Lewis base-catalyzed strecker-type reaction between trimethylsilyl cyanide and N-tosylimines in water-containing DMF

Article abstract of DOI:10.1246/cl.2005.318

Lewis base-catalyzed Strecker-type reaction between trimethylsilyl cyanide and N-tosylimines proceeded smoothly in dry DMF or water-containing DMF and the corresponding α-amino compounds were obtained in good to high yields. Copyright

Full text of DOI:10.1246/cl.2005.318

318
Chemistry Letters Vol.34, No.3 (2005)
Lewis Base-catalyzed Strecker-type Reaction between Trimethylsilyl Cyanide
and N-Tosylimines in Water-containing DMF
Eiki Takahashi,y;yy Hidehiko Fujisawa,y;yy Toshiharu Yanai,y;yy and Teruaki Mukaiyamaꢀy;yy
yCenter for Basic Research, The Kitasato Institute (TCI), 6-15-5 Toshima, Kita-ku, Tokyo 114-0003
yyKitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
(Received December 2, 2004; CL-041470)
Lewis base-catalyzed Strecker-type reaction between trime-
Lewis base catalyst, Strecker-type reaction between TMSCN
and N-tosylimines was considered. In this communication, we
would like to report on efficient Strecker-type reactions using
a catalytic amount of AcOLi in dry or water-containing DMF.
In the first place, reactions between N-tosylaldimine 1 and
TMSCN were tried in the presence of a catalytic amount of AcO-
Li in DMF at ꢁ45 ꢂC (Table 1). Then, the reactions were found
to proceed smoothly to afford the corresponding ꢀ-amino ni-
triles 2 in high yields (Entries 4 and 5).5 In these reactions, var-
ious counter cations of carboxylate anion such as sodium, potas-
sium, and ammonium turned out to be effective. When the reac-
tion was carried out in the presence of AcOLi in THF, 2 was ob-
tained only in 20% yield (Entry 3). On the other hand, the adduct
2 was afforded in a high yield in various solvents such as
CH2Cl2, toluene, and THF when ammonium carboxylates such
as AcONMe4 or PhCO2Nn-Bu4 were used (Entries 11, 13–15).
Next, AcOLi-catalyzed Strecker-type reaction was exam-
ined by using various N-tosylimines and TMSCN in the presence
of 10 mol % of AcOLi in DMF at ꢁ45 ꢂC (Table 2). Reactions of
aromatic aldimines that have an electron-withdrawing or -donat-
ing group proceeded smoothly and afforded the corresponding
ꢀ-amino nitriles in good to high yields (Entries 1–6). When an
aromatic aldimine containing another basic part such as dime-
thylamino-function was used, the corresponding ꢀ-amino nitrile
was also obtained in high yields (Entry 7). The cases were the
same when aliphatic aldimine and ketimine were used and the
desired products were obtained in high yields (Entries 8 and 9).
Then, Lewis base-catalyzed Strecker-type reaction was tried
in a water-containing solvent by using the above Lewis base cat-
alysts which were stable in water (Table 3). When the reaction
between aldimine 1 and TMSCN was carried out by using
thylsilyl cyanide and N-tosylimines proceeded smoothly in dry
DMF or water-containing DMF and the corresponding ꢀ-amino
compounds were obtained in good to high yields.
Strecker-type reaction between trimethylsilyl cyanide
(TMSCN) and imines is one of the most important tools for
the construction of ꢀ-amino nitriles.1 This reaction is generally
performed through activation of the acceptor imines with Lewis
acid, for which various methods have been reported. It is known
that fluoride anion activates TMSCN, however, a stoichiometric
amount of fluoride anion is generally required.
It was reported in the previous communication that trime-
thylsilyl (TMS) enolates were activated with Lewis base cata-
lysts such as the nitrogen and oxygen containing-anions generat-
ed from amides, imides, or carboxylic acids, and they worked as
a promoter of aldol and Michael reactions.2,3 These Lewis bases
also worked as useful catalysts for Mannich-type reaction be-
tween N-tosylaldimines and TMS enolates because they are nei-
ther deactivated nor decomposed by a basic nitrogen contained
in an aldimine, a starting material, and an amine, a product.4
In order to show more examples of the synthetic utility of a
Table 1.
Ts
Ts
H
NH
CN
N
Cat. (10 mol %)
Solv., −45 °C, Time
H+
+
Me3SiCN
(1.2 equiv.)
Cat.
Ph
Ph
1
2
Entry
Solv.
Time/h
Yielda/%
1
2
—
—
DMF
THF
12
12
6
36
n.d.
Table 2.
Ts
Ts
R'
3
AcOLi
AcOLi
AcOLi
AcONa
AcOK
THF
20
NH
H+
N
AcOLi (10 mol %)
4
DMF
DMF
DMF
DMF
DMF
DMF
DMF
THF
6
97
Me3SiCN
+
R
R'
96b,c
quant.
quant.
98
CN
DMF, −45 °C, 6 h
(1.2 equiv.)
5
6
R
6
6
Entry
R
R0
Yielda/%
7
6
1
2
3
4
5
6
7
8
9
4-ClC6H4
4-BrC6H4
4-NCC6H4
4-MeC6H4
4-MeOC6H4
2-Naphthyl
4-Me2NC6H4
c-Hexyl
H
H
98
95 (90b)
73
8
Phthalimide-K
AcONn-Bu4
AcONMe4
6
9
6
quant.
quant.
98
H
10
11
12
13
14
15
6
H
quant.
quant.
87
quant. (95b)
quant. (95b)
quant.
AcONMe4
6
H
PhCO2Nn-Bu4
PhCO2Nn-Bu4
PhCO2Nn-Bu4
PhCO2Nn-Bu4
DMF
CH2Cl2
Toluene
THF
6
93
quant.
H
6
H
6
12
98
97d
H
Me
Ph
aYield was determined by 1H NMR analysis (270 MHz) using
1,1,2,2-tetrachloroethane as an internal standard. bCat.: 1 mol
aYield was determined by 1H NMR analysis (270 MHz) using
1,1,2,2-tetrachloroethane as an internal standard. bIsolated yield.
c
d
%. Isolated yield. Reaction temp.: ꢁ78 ꢂC.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.3 (2005)
319
Table 3.
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try, 15, 1513 (2004). m) V. Banphavichit, W. Mansawat,
and W. Bhanthumnavin, Tetrahedron, 60, 10559 (2004).
Aldol reaction: a) H. Fujisawa and T. Mukaiyama, Chem.
Lett., 2002, 182. b) H. Fujisawa and T. Mukaiyama, Chem.
Lett., 2002, 858. c) T. Mukaiyama, H. Fujisawa, and T.
Nakagawa, Helv. Chim. Acta, 85, 4518 (2002). d) T.
Nakagawa, H. Fujisawa, and T. Mukaiyama, Chem. Lett.,
32, 462 (2003). e) T. Nakagawa, H. Fujisawa, and T.
Mukaiyama, Chem. Lett., 32, 696 (2003). f) T. Nakagawa,
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Fujisawa, Chem. Lett., 33, 1410 (2004).
Mannich-type reaction: a) H. Fujisawa, E. Takahashi, T.
Nakagawa, and T. Mukaiyama, Chem. Lett., 32, 1036
(2003). b) E. Takahashi, H. Fujisawa, and T. Mukaiyama,
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34, 84 (2005).
Ts
Ts
R
H+
Cat. (10 mol %)
N
NH
CN
Me3SiCN
+
Solv.−H2O, −45 °C, 6 h
R
H
(1.2 equiv.)
Yieldb
/%
Entry
R
Cat.
Solv. Solv.:H2Oa
1
2
Ph
Ph
Ph
Ph
Ph
Ph
—
DMF
DMF
DMF
DMF
THF
50:1
50:1
10:1
5:1
n.d.
98
AcOLi
AcOLi
AcOLi
AcOLi
3
95
92
4
5
10:1
10:1
10:1
10:1
50:1
10:1
10:1
n.d.
84
6
PhCO2Nn-Bu4 THF
7
4-ClC6H4
4-MeOC6H4
4-Me2NC6H4
2-Naphthyl
C6H11
AcOLi
AcOLi
AcOLi
AcOLi
AcOLi
DMF
DMF
DMF
DMF
DMF
quant.
96
98
8
2
9
10
11
83
89
aVolume ratio. bYield was determined by 1H NMR analysis (270
MHz) using 1,1,2,2-tetrachloroethane as an internal standard.
10 mol % of AcOLi at ꢁ45 ꢂC, it proceeded smoothly to afford 2
in high yields (Entries 2–4) while no reaction took place in the
absence of a catalyst. Further, no reaction was observed in
water-containing THF too when AcOLi was used (Entry 5).
On the other hand, when ammonium salts such as PhCO2-
Nn-Bu4 were used instead of AcOLi, it proceeded smoothly
and afforded 2 in high yield (Entry 6). Next, reactions of various
N-tosylimines with TMSCN in water-containing DMF were
tried and these reactions proceeded smoothly by using AcOLi
(Entries 9–11), which afforded the corresponding ꢀ-amino
nitriles in high yields.
Thus, Lewis base-catalyzed Strecker-type reaction between
TMSCN and N-tosylimines in dry or water-containing DMF was
established. This method is quite practical and is applicable to
the synthesis of various ꢀ-amino nitriles since the reaction pro-
ceeded smoothly in the presence of a mild, readily available yet
inexpensive Lewis base catalyst in a not-strictly-anhydrous sol-
vent. Further development of this reaction is now in progress.
3
4
5
General experimental procedure is as follows: To a stirred
solution of AcOLi (0.02 mmol) in DMF (0.3 mL) were added
successively a solution of TMSCN (0.24 mmol) in DMF
(0.6 mL) and a solution of N-tosylimine (0.2 mmol) in
DMF (0.6 mL) at ꢁ45 ꢂC. After the mixture was further stir-
red for 6 h at the same temperature, it was quenched with sat-
urated aqueous NH4Cl. The mixture was extracted with
AcOEt. Organic layer was washed with brine and dried over
anhydrous Na2SO4. After filtration and evaporation of the
solvent, the crude product was purified by preparative TLC
to give the corresponding ꢀ-amino nitriles. Products and
yields were as reported in the text.
This study was supported in part by the Grant of the 21st
Century COE Program from Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan.
References and Notes
1
For recent reports relevant to Strecker-type reaction: a) I.
Ojima, S. Inaba, and K. Nakatsugawa, Chem. Lett., 1975,
331. b) F. A. Davis, R. E. Reddy, and P. S. Portonovo,
Tetrahedron Lett., 35, 9351 (1994). c) S. Kobayashi, H.
Ishitani, and M. Ueno, Synlett, 1997, 115. d) M. S. Sigman
Published on the web (Advance View) February 5, 2005; DOI 10.1246/cl.2005.318