Prolina : pospolity aminokwas wyjątkowy katalizator. Część IV, Reakcja Michaela Proline as a common amino acid and an exceptional catalyst. Part IV, Michael reaction
In recent years there has been a dynamic development of asymmetric synthesis.
Groups of researchers, particularly the one led by Benjamin List and Carlos Barbas, carried
out a number of reactions and showed the effectiveness of the use of small organic
molecules such as proline as catalysts. Michael addition catalyzed with proline is a particularly
interesting reaction because it can be carried out in two aminocatalytic pathways.
The analysis of Michael reaction reveals potential for both forms of aminocatalysis:
enamine and iminium catalysis (Scheme 1) [1–14]. Presumably Michael reaction proceeds
mainly according to enamine mechanism. The use of proline in Michael reaction
with imine activated acceptor is slightly effective. So far the researches have shown that
the modification of proline molecule or addition of other catalyst is necessary for condensation
to appear. Enamine catalysis concerns the activation of carbonyl compound in situ
being a donor. There is no need for enolase anion to be created earlier [2, 15–17]. When,
as a result of the reaction of a,b-unsaturated carbonyl compound with proline, Michael
acceptor activation appears it means that it is enamine mechanism reaction (Scheme 1)
[2, 24]. One of the first examples of direct Michael reaction proceeding through enamine
transition state is the reaction of cyclopentanone with nitrostyrene (Scheme 6) [20–23].
Other examples of Michael addition of ketone with nitro olefin catalysed by proline are
shown in table 2 and 3 [10, 23, 30]. Nitroketones obtained in that way are useful as
precursors for different organic compounds [33], also pyrrolidines
[34]. Pyrrolidines are
pharmacologically active and they selectively block presynaptic dopamine receptors [34]
(Scheme 7).
Except for Michael intermolecular reaction, intramolecular condensation adducts
were also obtained. Michael intramolecular proline-catalyzed condensation in which
inactive ketones transform into α,β-unsaturated carbonyl compounds was described
(Scheme 9) [35, 36]. These reactions require a stoichiometric amount of a catalyst and
a long time of reaction and they give as a result a little enantiomeric excess [11, 24, 35].
In 1991, Yamaguchi and co-workers carried out malonates Michael addition to
α,
β-unsaturated aldehydes catalyzed by L-proline [24, 39]. The reaction proceeded
according to enamine mechanism, for example dimethyl malonate was reacted with hex-
2-enal in the presence of proline to give Michael adduct in 44% yield. To improve the yield
an attempt of a slight modification of a proline molecule was made transforming it into
proper salt. Proline lithium salt enabled to obtain the condensation product in 93% yield
(Tab. 4). Regardless of a used catalyst the products in the form of racemates were obtained.
In order to improve enantioselective properties of a catalyst, Michael addition of
diisopropyl malonate to cycloheptenone was carried out in chloroform in the presence
of different proline salts. Optimal enantioselectivity and yield was obtained by using rubidium
salt (Tab. 5–7) [40, 41].
Rubidium prolinate-catalyzed Michael additions are used in industry e.g. for enantioselective
synthesis of the selective serotonine reuptake inhibitior (SSRI) (–)-paroxetine
(antidepressant) (Scheme 12) [24].
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