Strongly electron-releasing substituents, such as in 3,5-dime-
thoxyaniline (Table 1, entries 7–8), led to slightly increased
yields, as compared to methyl groups in the same position
(entries 5–6). On the other hand, 3,5-bis(trifluoromethyl)aniline
could not be added to any cyanoolefin under the same
conditions. A strongly coordinating solvent such as acetonitrile
has a negative effect on the catalytic activity. Acetonitrile is
probably competing with the cyanoolefin as ligand for Ni.
The activities observed for our Ni catalyst are comparable to
or better than those previously reported for Pd catalysts,11 for
which generally higher temperatures and longer reaction times
are required. However, the enantioselectivities obtained are
generally low and for the substrate combinations of Table 1
reach only ca. 25% ee. Whereas the presence of a source of H+
was necessary for previously reported systems,13 in the case of
the Ni-catalysed reaction the addition of TfOH led to complete
catalyst deactivation and no reaction was observed.
Encouraged by the results obtained with anilines, we turned
our attention to aliphatic amines, in particular morpholine and
piperidine, and investigated their catalytic addition to activated
olefins (Scheme 3). As expected, the catalytic activities
observed in this case were higher than with anilines. Table 2
summarises the results obtained for reactions of aliphatic
amines with acrylic acid derivatives. Using 5 mol% catalyst the
addition of the selected aliphatic amines to crotonitrile,
methacrylonitrile, methyl acrylate, and methyl or ethyl croto-
nate afforded good to excellent isolated yields of the corre-
sponding product, again working at room temperature and with
a reaction time of not more than 24 h. The most remarkable
example (Table 2, entry 2) concerns the hydroamination of
methacrylonitrile with morpholine that gave the product in
quantitative yield and 69% ee. This is one of the still rare
example of an asymmetric hydroamination reaction charac-
terised by both relatively high catalytic activity and enantiose-
lectivity.14 Previous examples were additions of anilines
reported either by Hartwig using Pd catalysts or by us with the
Ir/fluoride system (80% yield and 81% ee for p-trifluoromethyl-
styrene,8 83% yield and 95% ee for cyclohexadiene,9 and 22%
yield and 95% ee for norbornene5). Crotonates add morpholine
quite effectively (Table 2, entries 6–7), however, no chiral
induction was observed.
The results obtained with our Ni catalyst are very encourag-
ing because they concerns olefins that have not yet been
investigated from the point of view of asymmetric hydro-
3
amination and because they are substrates for which an h -
allylic intermediate is not accessible.8,9 We are currently
pursuing modifications of the Pigiphos ligand framework with
a view to improving the enantioselectivity of the hydro-
amination reactions reported here.
This work was supported by the Swiss National Science
Foundation.
Notes and references
†
General procedure for the nickel-catalysed addition of aniline to
activated olefins: Ni(ClO4)2·6H2O (22.5 mg, 0.06 mmol), Pigiphos (0.54 ml
of a 0.1105 M standard solution in THF, 0.06 mmol), aniline (112 ml, 1.23
mmol) and crotonitrile (0.2 ml, 2.46 mmol) were dissolved in 2 ml THF.
The reaction mixture was stirred at r.t. for 24 h. The product was isolated by
silica gel column chromatography (5+1 hexane+ethyl acetate) to give 179.2
mg (91%) of 2-anilinopropyl cyanide. The enantioselectivity was deter-
mined by GC on a chiral stationary phase (a-cyclodextrin, 120 °C iso, tR
=
20
116.3 min and 118.5 min), [a]D = +18.88 (c = 1 in CHCl3).
General procedure for the nickel-catalysed addition of morpholine to
activated olefins: Ni(ClO4)2)·6H2O (22.5 mg, 0.06 mmol), Pigiphos (0.906
ml of a 0.0662 M standard solution in THF, 0.06 mmol), morpholine (107
ml, 1.23 mmol) and methacrylonitrile (0.2 ml, 2.46 mmol) were dissolved in
2 ml THF. The reaction mixture was stirred at r.t. for 24 h. The product was
isolated by silica gel column chromatography (1+1 hexane+ethyl acetate +
5% NEt3) to give 189 mg (99%) of 1-methyl-2-morpholinoethyl cyanide.
The enantioselectivity was determined by GC on a chiral stationary phase
20
(b-cyclodextrin, 92 °C iso, tR = 139.2 min and 142.7 min), [a]D
=
223.78 (c = 1 in CHCl3).
‡ Josiphos
=
(R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyldicyclo-
hexylphosphine and Pigiphos12 = (bis((S)-1-[(R)-2-(diphenylphosphino-
Scheme 3 Catalytic addition of aliphatic amines to activated olefins.
Table 2 Hydroamination with aliphatic amine
)ferrocenyl]ethyl)cyclohexylphosphine.
Entry Amine
1
Olefin
Conditionsa
Yieldb
99%
eec
rac
rac
1 J. J. Brunet and D. Neibecke, in Catalytic Heterofunctionalization, ed.
A. Togni and H. Grützmacher, VCH, Weinheim, 2001, pp. 91–141.
2 D. Steinborn and R. Z. Taube, J. Mol. Catal., 1989, 49, 235.
3 T. Müller and M. Beller, Chem. Rev., 1998, 98, 675 and references
therein.
r.t., 24 h, 5% cat.
r.t., 24 h, 1% cat.
62%
4 J. J. Brunet, G. Commenges, D. Neibecker and K. Philippot, J.
Organomet. Chem., 1994, 469, 221; M. Beller, H. Trauthwein, M.
Eichberger, C. Breindl and T. Müller, Eur. J. Inorg. Chem., 1999, 1121;
A. L: Casalnuovo, J. C. Calabrese and D. Milstein, J. Am. Chem. Soc.,
1988, 110, 6738.
2
r.t., 24 h, 5% cat.
99%
69%d
3
4
r.t., 24 h, 5% cat.
r.t., 24 h, 5% cat.
85%
99%
7%
5
Dorta, P. Egli, F. Zürcher and A. Togni, J. Am. Chem. Soc., 1997, 119,
10857.
6 C. Cao, J. T. Ciszewski and A. L. Odom, Organometallics, 2001, 20,
5011; L. Ackermann and R. G. Bergman, Org. Lett., 2002, 4, 1475; E.
Haak, H. Siebenreicher and S. Doye, Org. Lett., 2000, 2, 1935 and
references therein.
20%
5
6
7
r.t., 24 h, 5% cat.
r.t., 24 h, 5% cat.
r.t., 24 h, 5% cat.
70%
63%
77%
7 S. Tian, V. M. Arredondo, C. L. Stern and T. J. Marks, Organometallics,
1999, 18, 2568.
8 M. Kawatsura and J. F. Hartwig, J. Am. Chem. Soc., 2000, 122, 9546; U.
Nettekoven and J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 1166.
9 J. Pawlas, Y. Nakao, M. Kawatsura and J. F. Hartwig, J. Am. Chem.
Soc., 2002, 124, 3670; O. Löber, M. Kawatsura and J. F. Hartwig, J. Am.
Chem. Soc., 2001, 123, 4366.
rac
rac
10 H. M. Senn, P. Blöchl and A. Togni, J. Am. Chem. Soc., 2000, 122,
4098.
11 M. Kawatsura and J. F. Hartwig, Organometallics, 2001, 20, 1960.
12 P. Barbaro and A. Togni, Organometallics, 1995, 14, 3570.
13 A. L. Seligson and W. C. Trogler, Organometallics, 1993, 12, 744.
14 M. Nobis and B. Driessen-Hölscher, Angew. Chem., Int. Ed., 2001, 40,
3983.
a Reactions in THF, under inert conditions, catalyst: in situ generated
[Ni(PPP)(THF)](ClO4)2. b Yields are for isolated material after FC.
c Enantioselectivity determined by GC or HPLC analysis. d The results are
an average of 3 runs.
CHEM. COMMUN., 2003, 30–31
31