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Topics in Current Chemistry (2020) 378:1
obtainment of the R-configurated aldol products. Their rationale suggested that
metal Cu(II) serves as a Lewis acid activating the aldehyde, and the pyrrolidine ring
base generates the reactive enamine intermediate. Raiser, while exploring another
compatible Lewis acid, described the catalytic system formed by the combination
of CoCl 2 and l-proline (1:2) [67]. The system was found to be an excellent catalyst for the aldol reactions of cyclic ketones and acetone with aldehydes in MeOH
(Scheme 4). The results were excellent in terms of yields (up to 93%) and ees (99%
ee). Furthermore, the system showed a remarkable diastereoselectivity (anti/syn up
to 45:1) compared to the use of proline as the sole catalyst. It is important to mention that it was possible to apply the catalytic system also with aliphatic aldehydes
(isopropyl and cyclohexyl).
The authors have assumed the formation of an octahedral cobalt complex, which
upon the liberation of HCl in solution, forms the key enamine (Scheme 4). In the
examples discussed above, the authors have taken advantage of the proline moiety in
the design of the catalytic system. Wang introduced a class of primary amine-metal
Lewis acid bifunctional catalysts based on a simple bidentate ligand (Scheme 5)
[68].
The catalyst was simply prepared by the coupling reactions between N-Boc protected l-amino acids and 2-aminopyridine followed by deprotection. The pyridine
moiety was introduced with the aim to coordinate a Lewis acid, and to bring in
proximity the metal center and the enamine formed with the primary amine. Guided
by the work previously commented in this review, the authors have investigated
Cu(SbF 6 ) 2 as a Lewis acid and they have established the optimal ligand-to-metal
ratio (2:1). Other metals were examined (Co, Zn, Yb) but gave inferior results. The
reaction was carried out with a variety of aldehydes in neat conditions, affording
the desired aldol products in good yields and stereoselectivities. It is important to
Scheme 4 Direct aldol reactions of cyclic ketones with aldehydes catalyzed by cobalt/proline in MeOH
Reprinted from the journal
39
Topics in Current Chemistry (2020) 378:1
obtainment of the R-configurated aldol products. Their rationale suggested that
metal Cu(II) serves as a Lewis acid activating the aldehyde, and the pyrrolidine ring
base generates the reactive enamine intermediate. Raiser, while exploring another
compatible Lewis acid, described the catalytic system formed by the combination
of CoCl 2 and l-proline (1:2) [67]. The system was found to be an excellent catalyst for the aldol reactions of cyclic ketones and acetone with aldehydes in MeOH
(Scheme 4). The results were excellent in terms of yields (up to 93%) and ees (99%
ee). Furthermore, the system showed a remarkable diastereoselectivity (anti/syn up
to 45:1) compared to the use of proline as the sole catalyst. It is important to mention that it was possible to apply the catalytic system also with aliphatic aldehydes
(isopropyl and cyclohexyl).
The authors have assumed the formation of an octahedral cobalt complex, which
upon the liberation of HCl in solution, forms the key enamine (Scheme 4). In the
examples discussed above, the authors have taken advantage of the proline moiety in
the design of the catalytic system. Wang introduced a class of primary amine-metal
Lewis acid bifunctional catalysts based on a simple bidentate ligand (Scheme 5)
[68].
The catalyst was simply prepared by the coupling reactions between N-Boc protected l-amino acids and 2-aminopyridine followed by deprotection. The pyridine
moiety was introduced with the aim to coordinate a Lewis acid, and to bring in
proximity the metal center and the enamine formed with the primary amine. Guided
by the work previously commented in this review, the authors have investigated
Cu(SbF 6 ) 2 as a Lewis acid and they have established the optimal ligand-to-metal
ratio (2:1). Other metals were examined (Co, Zn, Yb) but gave inferior results. The
reaction was carried out with a variety of aldehydes in neat conditions, affording
the desired aldol products in good yields and stereoselectivities. It is important to
Scheme 4 Direct aldol reactions of cyclic ketones with aldehydes catalyzed by cobalt/proline in MeOH
Reprinted from the journal
39