Morita–Baylis–Hillman Reactions with Nitroalkenes: A Case Study

Abstract

We report on the use of a highly reactive super‐DMAP catalyst in Morita–Baylis–Hillman (MBH) reactions of nitroalkenes with ethyl glyoxylate, which result in excellent conversions and short reaction times with, importantly, very low catalyst loading. An extensive study of this particular reaction is presented, which examines all mechanistic and experimental details. Several critical points were hence uncovered that include the correlation between reaction efficiency and Lewis basicity of the catalyst; the double role played by the promoter, primarily as a nucleophilic activator towards the nitroalkene, and as a Brønsted base that triggers glyoxylate depolymerisation. More generally, the limitations in the choice of electrophiles that can engage efficiently in MBH‐type transformations are rationalized by the competition between a productive pathway and a nitroalkene polymerization process. Other aspects of this transformation, used as a case study, are presented in the light of physical organic chemistry.

Unprecedented Mechanism of an Organocatalytic Route to Conjugated Enynes with a Junction to Cyclic Nitronates

“…[27,49] This polymerization was evident from mass spectrometry (electrospray ionisation) throughout a one-pot reaction of 1a with DBU revealing molecular ion peaks with m/z ratios higher than 800 (see Table 3 in SI). [27,49] This polymerization was evident from mass spectrometry (electrospray ionisation) throughout a one-pot reaction of 1a with DBU revealing molecular ion peaks with m/z ratios higher than 800 (see Table 3 in SI).…”

“…[41,42] While the buildup of N 2 was detected (see above) as comproportionation product of HNO and H 2 NOH, a degradation of HNO to N 2 O [45,46] (see Scheme 3e in SI) was not observed in the NMR kinetic measurements of 1a 15 N ( 15 N 2 O signals should appear at around 155 ppm and 240 ppm). [49] Next, the effects of different acids, substituents and bases were investigated to get further insights into the mechanism of the conjugated enyne formation. A carboxylic acid as additive accelerated significantly the formation of enyne and suppressed the formation of nitronate almost completely (compare a and b).…”

α-Functionalization of Nitroalkenes and Its Applications in Organic Synthesis

“…In addition, they performed the comparative study of electrophilicity of electrophiles and nitroalkenes responsible for the undesired polymerization during these reactions (Scheme 4). 23 For instance, they found that super-DMAP (17) (s-DMAP) was the best catalyst for this reaction.…”

Spectroscopic Identifications, Molecular Docking, Neuronal Growth and Enzyme Inhibitory Activities of Steroidal Nitro Olefin: Quantum Chemical Study

“…Nitro olefins including cyclic nitro olefins are resourceful intermediates in synthetic organic chemistry as well as in the chemical industry. They are also applied in various constructions of carbon–carbon bonds, such as the Michael reaction, Diels–Alder cycloaddition and Morita–Baylis–Hillman reaction . Besides, it is easy to transform the nitro group into other useful functional groups, for example, nitro compounds provide access to valuable synthetic precursors namely nitroalkanes, N‐substituted hydroxylamines, amines, ketones, oximes, α‐substituted oximes and α‐substituted ketones .…”

“…They are also applied in various constructions of carbon-carbon bonds, such as the Michael reaction, Diels-Alder cycloaddition and Morita-Baylis-Hillman reaction. [14][15][16] Besides, it is easy to transform the nitro group into other useful functional groups, for example, nitro compounds provide access to valuable synthetic precursors namely nitroalkanes, N-substituted hydroxylamines, amines, ketones, oximes, α-substituted oximes and α-substituted ketones. [17][18][19][20] Nitro olefins have extensive application in materials, pharmaceuticals, agrochemicals and so on.…”