Enantioselective conjugate addition of diethylzinc using catalytic silver(I) diaminocarbenes and Cu(OTf)2

Article abstract of DOI:10.1016/S0957-4166(01)00325-1

Chiral silver(I) diaminocarbenes act as efficient carbene transfer agents to copper salts. The catalytic species, active in the conjugate addition of diethylzinc to cyclohexenone, is prepared easily at room temperature in various solvents by simply mixing

Full text of DOI:10.1016/S0957-4166(01)00325-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 2087–2089
Enantioselective conjugate addition of diethylzinc using catalytic
silver(I) diaminocarbenes and Cu(OTf)2
Julien Pytkowicz, Sylvain Roland* and Pierre Mangeney
Laboratoire de Chimie des Organo e´ l e´ ments, UMR 7611, Universit e´ P. et M. Curie, 4, Place Jussieu, tr 44-45, 2 e` me e´ t,
75252 Paris cedex 05, France
Received 6 July 2001; accepted 15 July 2001
Abstract—Chiral silver(I) diaminocarbenes act as efficient carbene transfer agents to copper salts. The catalytic species, active in
the conjugate addition of diethylzinc to cyclohexenone, is prepared easily at room temperature in various solvents by simply
mixing the silver carbene and Cu(OTf) . This method avoids the use of strong bases and polar solvents to generate the carbene.
2
The chiral diaminocarbene–copper catalyst, formed in situ, shows a strong accelerating effect and gives enantiomeric excesses up
to 23%. © 2001 Elsevier Science Ltd. All rights reserved.
4
N-Heterocyclic carbenes have recently emerged as an
catalysts for C–C coupling reactions. Syntheses and
structures of N-functionalised silver(I) carbene com-
plexes derived from imidazolium salts were also
important family of ligands with electronic characteris-
1
tics similar to those of the phosphines. The use of
5
imidazol-2-ylidene, thiazol-2-ylidene and imidazolidin-
reported by Danopoulos et al. in 2000.
2
-ylidene metal complexes rapidly showed an increased
interest since it was demonstrated that they are efficient
catalysts in important chemical transformations, such
as Ni and Pd carbon–carbon coupling reactions, CO-
ethylene copolymerisations, Ru-catalysed olefins
metathesis and Rh catalyzed hydrosilylations. Initially,
the widespread use of catalysts with carbene ligands
was limited due to their relatively difficult preparation.
The first syntheses have utilized the free carbenes,
obtained by deprotonation of the corresponding
azolium salts, which are extremely air and moisture
sensitive. Recent investigations have demonstrated that
the free carbenes can be generated and directly trapped
Such an approach is mild and compatible with the
presence of acidic protons in chains of the azolium salts
and we recently reported that chiral silver(I)
diaminocarbenes can also be easily obtained from the
6
less acidic imidazolinium precursors and Ag O. This
2
provided a very convenient method for the formation
of chiral carbene complexes by overcoming many of the
difficulties arising from the use of strong bases.
Copper(I) carbene complexes derived from imidazolium
salts were synthesized and characterized for the first
time by Arduengo in 1993 by reaction of the free
2
7
in situ (Scheme 1).
carbene with copper triflate. In 2001, Woodward et al.
reported the first ligand accelerated catalysis with an
In 1998, Wang and Lin showed that a silver benzimida-
zol-2-ylidene complex could be easily obtained by treat-
3
ment of the corresponding azolium salt with Ag O.
2
Moreover, this silver carbene complex acts as an effec-
tive carbene transfer agent for the synthesis of palla-
dium or gold carbene complexes (Scheme 1). This
methodology was applied recently with success by
McGuinness and Cavell towards the synthesis of palla-
dium imidazol-2-ylidene complexes which are efficient
*
0
Corresponding author. Tel.: +33 (0) 1 44275567; fax: +33 (0) 1
4277567; e-mail: sroland@ccr.jussieu.fr
4
Scheme 1. Preparation of diaminocarbene–metal complexes.
957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00325-1

2
088
J. Pytkowicz et al. / Tetrahedron: Asymmetry 12 (2001) 2087–2089
Arduengo-type carbene in copper-catalyzed conjugate
rate of the reaction was still lower than with copper
triflate alone (11% conversion after 15 min).
8
10
addition. In their study, the diaminocarbene ligand 1
was not isolated but generated by deprotonation of the
t
precursor imidazolium salt by Bu OK in THF. This
The solvent-dependency of this reaction was studied
and the results are presented in Table 1. The accelerat-
ing effect of the diaminocarbene 2 was also very impor-
tant in hexane or diethylether and the rates of the
reaction are similar to these observed in toluene (Table
THF solution was then added to a solution of
Cu(OTf) to form the pre-catalytic copper species.
2
1
, entries 1–3). Nevertheless, the conjugate addition was
significantly slower in CH Cl since only 62% of con-
2
2
version was achieved after 1 h at 0°C (entry 4). A
dramatic decreasing of the reactivity was also observed
in THF (28% of conversion after 1 h) (entry 5). The
best e.e. (23%) was obtained in PhCH while Et O and
3
2
hexane gave similar excesses (15–16%) and no enan-
Synthesis and use of chiral diaminocarbene complexes
remains an important challenge for organic chemists
and only a few catalysts have been reported. Herein,
we report our first results on the enantioselective conju-
gate addition of diethylzinc to cyclohexenone using the
tioselectivity was observed in CH Cl and THF. The
2
2
9
reaction in toluene was still fast until a temperature of
40°C but was slowed down at −78°C (entries 6–8).
−
The more surprising result was the decrease in the e.e.
when the temperature was lowered (entries 1 and 6–8).
An e.e of only 4% was measured on the adduct
chiral silver(I) diaminocarbene 2 and Cu(OTf) . In our
2
studies, 2 was obtained by reaction of the correspond-
obtained at −78°C in PhCH , compared to 23% at 0°C.
3
ing chiral imidazolinium salt 3 and Ag O (0.5 equiv.) in
2
6
The major enantiomer in all these experiments was
CH Cl (Scheme 2) as previously reported. This com-
2
2
identical. Its absolute configuration (S) was determined
pound is a crystalline solid that can be isolated and
easily handled.
13
by C NMR after formation of the aminal with (R,R)-
11
1
,2-diphenyl-1,2-diaminoethane.
In our first experiment, the Ag(I) carbene 2 (2%) was
In conclusion, the chiral silver(I) diaminocarbene 2 acts
as efficient carbene transfer agent to copper(II) triflate.
The catalytic species, active in the conjugate addition of
diethylzinc to cyclohexenone, is prepared easily at room
temperature and in various solvents. This method
avoids the use of strong bases and polar solvents to
generate the carbene. The chiral diaminocarbene–cop-
per catalyst, formed in situ, shows a strong accelerating
effect and gives moderate enantiomeric excesses up to
dissolved in toluene at room temperature and Cu(OTf)2
(
2%) was added. A white precipitate appeared after
stirring for 5 min. The mixture was cooled to 0°C and
diethylzinc (1.5 equiv.) was added followed by cyclo-
hexenone. The conjugate adduct was obtained in less
than 30 min and a moderate e.e. of 23% was measured
on the isolated compound (Scheme 3).
The strong ligand accelerated catalysis (LAC) effect of
the silver carbene in the presence of Cu(OTf)2 was
examined by comparison with the same experiment, at
2
3%.
0
°C in PhCH , with Cu(OTf) alone (Fig. 1, graph B).
3 2
The reaction was slower and only a 22% conversion
was achieved after 15 min. We also checked that the
diaminocarbene did not catalyze the reaction in the
absence of Cu(OTf) (Fig. 1, graph A). In this case, the
2
Scheme 2. Synthesis of chiral silver(I) diaminocarbenes from
imidazolinium salts.
Figure 1. Ligand accelerated catalysis with the silver(I)
diaminocarbene 2 and copper(II) triflate in PhCH3 at 0°C.
Graph A: 2% diaminocarbene 2. Graph B: 2% Cu(OTf)2.
Graph C: 2% diaminocarbene 2+2% Cu(OTf) . The conver-
2
Scheme 3. Conjugate addition using 2 and Cu(OTf)2.
sions were determined by GC.

J. Pytkowicz et al. / Tetrahedron: Asymmetry 12 (2001) 2087–2089
Table 1. Influence of the temperature and solvent
2089
Entry
Solvent
Temperature (°C)
Time (h)
Yield (%)a
E.e (%)b
1c
2
3
4
5
6
7
8
PhCH3
Hexane
0
0
0
0
0
0.25
0.25
0.25
0.25 (1)
98
99
95
37 (62)
12 (28)
99
98
78
23
16
15
0
Et O
2
CH Cl
2
2
THF
0.25 (1)
0
PhCH3
PhCH3
PhCH3
−20
−40
−78
1
1
1
16
10
4
Typical procedure: A mixture of silver(I) diaminocarbene 2 (2% mol, 0.025 mmol) and Cu(OTf) (2% mol, 0.025 mmol) in the appropriate solvent
2
(
5 ml) was stirred for 5 min at 20°C. To this suspension was added Et Zn (1.1 M in hexane, 1.87 mmol). The mixture was brought to the
2
appropriate temperature and cyclohexenone was added. The reaction was hydrolyzed with HCl 5N, extracted with ether, dried on MgSO4 and
concentrated. The crude was purified by silica-gel chromatography (pentane/Et O, 9:1).
Conversion determined by GC after quenching with HCl.
Determined by chiral GC (Lipodex E, 100°C).
2
a
b
c
The same experiment performed with 4% mol of 2 and 2% mol of Cu(OTf) led to identical results regarding the reaction rate and to a similar
2
ee of 20%.
Acknowledgements
4. (a) McGuinness, D. S.; Cavell, K. J. Organometallics
000, 19, 741; (b) Magill, A. M.; McGuinness, D. S.;
2
Cavell, K. J.; Britovsek, G. J. P.; Gibson, V. C.; White,
A. J. P.; Williams, D. J.; White, A. H.; Skelton, B. W. J.
Organomet. Chem. 2001, 617–618, 546.
J. Pytkowicz thanks the MESR for a grant. We thank
Professor A. Alexakis and Professor J.-F. Normant for
helpful discussion.
5
. Tulloch, A. A. D.; Danopoulos, A. A.; Winston, S.;
Kleihenz, S.; Eastham, G. J. Chem. Soc., Dalton Trans.
2
000, 4499.
References
6
7
8
. Pytkowicz, J.; Roland, S.; Mangeney, P. J. Organomet.
Chem. 2001, in press.
. Arduengo, A. J.; Dias, H. W. R.; Calabrese, J. C.;
Davidson, F. Organometallics 1993, 12, 3405.
. (a) Fraser, P. K.; Woodward, S. Tetrahedron Lett. 2001,
1
. For recent reviews, see: (a) Herrmann, W. A.; K o¨ cher, C.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2162; (b) Bourris-
sou, D.; Guerret, O.; Gabba ¨ı , F. P.; Bertrand, G. Chem.
Rev. 2000, 100, 39.
. (a) Herrmann, W. A.; Reisinger, C.-P.; Spiegler, M. J.
Organomet. Chem. 1998, 557, 93; (b) Zhang, C.; Huang,
J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64,
804; (c) Cal o` , V.; Del Sole, R.; Nacci, A.; Schingaro, E.;
Scordari, F. Eur. J. Org. Chem. 2000, 869; (d) Cal o` , V.;
Nacci, A.; Lopez, L.; Mannarini, N. Tetrahedron Lett.
4
2, 2747; (b) The LAC effects in conjugate addition was
2
demonstrated first by Alexakis et al. in 1993 using phos-
phine ligands, see: Alexakis, A.; Frutos, J. C.; Mangeney,
P. Tetrahedron: Asymmetry 1993, 4, 2427–2430.
. See in reviews Refs. 1a and 1b and: (a) Lappert, M. F. J.
Organomet. Chem. 358 1988, 358, 185; (b) Scholl, M.;
Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 6,
3
9
2
2
000, 41, 8973; (e) Lee, H. M.; Nolan, S. P. Org. Lett.
000, 14, 2053; (f) Morgan, J. P.; Grubbs, R. H. Org.
9
53; (c) Clyne, D. S.; Jin, J.; Genest, E.; Gallucci, J. C.;
RajanBabu, T. V. Org. Lett. 2000, 2, 1125; (d) Lee, S.;
Hartwig, J. F. J. Org. Chem. 2001, 66, 3402; (e) Huang,
J.; Jafarpour, L.; Hillier, A. C.; Stevens, E. D.; Nolan, S.
P. Organometallics 2001, 20, 2878.
Lett. 2000, 20, 3153.
. (a) Wang, H. M. J.; Lin, I. J. B. Organometallics 1998,
3
1
7, 972; (b) Polymeric silver(I) diaminocarbenes were also
previously prepared by treatment of triazolium salts with
silver(I) acetate in refluxing THF, see: Guerret, O.; Sol e´ ,
S.; Gornitzka, H.; Teichert, M.; Trinquier, G.; Bertrand,
G. J. Am. Chem. Soc. 1997, 119, 6668.
10. A very low ee of 1% was measured in this reaction.
11. Alexakis, A.; Frutos, J. C.; Mangeney, P. Tetrahedron:
Asymmetry 1993, 4, 2431–2434.