714; E-mail: miyoshi@ias.tokushima-u.ac.jp, mshimizu@chem.mie-u.ac.jp)
Aromatic aldimines reacted with Sr in the presence of a cat-
Table 2. Self-coupling reaction of various imines 1a
alytic amount of iodine to give self-coupling products in good
yields, whereas aromatic and aliphatic aldehydes underwent
a similar reaction effected by the combined use of Sr and
Al(OEt)3.
R
R
NH
N
Sr, cat. I2
Ar
Ar
Ar
THF, 2.5 h
2
1
HN
R
Entry
Ar
R
Yield/%b
Dl:mesoc
Synthetic reactions using strontium compounds are recently
of increasing interest. Although few studies of the preparation
and reactivity of organostrontium compounds were found in
the literature1 a decade ago, we have reported the alkylation of
aldehydes with alkyl iodides using metallic strontium.2 Among
other intriguing results, we found that alkylation of imines with
alkyl iodides using strontium metal gave the adducts in good
yields.3 Compounds incorporating 1,2-diamine, 1,2-hydroxy-
amine, and 1,2-diol are currently the topics of studies, and their
intriguing behaviors offer wide extensions of these particular
fields.4 Although the reductive coupling of imines or aldehydes
seems to be a straightforward way to prepare such compounds,
methods under milder conditions for imines5 appear to be still
needed as compared with their carbonyl counterparts.6 Herein
we wish to report the reductive self-coupling reaction of imines
or aldehydes using metallic strontium as a one-electron transfer
agent in the presence of a catalytic amount of iodine and/or alu-
minum triethoxide.
1
2
3
4
5
6
7
8
9
Ph
4-MeOC6H4
Ph
4-MeOC6H4
Ph
4-MeC6H4
4-ClC6H4
94
97
88
79
36
51
95
63:37d
69:31e
67:33d
46:54d
57:43e
50:50f
50:50g
Ph
4-ClC6H4
4-NCC6H4
2-Naphthyl
1-Naphthyl
Ph(C=NPh)Meh
Ph
Ph
Ph
Ph
Ph
trace Not determined
33i 14:86d
aCarried out according to a typical procedure (Ref. 7). bIsolated
yield. cRatio determined by 1H NMR. dFor structure determina-
e
f
tion, see Ref. 5c. Structure determination (Ref. 5b). Structure
determination (Ref. 5d). gStructure determination (Ref. 5e).
hKetimine derived from acetophenone and aniline was used.
iN-Phenyl-1-phenylethylamine was also obtained in 16% yield.
(Entries 4 and 5), but a decreased yield was observed in MeOH
(Entry 6). The reactions did not take place in CH2Cl2, Et2O, and
MeCN (Entries 1–3). Under the optimized conditions a variety
of imines were subjected to the imino pinacol coupling, and
the results are summarized in Table 2.
When N-benzylideneaniline (1a) was treated with strontium
metal, the desired coupling product 2a was obtained in very low
yields, whereas the addition of a catalytic amount of iodine im-
proved the product yield (Table 1). This may be due to the acti-
vation effect of the metal surface as well as the ability as a Lewis
acid of the resulting strontium iodide. Regarding the solvent, the
reaction gave the diamine in good yields in DMF and THF
Using aldimines prepared from aromatic aldehydes and aro-
matic amines, the reactions afforded the corresponding self-cou-
pling products in good yields (Entries 1–4 and 7). Aldimines
having an electron-withdrawing group on the aromatic ring such
as chloro or nitrile slightly decreased the product yields (Entries
5 and 6). However, dimerization of imines having a nitrophenyl
group and the N-alkyl aldimine prepared from benzaldehyde and
benzylamine did not occur. Even in the case of an intramolecular
coupling of aldimine such as N,N0-dibenzylideneethylene-1,2-
diamine, the desired product was not formed. These results indi-
cate that the reaction is effective for aromatic aldimines, and that
the electron deficiency of the imines affects the reactivities. 2-
Naphthylmethylideneaniline gave the coupling product in 95%
yield, while 1-naphthylmethylideneaniline did not (Entries 7
and 8). Using a ketimine from acetophenone and aniline, the
coupling product was formed in 33% yield, indicating that the
reaction was sensitive to steric congestion (Entry 9).
Table 1. Investigation into the solventsa
Ph
Ph
NH
Sr, cat. I2
THF, 2 h
N
Ph
Ph
2a
Ph
1a
HN
Ph
Entry
Solvent
Yield/%b
1
2
3
4
5
6
CH2Cl2
Et2O
MeCN
DMF
THF
No reaction
No reaction
No reaction
63
88c
MeOH
15
There are significant differences between imines and car-
bonyl counterparts in reductive self-coupling reactions.6 In fact,
pinacol coupling reaction of benzaldehyde did not take place but
a simple reduction product, benzyl alcohol, was obtained in 90%
aCarried out according to a typical procedure (Ref. 7).
bIsolated yield. cDl:meso = 75:25. The structures were de-
termined by comparison with reported data (Ref. 5b).
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.10 (2009)
985
Table 3. Pinacol coupling of aldehydes 3 under various con-
ditionsa
served between imine and carbonyl moieties may make the pres-
ent procedure a useful addition to the existing methodologies.
OH
Sr, cat. I2
O
Additive (0.5 equiv)
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas ‘‘Advanced Molecular Trans-forma-
tions of Carbon Resources’’ from MEXT.
R
R
R
THF
OH
4
3
Entry
R
Additive Temp/ꢂC Yield/%b Dl:mesoc
References and Notes
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
none
rt
0
0
11
0
37
0
41
18
63
26
61
23
57
87
53
—
—
91:9
—
67:33
—
67:33
67:33
75:25
67:33
60:40
91:9
73:27
62:38
76:24
1
a) N. A. Bell, W. E. Lindsell, in Comprehensive Organo-
metallic Chemistry, ed. by G. Wilkinson, F. G. A. Stone,
E. W. Abel, Pergamon, Oxford, 1982, Vol. 1. b) W. E.
Lindsell, in Comprehensive Organometallic Chemistry II,
ed. by E. W. Abel, F. G. A. Stone, G. Wilkinson, Pergamon,
Oxford, 1995, Vol. 1. c) N. Miyoshi, in Houben-Weyl: Sci-
ence of Synthesis, ed. by H. Yamamoto, Thieme, Stuttgart,
2004, Vol. 7, p. 685, and earlier references therein.
N. Miyoshi, K. Kamiura, H. Oka, A. Kita, R. Kuwata, D.
Ikehara, M. Wada, Bull. Chem. Soc. Jpn. 2004, 77, 341.
N. Miyoshi, D. Ikehara, T. Kohno, A. Matsui, M. Wada,
Chem. Lett. 2005, 34, 760.
TMSOTfd 0 to rt
TBSOTfd 0 to rt
TfOHd
AlEt3
Al(OPh)3 0 to rt
Al(OiPr)3 0 to rt
Al(OiPr)3
Al(OEt)3
0 to rt
0 to rt
d
0 to rt
0 to rt
2
3
4
10
11
Al(OEt)3 ꢃ78 to rt
4-ClC6H4 Al(OEt)3
0 to rt
0 to rt
0 to rt
0 to rt
0 to rt
12 4-MeOC6H4 Al(OEt)3
13 4-MeC6H4 Al(OEt)3
a) D. Lucet, T. Le Gall, C. Mioskowski, Angew. Chem., Int.
Ed. 1998, 37, 2580. b) For an unprecedented cleavage of
1,2-diamines, see: M. Shimizu, H. Makino, Tetrahedron
Lett. 2001, 42, 8865.
14
Cy
15 PhCH2CH2 Al(OEt)3
Al(OEt)3
aCarried out according to a typical procedure (Ref. 7), except for
the use of an additive. bIsolated yield. cRatio determined by
1H NMR and/or GLC. For structure determination, see Ref. 6b.
dAdditive (1.0 equiv) was used.
5
a) For a recent review on imino pinacol coupling covering
literatures from 1960 to 2006, see: V. Faugeroux, Y.
Genisson, Curr. Org. Chem. 2008, 12, 751. b) J. G. Smith,
I. Ho, J. Org. Chem. 1972, 37, 653. c) S. Ohtaka, K. Mori,
S. Uemura, Heteroat. Chem. 2001, 12, 309. d) J. G. Smith,
I. Ho, J. Org. Chem. 1973, 38, 2776. e) J. J. Eisch, P. O.
Fregene, Eur. J. Org. Chem. 2008, 4482. f) Enantioselec-
tive imino pinacol coupling, see: M. Shimizu, T. Iida, T.
Fujisawa, Chem. Lett. 1995, 609. g) Crossed imino pinacol
coupling of two different imines, see: M. Shimizu, I.
Suzuki, H. Makino, Synlett 2003, 1635.
yield under the present conditions (1.3 mmol Sr, cat I2, THF, rt,
1.5 h). In an effort to find conditions for the pinacol coupling re-
action of aldehydes, use of a series of additives was next exam-
ined. Table 3 summarizes the results.
As can be seen from Table 3, use of TBSOTf effected the
desired coupling (Entry 3), whereas much better results were ob-
tained with aluminum-containing Lewis acids. Among the alu-
minum compounds, aluminum triethoxide was found to be the
most effective to promote the pinacol coupling (Entries 5–10).
A branched aliphatic aldehyde serves as a good substrate for
the present pinacol coupling (Entry 14).
Useful chemoselectivity was observed. Treatment of a 1:1
mixture of the imine 1b and the aldehyde 3b with Sr in the pres-
ence of I2 and Al(OEt)3 gave selectively the imino pinacol prod-
uct 2b in good yield without formation of the pinacol arising
from the aldehyde 3b which was reduced to the alcohol 5
(Scheme 1).
In summary, the reductive self-coupling reaction of aromat-
ic imines with strontium metal gave 1,2-diamines in good yields,
while pinacol coupling of aldehydes was successful with the
combined use of strontium metal and aluminum triethoxide. Al-
though there is much room for the improvement of diastereose-
lectivity, this study has opened a possible use of strontium metal
as a useful one-electron transfer agent for imine and carbonyl
functionalities. Furthermore, the good chemoselectivity ob-
6
a) G. M. Robertson, in Comprehensive Organic Synthesis,
ed. by B. M. Trost, I. Fleming, Pergamon, Oxford, 1991,
Vol. 3, p. 563, and references therein. b) T. Mukaiyama,
N. Yoshimura, K. Igarashi, A. Kagayama, Tetrahedron
2001, 57, 2499. c) R. Hayakawa, M. Shimizu, Chem. Lett.
2000, 724. d) M. Shimizu, H. Goto, R. Hayakawa, Org.
Lett. 2002, 4, 4097. e) M. Shimizu, H. Okimura, N.
Manabe, I. Hachiya, Chem. Lett. 2008, 37, 28. f) For
crossed pinacol coupling between aldehydes and imines,
see: M. Shimizu, A. Iwata, H. Makino, Synlett 2002, 1538.
A typical procedure for the reductive self-coupling of imine
is as follows: Under an argon atmosphere, N-benzylidene-
aniline (182 mg, 1.00 mmol) and I2 (ca. 10 mg, 0.08 mmol)
were added successively to a THF (3 mL) suspension of Sr
(116 mg, 1.32 mmol) at rt. After stirring for 2 h, the reaction
mixture was quenched with 1 M HCl(aq) (3 mL), and the
whole reaction mixture was made basic to litmus with 5%
aq Na2CO3, filtered through a cake of celite. The organic
materials were extracted with Et2O (30 mL ꢁ 3), and the
combined organic layers were washed successively with
5% aq NaHSO3 and brine, and dried over anhydrous
Na2SO4. After evaporation of the solvent, the residue was
purified by column chromatography on Al2O3 (hexane:eth-
yl acetate = 10:1) to give 1,2-dianilino-1,2-diphenylethane
(162 mg, 88% yield, dl:meso = 75:25)5b and N-benzylani-
line (10 mg, 5% yield).
7
PMP
Sr (2.0 mmol)
Al (OEt)3 (0.5 mmol)
cat. I2
NH
PMP
O
N
Ph
Ph
2b
4-ClC6H4
OH
+
+
4-ClC6H4
Ph
3b
1b
5
THF
0 oC to rt, 12 h
HN
PMP
95% dl:meso= 82:18
(1.0 mmol)
(1.0 mmol)
76%
Scheme 1.
Published on the web (Advance View) September 12, 2009; doi:10.1246/cl.2009.984