Communications
upon isolation. Similarly, transfer of nPr was successful from
of amines where the potential for oxidation to the imine
exists. A range of benzylamines was alkylated successfully
with remarkably high product yields (Table 3). The formation
of alkylated amines using this approach represents an
alternative to the more established Buchwald–Hartwig ami-
nation chemistry.[12]
di-n-propylamine (Table 1, entry 3), but was improved by
using tri-n-propylamine (Table 1, entry 4). The transfer of an
isopropyl group was found to be favorable, presumably
because of the formation of a ketimine intermediate. Iso-
propylamine was effective (Table 1, entry 5), but diisopropyl-
amine (Table 1, entry 6) gave complete conversion and an
excellent yield of the N-isopropyl product 4. Notably, after
five hours the reaction was essentially complete (Table 1,
entry 7), but the use of toluene as a solvent used a lower
reaction temperature, thereby leading to a lower conversion
of substrate into product. The use of [{Cp*IrCl2}2] as a catalyst
(Table 1, entry 9) was significantly less effective than the
corresponding iodide catalyst. When amine donors containing
both ethyl and isopropyl groups were used (Table 1, entries 9
and 10), both groups were transferred but N-isopropylaniline
(4) was the major product. Cyclohexylamine (Table 1,
entry 12) was also successfully used as an alkylating agent,
leading to N-alkylated product 5 in very good yield. In all
cases, no over-alkylation to give the tertiary amine was
detected.
Table 3: Conversion of benzylamines into N-isopropyl derivatives.
Entry
Benzylamine substrate
Yield [%][a]
1
2
3
4
5
6
7
8
9
PhCH2NH2
97
99
98
98
99
98
98
98
98
p-MeC6H4CH2NH2
p-MeOC6H4CH2NH2
p-ClC6H4CH2NH2
p-F3CC6H4CH2NH2
3,4-(OCH2O)C6H3CH2NH2
3,4-(MeO)2C6H3CH2NH2
PhCH(Me)NH2
Ph2CHNH2
[a] Reaction conditions: aniline (1 mmol), (iPr)2NH (3 mmol),
[{Cp*IrI2]2] (1 mol%), xylene (2 mL), 1558C, 10 h. Yield of isolated
product after column chromatography is based on aniline.
We then investigated the transfer of the isopropyl group
from diisopropylamine to a range of anilines, as identified in
Table 2. In the majority of cases, the N-isopropylaniline was
isolated in excellent yield. Even the electron-deficient 4-
When the reaction shown in entry 8 of Table 3 was
repeated in the presence of (S)-binap (4 mol%; binap = 2,2’-
bis(diphenylphosphanyl)-1,1ꢀ-binaphthyl), the product was
formed with 6% ee. This result is consistent with the known
ability of [Cp*IrI2] to racemize amines.[11]
Table 2: Conversion of anilines into N-isopropylanilines.
In all of the reactions identified in Table 3, the N-
isopropyl-N-benzylamine product was obtained without any
contamination from tertiary amines or dibenzylamines. The
lack of formation of any dibenzylamine was particularly
noteworthy, since oxidation of benzylamine into an imine
would be expected to occur under these conditions. Indeed, a
control reaction demonstrated that in the absence of diiso-
propylamine, benzylamine (6) underwent a self-coupling
reaction to afford dibenzylamine (7). However, we also
discovered that under the same reaction conditions, the
reaction of dibenzylamine (7) with diisopropylamine led to
the formation of N-isopropyl-N-benzylamine (8) in a reason-
able yield (Scheme 2). This implies that if any dibenzylamine
is formed in the reaction of benzylamine with diisopropyl-
amine, then the reaction is self-correcting and leads to the
observed N-isopropyl derivatives.
Entry
Aniline substrate
Yield [%][a]
1
2
3
4
5
6
7
8
PhNH2
98
99
99
99
99
97
95
52
26
99
97
83
99
4-MeC6H4NH2
4-(tBu)C6H4NH2
4-MeOC6H4NH2
3,4-(OCH2O)C6H3NH2
4-(MeO2C)C6H4NH2
4-FC6H4NH2
3-F3CC6H4NH2
4-O2NC6H4NH2
3-MeC6H4NH2
3-ClC6H4NH2
9
10
11
12
13
2-MeC6H4NH2
5-aminoindane
[a] Reaction conditions: aniline (1 mmol), (iPr)2NH (3 mmol),
[{Cp*IrI2]2] (1 mol%), xylene (2 mL), 1558C, 10 h. Yield of isolated
product after column chromatography is based on aniline.
When dibenzylamine (7) was reacted under the same
conditions with diethylamine or triethylamine, the mixed
secondary amine, N-benzyl-N-ethylamine was formed but
methoxycarbonyl- and 4-fluoroaniline (Table 2, entries 6 and
7) were successfully alkylated; for the 3-trifluoromethyl- and
4-nitroanilines (Table 2, entries 8 and 9) the low yields of the
isolated products were a consequence of incomplete con-
version under these reaction conditions. The reaction of the
ortho-substituted aniline (Table 2, entry 12) also led to a
lower yield of isolated product.
In the case of aniline alkylation, it is only the diisopropyl-
amine which is able to undergo oxidation to the imine, and
hence selectivity for the mixed product is expected to be
favored. We therefore turned our attention to the alkylation
Scheme 2. Self-coupling of benzylamine and alkyl exchange of diben-
zylamine.
7376
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 7375 –7378