Tetrahedron Letters
Nucleophilic addition of TMSCCl to N-phosphinoyl benzaldimines:
3
a route to N-phosphinoyl-
a-(trichloromethyl)benzylamines
⇑
Benoit Wahl, Albert Cabré, Simon Woodward , William Lewis
School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Nucleophilic addition of readily available TMSCCl to N-phosphinoyl benzaldimines allows preparation of
3
Received 16 July 2014
Revised 13 August 2014
Accepted 28 August 2014
Available online 6 September 2014
N-phosphinoyl-a-(trichloromethyl)benzylamines. Typically, the reaction in THF at room temperature
using tetrabutylammonium difluorotriphenylsilicate (TBAT) as a catalytic promoter, afforded very good
yields (65–95% range) for most derivatives within 1 h at room temperature.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Trichloromethylation
Fluoride catalysis
Imine
1
,2-Addition
a
-Trichloromethylamines are interesting biologically active
We initially investigated the nucleophilic reaction of TMSCCl
with (E)-N-benzylidene-P,P-diphenylphosphinic amide (1a)
(Table 1). Initial trials revealed that TMSCCl requires activation
by a silylphilic promoter; the fluoride ion from TBAT (tetrabutyl-
ammonium difluorotriphenylsilicate) was most effective here
(run 1 vs run 2). Further investigation showed that the reaction
could be efficiently carried out in THF at room temperature within
an hour, using only 1 mol % of TBAT (run 2 vs runs 3 and 4). Insol-
uble CsF was poorly effective (run 5). The diphenylphosphinoyl
benzaldimine starting materials 1 are accessed by titanium(IV)
3
compounds used as: herbicides, insecticides2 or fungicides, and
1
3
more recently have revealed dopaminergic neurotoxicity proper-
3
4
ties. They also represent a key intermediate in the synthesis
5
of valuable organic molecules such as,
and
2-chloroethynyl)amines and 2,2-dichloroaziridines and enami-
a,a-dichloroimines
a
-trichloromethyl imines,6 2,2-dichlorovinylamines and
7
7,8
(
9
no esters.
a-Trichloromethylamines are directly synthesised by
nucleophilic addition of a trichloromethyl anion equivalent to an
imine. A few different sources of CCl
À
3
can be used: trichloroacetic
1
0
8,11
12
acid, chloroform
trichloroacetic acid is limited by harsh decarboxylation conditions
while the use of CHCl requires strong bases (t-BuOK and NaH-
MDS). Conversely, TMSCCl only requires activation by a silylphilic
promoter, typically a fluoride ion. Following our recent improve-
ments on the synthesis of TMSCCl
(70% isolated yield),13 we aimed
to extend the use of this reagent to imines. Present nucleophilic
reactions of TMSCCl with imines are limited to very few
examples: a low yielding (34%) 1,2-addition to a salicylaldi-
mine, using an intramolecular activation of the imine through
chelation of boron trifluoride etherate with the adjacent hydroxyl
group,
N-(tert-butylsulfinyl)aldimines.
dented nucleophilic addition of TMSCCl
benzaldimines would be an efficient route to useful
N-phosphinoyl- -(trichloromethyl)benzylamines.
or trimethyl(trichloromethyl)silane. Use of
3
Table 1
Optimisation of TMSCCl
addition to 1aa
3
3
O
PPh2
O
PPh2
3
TMSCCl3
(1.5 equiv.)
N
HN
3
Promoter
THF
CCl3
1
a
2a
1
2a
and Li’s diastereoselective addition of TMSCCl
3
to
We conceived that unprece-
to diphenylphosphinoyl
12b,c
Run
Promoter
None
TBAT (1 equiv)
TBAT (10 mol %)
TBAT (1 mol %)
CsF
Temp (°C)
Time (h)
2aa (%)
1
2
3
4
5
rt
1–16
1
1
1
<5
>95
>90
>90 (89)
<10
3
À50
À50
rt
a
rt
1–16
a
Carried out on 1.0 mmol 1a (0.25 M); conversions to 2a determined by 1H NMR
⇑
spectroscopy; in run 4 the isolated yield of 2a is in parentheses.
040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
0