Mendeleev Commun., 2002, 12(6), 230–231
Iminopinacol coupling with lithium: electron-transfer mediators
Electron A. Mistryukov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 095 135 5328
1
0.1070/MC2002v012n06ABEH001617
The addition of tert-butyl borate or ethyl formate to N-alkylbenzalimines directs the reaction pathway from the Birch reduction to
the pinacol-type coupling with lithium in THF; an analogous reaction with a dimethylimmonium salt requires a trace titanium
catalyst as the electron-transfer mediator.
The reductive coupling of aliphatic and aromatic imines is of
current interest, motivated by a promising perspective in direct-
i, solvent
ii, H
+
ing the stereochemistry of reaction. This interest is justified by
unique properties of vicinal diamines as bases and chiral
PhCHLi
PhCH
NLiR
NLiR
PhCH2NHR
4
2
5
1
ligands. The relevant publications considered a great variety of
reducing metals (Mg, Zn, Cr, Ti, Ni, Nb, Sm and Yb) and metal
Li/THF
mediator
combinations.2–9 Considering the mechanistic aspects of the
PhCH=NR
(1)
reductive coupling, we were intrigued by the conspicuous absence
1
of lithium which, to the best of our knowledge, was mentioned
a R = SiMe3
b R = Me
c R = Pr
d R = But
only once as a metal of no value for the iminopinacol coupling.10
PhCH(NHR)–CH(NHR)Ph
i
The aim of this study was to comprehend the observed specific
nature of lithium as a coupling metal, the effects of additives and
the nitrogen substitution. The results are presented in Table 1.†
3
Ph
Ph
Li/THF
+
–
PhCH=N Me Cl
Ti(OPri)4
HC CH
(2)
(3)
†
2
General procedure for iminopinacol coupling with lithium. All reac-
tions (except for runs 10 and 11, where a polypropylene stirrer was used)
were run in argon with a stainless steel overhead stirrer, lithium was
added as small chips cut from 0.2 mm foil. Ethyl formate was distilled
over lithium and stored under argon.
1e
Me N
NMe2
2
3
e
OEt
N(R)CH
1
,2-Diphenylethylene-1,2-diamine. One-pot procedure: to a mixture
of 0.1 mol Li and 0.1 mol (21 ml) of HMDS in 60 ml of THF was added
.05 mol (6.5 ml) of isopropenylbenzene at 25–32 °C. After dissolution
HCOOEt
PhCH
2
OLi
0
6
of the metal (~1 h), benzaldehyde (0.1 mol, 10.14 ml) was added. By
cooling, the temperature was kept below 25 °C. When the exothermic
formation of N-trimethylsilyl Schiff base 1a was completed, the second
portion of lithium (0.1 mol) was added, and the reaction mixture was
kept at ~5 °C (at higher temperatures, the decomposition of THF with
ethylene evolution became noticeable). After 1 h, the dissolution of the
metal was almost complete, and the reaction was treated with 40 ml of
conc. HCl in 30 ml of water after 2 h at room temperature. The crystal-
line solid was filtered off and washed with THF. The yield of chlorides is
OLi
Li/THF
1
HCOOEt
HC
2
3
(4)
(5)
OEt
N(R)B(OBu ) Li
B(OBut)3
t
3
2
PhCH
3
Li/THF
B(OBut)3
B (OBu ) Li
–
t
+
(6)
(7)
13.1 g (meso/rac, 30:70). This mixture, after aqueous NaOH–THF treat-
3
ment gave 9.4 g (88.7%) of a crystalline mixture of isomers, the crystal-
lization of which from hexane–THF gave 6.8 g of racemic diamine
Li/O=P(NMe2)3
THF
1e
PhCH NMe
2
2
1
2
(
64%), mp 72 °C. H NMR ([ H ]DMSO) d: 1.65 (br.s, 4H), 3.9 (s, 2H),
6
7
.1–7.3 (m, 10H). A diagnostic signal of the meso-isomer is 3.8 (s).
Coupling of N-alkyl Schiff bases in the presence of the mediator. A
Mediators
A = B(OBut)3
E = liquid NH
F = Bu C H –C H Bu
3
mixture of 1b (0.025 mol), ethyl formate (0.03 mol), 25 ml THF and Li
t
t
B = BF ·OEt
3
2
6 4 6 4
(
0.04 mol) was stirred with cooling (9–10 °C). In about 3 min, the Li chips
i
C = BF ·OEt /NEt
G = Ti(OPr )
4
3
2
3
became shiny and the solution became yellow. After 2 h cooling was
terminated, and the temperature was kept ambient for 1 h. Then, the
reaction mixture was treated with 15 ml of 6 N NaOH and, after pressure
D = HCOOEt
H = OP(NMe2)3
Scheme 1
filtration over silica, rotary evaporated. The mixture of isomers (yield,
1
Table 1 The iminopinacol coupling of benzalimines with lithium: the
yields of vicinal diamines in relation to the nitrogen substitution and the
type of electron-transfer mediators.
3
.0 g) was separated by crystallization from hexane. Solid isomer (meso),
1
2
H NMR ([ H ]DMSO) d: 2.05 (s, 6H), 3.62 (s, 2H), 7.15–7.3 (m, 10H).
6
1
Liquid isomer (rac), H NMR, d: 2.12 (s, 6H), 3.45 (s, 2H), 7.0–7.15
(
m, 10H). The reactions with mediators A, B and C were performed in a
meso + rac,
yield (%)
Reduction
(%)
similar way using ammonia for the decomposition.
Entry
Imine
Mediator
meso/rac
Coupling of immonium salt 1e (polypropylene stirrer). Salt 1e was
a
9
1
1a
1b
1b
1b
1b
1b
1c
1d
1a
1e
1e
A
B
C
D
E
F
D
D
2b, 91
2b, 80
2b, 85
2b, 90
2b, ca. 5
4:5
1:1
4:6
1:1
1:1
6
10
5
prepared from aminal according to a published procedure; the mixture
of benzaldehyde, liquid dimethylamine and calcium chloride was kept in
a pressure vessel for 12 h at room temperature. The mixture of 1e
(
a
2
a
3
4
5
6
7
8
9
5
0.52 mol), 50 ml of THF and Li (0.6 mol) was stirred for 5 min and
95
80
15
97
10
5
0
3
4
.14 ml of titanium isopropylate was added. The temperature was kept at
3–35 °C. After additional stirring for 2 h, the mixture was treated with
ml of water and then 5 ml of 12 N NaOH. The evaporation of the
2c, 70
1:2
organic fraction gave 5.2 g of a 1:1 mixture of racemic and meso
diamines 3e. By crystallization from hexane, the less soluble meso-
none
G
H
2a, 81
2e, 90
3:7
1:1
—
1
1
0b
1
1
isomer was isolated. H NMR (CDCl ) d: 2.0 (s, 12H), 4.17 (s, 2H),
7
phthalate. H NMR, d: 2.24 (s, 4H), 4.22 (s, 2H), 7.15–6.85 (m, 10H).
3
95
.25-7.45 (m, 10H). Racemic 3e was obtained by crystallization of 3e
1
a
b
After the hydrolysis of borates. One-pot procedure based on benzaldehyde.
–
230 –