Topics in Current Chemistry (2019) 377:38
1 3
in high-to-excellent yields and enantioselectivities (up to 96% yield and 99% ee)
(Scheme 27). Furthermore, the scale-up test of the chemical reaction provided the
product 130 in 97% yield and with 98% ee [98]. This was further confirmed by Lu
and collegueas, who reported that desymmetrization of the cyclobutanones 131 proceeded through an enantioselective intramolecular α-arylation, which provided the
structurally interesting compounds 134 found in many bioactive natural products
(Scheme 27). The reaction tolerated both O- and N-tethered aryl bromides, and an
array of substrate scope was demonstrated successfully with a wide range of functionalities [99].
Additionally, the rare transition metal Niobium (Nb) as NbCl 5 have fruitfully
been merged with a primary amine’s enamine activation in the well-known Biginelli reaction [100]. Moreover, the stereoselective reaction presented by Xu and colleagues generates dihydropyrimidiones in moderate to good enantioselectivity (up to
84% ee) and with moderate-to-excellent efficiency (up to 99% yield) [101]. A further
interesting strategy is the integration of oxidation steps in the enamine and transition
metal combined catalysis [102]. In this regard, the group of Luo disclosed the merging of aerobic oxidation and enamine catalysis for the enantioselective synthesis of
R
1
O
R
3
O
R
2
+
O
R
4
NH
O
OH
R
1
O
R
3
O
R
2
N CO 2 R
4
OH
NH 2
N
135
136
1 38
m-nitrobenzoic acid (20 mol%)
CuCl (10 mol%), air, CH 3 CN, r.t.
137 TfOH (20 mol%)
R
1
N
R
3
O
R
2
H
O
R
4
N
O
O
N-selectivity
O
OEt
O
N Cbz
OH
138a 97% yield, 96% ee
O
OMe
O
N Cbz
OH
138b 98% yield, 94% ee
O
OMe
O
N Cbz
OH
138c 81% yield, 88% ee
O
OEt
O
N Cbz
OH
138d 58% yield, >99% ee 138e 58% yield, >99% ee
O
O
OEt
N
OH
Cbz
O
OMe
O
N Cbz
OH
138f 83% yield, 89% ee
XXI
XXII
Scheme 28 Combined transition metal and enamine catalysis integrated with aerobic oxidation
Reprinted from the journal
20
1 3
in high-to-excellent yields and enantioselectivities (up to 96% yield and 99% ee)
(Scheme 27). Furthermore, the scale-up test of the chemical reaction provided the
product 130 in 97% yield and with 98% ee [98]. This was further confirmed by Lu
and collegueas, who reported that desymmetrization of the cyclobutanones 131 proceeded through an enantioselective intramolecular α-arylation, which provided the
structurally interesting compounds 134 found in many bioactive natural products
(Scheme 27). The reaction tolerated both O- and N-tethered aryl bromides, and an
array of substrate scope was demonstrated successfully with a wide range of functionalities [99].
Additionally, the rare transition metal Niobium (Nb) as NbCl 5 have fruitfully
been merged with a primary amine’s enamine activation in the well-known Biginelli reaction [100]. Moreover, the stereoselective reaction presented by Xu and colleagues generates dihydropyrimidiones in moderate to good enantioselectivity (up to
84% ee) and with moderate-to-excellent efficiency (up to 99% yield) [101]. A further
interesting strategy is the integration of oxidation steps in the enamine and transition
metal combined catalysis [102]. In this regard, the group of Luo disclosed the merging of aerobic oxidation and enamine catalysis for the enantioselective synthesis of
R
1
O
R
3
O
R
2
+
O
R
4
NH
O
OH
R
1
O
R
3
O
R
2
N CO 2 R
4
OH
NH 2
N
135
136
1 38
m-nitrobenzoic acid (20 mol%)
CuCl (10 mol%), air, CH 3 CN, r.t.
137 TfOH (20 mol%)
R
1
N
R
3
O
R
2
H
O
R
4
N
O
O
N-selectivity
O
OEt
O
N Cbz
OH
138a 97% yield, 96% ee
O
OMe
O
N Cbz
OH
138b 98% yield, 94% ee
O
OMe
O
N Cbz
OH
138c 81% yield, 88% ee
O
OEt
O
N Cbz
OH
138d 58% yield, >99% ee 138e 58% yield, >99% ee
O
O
OEt
N
OH
Cbz
O
OMe
O
N Cbz
OH
138f 83% yield, 89% ee
XXI
XXII
Scheme 28 Combined transition metal and enamine catalysis integrated with aerobic oxidation
Reprinted from the journal
20