Topics in Current Chemistry (2020) 378:1
1 3
1,4-conjugate addition of branched aldehydes to α,β-unsaturated 2-acyl imidazoles
in the presence of a chiral-at-metal rhodium complex catalyst (Scheme 21b) with
a (S)-3-amino-3-phenylpropanoic acid (l-β-phenylalanine) as a the organocatalyst.
The proposed mechanism for the conjugate addition is shown in Scheme 21b. The
chiral amine is coordinated to the rhodium complex and it is released upon protonation. Two coordination sites of the rhodium complex are available, after the release
of the amine, for the activation of the 2-acyl imidazole substrate through a bidentate coordination. The free primary amine forms a chiral enamine reacting with the
branched aldehyde, which reacts with the Michael acceptor in an enantioselective
manner. It is also important to mention that the use of the other enantiomer of the
amine leads to the same major stereoisomer, showing that the stereoselection of the
reaction is principally controlled by the rhodium complex [124–126].
9 Reactions Developed Through Cooperative Iminium‑Lewis Acid
Catalysis
In iminium activation mode, the organocatalyst generates an electrophilic intermediate, and the Lewis acid needs to be compatible with the presence of nucleophiles and
needs to participate in their activation. It is possible to make a distinction between
the actions promoted by the Lewis acid. The Lewis acid, once again, can form an
electrophilic organometallic species. On the other hand, fruitful combinations of
Lewis acids and iminium catalysis were tested for sequential reactions. In the first
step, the iminium activation, realized with the organocatalyst, can enhance the electrophilicity of unsaturated carbonyl compounds towards the nucleophilic addition. In
the subsequent step, the Lewis acid induces other reactions, which are often cyclization reactions leading to cyclic products. Otherwise, it could activate the substrate
towards the reaction with a nucleophile.
Jørgensen reported an interesting reaction using the iminium activation mode,
combining organocatalysis and Lewis acids [127]. In this work, he showed the possibility to functionalize inactivated alkyl quinolines with alkyl groups in the presence of InCl 3 . Such metal salt used in catalytic amounts allowed the addition of alkyl
quinolines to α,β-unsaturated aldehydes activated by an organocatalyst (Scheme 22).
The reaction proceeds in a highly stereoselective manner through two cycles (Lewis
acid and iminium ion catalyzed) and harsh conditions.
Rios has reported the addition of benzoxazole to a Morita–Baylis–Hillman carbonate, to afford the alkyl-aza-arene in a diastereoselective manner (up to 15:1 dr)
and in good yields. The Morita–Baylis–Hillman carbonate is activated by DABCO
in the presence of a Lewis acid (10 mol% AgOAc). An example of the enantioselective variant of the reaction was inserted in the paper, and a chiral Cinchona alkaloid
was employed instead of a catalytic amount of DABCO. The enantio-enriched product was obtained in 50% ee and with a dr of 15:1 [128]. 1,3-Acetonedicarboxylic
acid was used as pro-nucleophile in an iminium activation mode [129]. The ketodiacid was activated by copper Lewis acid catalysis to give chiral cyclohexenones as
final products in one single step in 94–99% ee.
Reprinted from the journal
56
1 3
1,4-conjugate addition of branched aldehydes to α,β-unsaturated 2-acyl imidazoles
in the presence of a chiral-at-metal rhodium complex catalyst (Scheme 21b) with
a (S)-3-amino-3-phenylpropanoic acid (l-β-phenylalanine) as a the organocatalyst.
The proposed mechanism for the conjugate addition is shown in Scheme 21b. The
chiral amine is coordinated to the rhodium complex and it is released upon protonation. Two coordination sites of the rhodium complex are available, after the release
of the amine, for the activation of the 2-acyl imidazole substrate through a bidentate coordination. The free primary amine forms a chiral enamine reacting with the
branched aldehyde, which reacts with the Michael acceptor in an enantioselective
manner. It is also important to mention that the use of the other enantiomer of the
amine leads to the same major stereoisomer, showing that the stereoselection of the
reaction is principally controlled by the rhodium complex [124–126].
9 Reactions Developed Through Cooperative Iminium‑Lewis Acid
Catalysis
In iminium activation mode, the organocatalyst generates an electrophilic intermediate, and the Lewis acid needs to be compatible with the presence of nucleophiles and
needs to participate in their activation. It is possible to make a distinction between
the actions promoted by the Lewis acid. The Lewis acid, once again, can form an
electrophilic organometallic species. On the other hand, fruitful combinations of
Lewis acids and iminium catalysis were tested for sequential reactions. In the first
step, the iminium activation, realized with the organocatalyst, can enhance the electrophilicity of unsaturated carbonyl compounds towards the nucleophilic addition. In
the subsequent step, the Lewis acid induces other reactions, which are often cyclization reactions leading to cyclic products. Otherwise, it could activate the substrate
towards the reaction with a nucleophile.
Jørgensen reported an interesting reaction using the iminium activation mode,
combining organocatalysis and Lewis acids [127]. In this work, he showed the possibility to functionalize inactivated alkyl quinolines with alkyl groups in the presence of InCl 3 . Such metal salt used in catalytic amounts allowed the addition of alkyl
quinolines to α,β-unsaturated aldehydes activated by an organocatalyst (Scheme 22).
The reaction proceeds in a highly stereoselective manner through two cycles (Lewis
acid and iminium ion catalyzed) and harsh conditions.
Rios has reported the addition of benzoxazole to a Morita–Baylis–Hillman carbonate, to afford the alkyl-aza-arene in a diastereoselective manner (up to 15:1 dr)
and in good yields. The Morita–Baylis–Hillman carbonate is activated by DABCO
in the presence of a Lewis acid (10 mol% AgOAc). An example of the enantioselective variant of the reaction was inserted in the paper, and a chiral Cinchona alkaloid
was employed instead of a catalytic amount of DABCO. The enantio-enriched product was obtained in 50% ee and with a dr of 15:1 [128]. 1,3-Acetonedicarboxylic
acid was used as pro-nucleophile in an iminium activation mode [129]. The ketodiacid was activated by copper Lewis acid catalysis to give chiral cyclohexenones as
final products in one single step in 94–99% ee.
Reprinted from the journal
56