1 3
Topics in Current Chemistry (2018) 376:46
chemical and stereochemical efficiency. The supported catalyst was tested for the
continuous flow synthesis of enantioenriched amines 14a,b (Scheme 7) in good
yields and enantioselectivity. Remarkably, amine 14b is an immediate precursor of
pharmaceutically relevant molecules such as rivastigmine, the calciomimetic (R)NPS 568, and acrylamide (S)-A.
A polystyrene-supported 9-amino(9-deoxy)epi quinine has been developed by
Pericàs in 2015 and used in enantioselective Michael reactions involving stabilized
nucleophiles and enones [42]. The robustness and versatility of the supported catalyst was tested under traditional batch conditions first, and subsequently in singlepass packed-bed flow reactors (Scheme 7). The supported catalyst 15a could operate for 21 h without affecting the enantioselectivity. By using 500 mg of supported
catalyst, and a residence time of 40 min, a library of adducts 16a–f was prepared.
Interestingly, compounds 16b–f were obtained using a “wash and run” approach.
The solutions of enone, nucleophile, and the benzoic acid were consecutively circulated through the system at 50 μl/min every 2 h, while the column was washed with
CHCl 3 for 1 h between two consecutive runs. Supported quinine 15b was reported
by Puglisi, and used in batch mode, proving efficiency and robustness. A continuous
flow packed-bed reactor was also set up and used for a single example of Michael
reaction leading to adduct 16g in good yield and enantioselectivity (Scheme 8) [43].
A polymer-supported bifunctional thiourea was developed by Pericàs’ group
using a simplified approach avoiding the use of linkers/spacers [44]. This supported
catalyst was employed either in batch or in a packed-bed reactor in the α-amination
of 1,3-dicarbonyl compounds at room temperature, disclosing that basic washings
between runs allowed for an effective recycling of the supported catalyst. The implementation of a continuous flow process, based on supported thiourea 17 (Scheme 9)
furnished adduct 18 with high enantioselectivity (er > 97:3), running the flow system for 7.5 h and collecting 1.81 g of product.
Polystyrene-supported squaramide has also been developed and used in packedbed continuous flow reactors for performing enantio-selective Michael-type reactions between 2-hydroxy-1,4-naphthoquinone and nitroalkenes [45]. The supported
catalyst 19 could be recycled up to ten times under batch conditions and used
Scheme 7 Reduction of imines with trichlorosilane in a packed-bed flow reactor
37
Reprinted from the journal
Topics in Current Chemistry (2018) 376:46
chemical and stereochemical efficiency. The supported catalyst was tested for the
continuous flow synthesis of enantioenriched amines 14a,b (Scheme 7) in good
yields and enantioselectivity. Remarkably, amine 14b is an immediate precursor of
pharmaceutically relevant molecules such as rivastigmine, the calciomimetic (R)NPS 568, and acrylamide (S)-A.
A polystyrene-supported 9-amino(9-deoxy)epi quinine has been developed by
Pericàs in 2015 and used in enantioselective Michael reactions involving stabilized
nucleophiles and enones [42]. The robustness and versatility of the supported catalyst was tested under traditional batch conditions first, and subsequently in singlepass packed-bed flow reactors (Scheme 7). The supported catalyst 15a could operate for 21 h without affecting the enantioselectivity. By using 500 mg of supported
catalyst, and a residence time of 40 min, a library of adducts 16a–f was prepared.
Interestingly, compounds 16b–f were obtained using a “wash and run” approach.
The solutions of enone, nucleophile, and the benzoic acid were consecutively circulated through the system at 50 μl/min every 2 h, while the column was washed with
CHCl 3 for 1 h between two consecutive runs. Supported quinine 15b was reported
by Puglisi, and used in batch mode, proving efficiency and robustness. A continuous
flow packed-bed reactor was also set up and used for a single example of Michael
reaction leading to adduct 16g in good yield and enantioselectivity (Scheme 8) [43].
A polymer-supported bifunctional thiourea was developed by Pericàs’ group
using a simplified approach avoiding the use of linkers/spacers [44]. This supported
catalyst was employed either in batch or in a packed-bed reactor in the α-amination
of 1,3-dicarbonyl compounds at room temperature, disclosing that basic washings
between runs allowed for an effective recycling of the supported catalyst. The implementation of a continuous flow process, based on supported thiourea 17 (Scheme 9)
furnished adduct 18 with high enantioselectivity (er > 97:3), running the flow system for 7.5 h and collecting 1.81 g of product.
Polystyrene-supported squaramide has also been developed and used in packedbed continuous flow reactors for performing enantio-selective Michael-type reactions between 2-hydroxy-1,4-naphthoquinone and nitroalkenes [45]. The supported
catalyst 19 could be recycled up to ten times under batch conditions and used
Scheme 7 Reduction of imines with trichlorosilane in a packed-bed flow reactor
37
Reprinted from the journal