Tetrahedron Letters
Titanium-mediated reductive cross-coupling reactions of imines
with nitriles: an efficient route for the synthesis of
or 1,2-diketones
a-aminoketones
Haoyi Chen a, Guoqin Fan a, Shi Li a, Kebin Mao b, Yuanhong Liu a,
⇑
a State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, People’s Republic
of China
b College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
The reaction of imines with low-valent titanium species, generated in situ by using Ti(OiPr)4/2 c-C5H9-
Article history:
Received 5 November 2013
Revised 13 January 2014
Accepted 20 January 2014
Available online 24 January 2014
MgCl reagent, affords titanium–imine complex, which can couple with nitriles to provide 2,5-diazatitana-
cyclopentenes.
a-Aminoketones are obtained in good yields by quenching the corresponding
2,5-diazatitanacyclopentenes with aqueous HCl solution. However, when the reaction is first quenched
with MeOH in air followed by addition of aqueous HCl solution, 1,2-diketones are formed in good to high
yields.
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
Titanium–imine complex
2,5-Diazatitanacyclopentene
Reductive cross-coupling
Nitrile
a-Aminoketone
1,2-Diketone
Titanium-mediated reductive cross-coupling reactions of unsat-
unsaturated molecule such as nitriles have far less been studied.
In 1992, Rothwell and co-workers reported that the reaction of
urated molecules such as alkynes, alkenes, nitriles, imines, ketones
etc. have received much attention during the last several
decades.1,2 The in situ generated titanacycles can display diverse
reactivities toward suitable electrophiles leading to a wide range
of selective transformations.2 Although much progress has been
achieved in this chemistry, most of the studies concentrated on
the metallacycles in which at least one of the components is alkyne
or alkene.1 There are few examples for the preparation of heterom-
etallacycles via coupling reactions of two heteroatom-substituted
[(ArO)2Ti(g
2–C2H4)(PMe3)] (ArO = 2,6-diphenylphenoxide) with
PhCH2N@CHPh afforded 2-azatitanacyclopentane, which could
couple with benzonitrile to produce 2,5-diazatitanacyclopent-2-
ene via the elimination of ethylene.5 However, the reaction suffers
from tedious multi-step formation of diazatitanacycles. Sato et al.
reported that a divalent titanium reagent generated by Ti(OiPr)4/
i
2 Pr MgX system reacted with arylaldimine to provide the corre-
sponding (
propionitrile to give a-aminoketone by quenching the resulting
g
2–imine)Ti(OiPr)2 complex, that in turn reacted with
p
-system such as aldehydes, ketones, imines, nitriles, and so on,
because it is difficult to synthesize the key intermediates of tita-
nium-heteroatom containing
-complexes.3–6 Recently our group
diazatitanacyclopentene.6 Although the reaction proceeded with
a good yield, only one successful example appeared in this report
by using N-alkyl substituted imine and aliphatic nitrile (PhCH@
NnPr and EtCN). These situations prompted us to study the
cross-coupling reactions of imines with nitriles by using Ti(OiPr)4/
2 c-C5H9MgCl reagent. In this Letter, we describe the synthesis of
p
initiated a research program to study the synthesis and reactivity
of titanium–imine complexes.4 We have successfully developed a
reductive cross-coupling reactions of imines with ketones or alde-
hydes via activation of imines with Ti(OiPr)4/2 c-C5H9MgCl
reagent7 leading to 1,2-amino alcohols.4a We have also investi-
gated titanium-mediated cross coupling reactions of imines with
terminal alkynes.4b However, until now the titanium-mediated
reductive cross-coupling reactions of imines with other
biologically relevant molecules, a
-aminoketone8 and 1,2-diketones,9
via titanium-mediated coupling reactions of imines with nitriles
under different quenching conditions (Scheme 1).
First, a typical example for the titanium-mediated synthesis of
a-aminoketone 4a was studied by using N-benzylidenebenzen-
amine 1a and benzonitrile as model substrates (Table 1, entry 1).
⇑
Corresponding author. Tel.: +86 21 54925135; fax: +86 21 64166128.
Based on our previous Letter,4 Ti–imine complex 2a was generated
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