Enantio- and periselective nitroalkene Diels–Alder reaction

Abstract

The periselective Diels-Alder reaction of 5-substituted pentamethylcyclopentadienes and nitroethylene has been realized by helical-chiral hydrogen bond donor catalysts. To our knowledge, this represents the first asymmetric catalytic nitroalkene Diels-Alder reaction via activation of nitroalkene, and thus establishes its proof-of-principle.

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…Another example of the activation of nitroalkenes via the hydrogen bonding donor characteristics was demonstrated by using aminopyridinium-based (M)- [6]helicene 108 in the asymmetric Diels-Alder reaction between cyclopentadienes 109 and nitroethylene 110 to give the cycloadduct product 111 in moderate 30-40% ee [71]. A traditional hydrogen bonded catalyst generally requires the complementary donor-acceptor units in both reactants to orient specifically for asymmetric induction in the addition reaction.…”

Enantio- and Periselective Nitroalkene Diels-Alder Reactions Catalyzed by Helical-Chiral Hydrogen Bond Donor Catalysts

“…As part of our broad interest in helicene-derived catalysts, we have recently developed double hydrogen bond donor catalysts based on 1-azahelicene, which do not require additional complementary functionalities for asymmetric induction (Figure 1) [33]. In order to pursue the possibility of catalyzing the nitroalkene Diels-Alder reaction by these type of catalysts, we chose cyclopentadiene 2 as a model substrate because 5-substituted pentamethylcyclopentadienes are readily available [34,35] and are similar to the desired 1,4,5,5-tetrasubstituted cyclopentadienes ( 1 ) in terms of their structures (Table 1). To our delight, catalyst 4 indeed catalyzed the nitroalkene Diels-Alder reaction, providing only the desired product ( i.e ., no inverse electron-demand hetero Diels-Alder product) with definite enantioselectivity (entry 2).…”

Applications of Helical‐Chiral Pyridines as Organocatalysts in Asymmetric Synthesis

“…An aliphatic nitroalkene also provided good enantioselectivities ( Table 2, entries 12 and 16). Several substituted 4,7-dihydroindoles and a pyrrole were evaluated next and were also found to be good substrates for this reaction ( Table 2, entries [13][14][15][16][17]. Whilst catalyst 10a was found to be equally effective in the initial experiments with both 4,7-dihydroindole and indole ( Table 1, entry 1 and Table 2, entry 18), to our surprise, the catalyst that was optimized for 4,7-dihydroindoles (7e) turned out to be virtually un-reactive for an indole nucleophile ( Table 2, entry 19).…”

“…2) 1-Azahelicenes are effective chiral scaffolds for the construction of catalyst structures that are otherwise difficult to access. [16] Asymmetric LUMO-lowering catalysis is one of the mostextensively studied procedures for the Diels-Alder reaction and its current state is certainly impressive. [17] However, suitable dienophiles are limited to carbonyl compounds, which leaves a tremendous gap in an otherwise-robust field of chemistry.…”