Tetrahedron: Asymmetry
Highly enantioselective conjugate addition of diethylzinc to enones using
aziridine-functionalized tridentate sulfinyl ligands
Michał Rachwalski a,b, Stanisław Le s´ niak a,*, Piotr Kiełbasi n´ ski
b,*
a
Department of Organic and Applied Chemistry, University of Łód ´z , Tamka 12, 91-403 Łód ´z , Poland
b
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Heteroorganic Chemistry, Sienkiewicza 112, 90-363 Łód ´z , Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 April 2010
Accepted 25 May 2010
Enantiomerically pure tridentate heteroorganic catalysts, containing hydroxyl, sulfinyl, and aziridine
moieties, have proven to be highly efficient in the enantioselective conjugate diethylzinc addition to chal-
cone and cyclohexenone to give the desired products in very high yields (up to 95%) and with ee’s up to
93%. The influence of the stereogenic centers located on the sulfinyl sulfur atom and in the aziridine moi-
ety on the stereochemical course of the reaction is discussed.
Ó 2010 Elsevier Ltd. All rights reserved.
1
. Introduction
cannot be neglected, since the reaction is stereoselective even if
the ligand bears an achiral aziridine moiety.
Enantioselective carbon–carbon bond formation using organo-
On the other hand, the asymmetric 1,4-addition of diethylzinc
to enones also requires, in addition to a chiral ligand, a metal cat-
alyst. The two additives co-operate both in the formation of a chiral
chelate and in the appropriate coordination of diethylzinc and the
enone. The most commonly used metal catalysts are derivatives of
zinc reagents has become one of the most successful areas of asym-
1
metric synthesis in recent years. Among the reactions applied, the
addition of diethylzinc to carbonyl compounds (proceeding in a
,2-fashion) and to enones (a 1,4-addition) are the model reactions
that, besides their practical applications, are commonly used for
the evaluation of the effectiveness and the stereoselectivity of
newly developed chiral ligands and catalysts.
1
6
1,7,8
2 2 2
nickel (e.g., Ni(acac) ) and copper (e.g., Cu(OTf) or Cu(OAc) ).
1
Among the chiral ligands, again various aminoalcohols are the
main types, complemented by their derivatives bearing additional
8
The last comprehensive overview concerning the former type of
functional groups, for example, aminohydroxyphosphines. Other
2
addition was in 2001, and has been followed by a number of new
types of substituted alcohols and amines have also been used,
7
,9
original reports. An inspection of the types of compound that exhi-
bit the best catalytic activity in this reaction clearly shows that the
most efficient ones are chiral aminoalcohols, although some other
types of catalysts, bearing various chelating groups, have also been
used. We have recently reported a chemoenzymatic synthesis of
chiral tridentate ligands, having hydroxyl, sulfinyl, and amine moi-
eties, with two stereogenic centers, the one located on the sulfinyl
sulfur atom and the other on the carbon atom in the amine moi-
including thiol and mercapto analogs of BINOL and phospho-
rus-containing derivatives, for example, phosphoroamidites.1
Taking this into account, we have decided to determine the scope
of applicability of our tridentate ligands by using them as catalysts
for the conjugate addition of diethylzinc to enones.
,10
2
. Results and discussion
3
ety. The ligands have proven to be versatile catalysts for various
Having in mind that the best results of the diethylzinc addition
stereoselective reactions: those bearing open-chain chiral amines
to aldehydes were obtained using ligands which contained chiral
4
5
for the nitroaldol (Henry) reaction, while those bearing chiral azir-
aziridine moieties, the following four ligands were applied
idines 1—for the enantioselective diethylzinc addition to alde-
(Scheme 1).
5
hydes. Each enantiomer of the product may be obtained by
Ligands 1b and 1c bear the aziridinyl groups which originate
using easily available diastereomeric ligands. The stereogenic cen-
ters located on the amine/aziridine moieties have been found to
exert a decisive influence on the absolute configuration of the
products, although the influence of the sulfinyl stereogenic center
from both enantiomers of 2-iso-propylaziridine b and c. The reason
for using them was to determine the possible match–mismatch
effect of both stereogenic centers and to evaluate which one plays
a decisive role in the stereoinduction. Ligand 1a, containing an
achiral aziridine a, was used to check whether the sulfinyl moiety,
being the only stereogenic center, exerts any influence on the
stereochemical course of the addition. Nickel acetylacetonate,
*
2
Ni(acac) was used as the metal catalyst and the ligands were
screened for their catalytic activity in the diethylzinc addition to