One‐Pot Enantioselective Synthesis of 3‐Nitro‐2H‐chromenes Catalyzed by a Simple 4‐Hydroxyprolinamide with 4‐Nitrophenol as Cocatalyst

Abstract

The asymmetric domino oxa‐Michael–Henry reaction of salicylaldehyde derivatives with trans‐β‐nitro olefins catalyzed by a readily available trans‐4‐hydroxy‐L‐prolinamide with 4‐nitrophenol as an effective cocatalyst is presented. The corresponding 3‐nitro‐2H‐chromenes were obtained in moderate to excellent yields (up to 99 %) and with up to 90 % ee under mild conditions. In addition, a preliminary study shows that this organocatalytic system is able to promote the domino aza‐Michael–Henry reaction of 2‐formylpyrrole derivatives with trans‐β‐nitro olefins to give chiral 2‐nitro‐3H‐pyrrolizines.

Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4-addition/Michael reaction through dynamic kinetic resolution under iminium catalysis. Development and mechanistic insights

“…Consequently, the reported examples of organocatalytic and enantioselective conjugate addition of oxygen pronucleophiles are limited to the use of oximes, 7 phenols, 8 enols, 9 alkoxyboronates, 10 hydroxylamines, 11 or peroxides 12 under iminium or H-bonding activation. 13 Organocatalytic cascade processes initiated by conjugate addition of O -nucleophiles have been mainly focused on the epoxidation of α,β-unsaturated carbonyls with peroxides 14 and some limited examples of conjugate addition followed by aldol, 15 Mannich, 16 Henry, 17 α-amination 18 and α-fluorination 19 have also been published. However, with respect to 1,4-addition/Michael cascade processes, all cases reported are strictly limited to the use of aliphatic alcohols or phenols as oxygen-centered pronucleophiles (Scheme 1).…”

Heterogeneous Synergistic Catalysis for Promoting Aza-Michael–Henry Tandem Reaction for the Synthesis of Chiral 3-Nitro-1,2-Dihydroquinoline

“…It is found that SBA-15-Q and SBA-15-AEP possessing tertiary amine structure promote the asymmetric cascade reaction more efficiently than SBA-15-PY with individual secondary amine. Based on the above analysis and the previous reports [49][50][51], the heterogeneous mechanism for SBA-15 immobilized secondary amine ( Figure 2) and tertiary amine ( Figure 3) has been proposed respectively. For SBA-15-PY ( Figure 2), firstly in the aza-Michael reaction, secondary amine reacts as a nucleophile with the carbonyl group of 2-aminobenzaldehyde to form iminium ions giving H 2 O [52].…”

“…For SBA-15-PY ( Figure 2), firstly in the aza-Michael reaction, secondary amine reacts as a nucleophile with the carbonyl group of 2-aminobenzaldehyde to form iminium ions giving H 2 O [52]. β-nitrostyrolene is activated by the surface silanols as hydrogen-bonding donor, which is helpful to connect the electrophile to the iminium-activated 2-aminobenzaldehyde in the transition state [49]. Then the N of amino group in the iminium intermediate nucleophilically attacks the α-C in the activated β-nitrostyrolene and abstracts H from amino-group to form the stereoselectivity.…”

Facile access to 2-aryl-3-nitro-2H-chromenes and 2,3,4-trisubstituted chromanes

“…-3-nitro-2-phenyl-2H-chromene (3e). 12,29 R f (n-hexane/EtOAc 50:1): 0.50; yellow crystals, mp 143-145 °C (Lit. 140-141 °C for racemic, 147 °C for R-form).…”

“…Several reports describe construction of 2-aryl-3-nitro-2H-chromenes in good yields using 1,4-diazabicyclo[2.2.2]octane (DABCO), 7,8 L-pipecolinic acid 9 or C 2 -symmetric pyrrolidine-triazoles 10 as catalysts. The preparation of optically active 2-aryl-3-nitro-2H-chromenes through asymmetric tandem oxaMichael-Henry reactions has also been realized recently, with chiral pyrrolidine derivatives, 11,12 or cinchona alkaloid-derived bifunctional thioureas 13 as catalysts under mild conditions, respectively. Kinetic resolution of racemic 2-aryl-3-nitro-2H-chromenes can also be used to provide their enantioriched forms.…”