Synthesis of a Novel Chiral Cubane-Based Schiff Base Ligand and Its Application in Asymmetric Nitro-Aldol (Henry) Reactions

Abstract

The first reported cubane-based chiral Schiff base ligand has been successfully synthesized. This ligand has been evaluated on the nitro-aldol (Henry) reaction. The reactions were performed in the presence of four different copper salts, using eight different solvents, and five different temperatures. The highest enantioselectivity obtained for this novel ligand was ~39% ee.

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

“…With both CH 2 Cl 2 and THF the ee values significantly dropped (Table 2, entry 2 and 3). As previously reported, CuCl gave the best results with the Henry reaction [19]; hence, we decided to evaluate this copper source. This, however, did not yield any encouraging results with only a maximum ee value of 4% when performed in Et 2 O (Table 2, entry 4).…”

“…1) and screened it in the Henry reaction in the synthesis of β-nitroalcohols [19]. The cubyl moiety can be considered a cross between a tert -butyl and a phenyl group.…”

Cubane: 50 Years Later

“…The chiral cubane containing Schiff base ligand 220 was developed in 2010 and was applied to an asymmetric Henry reaction. 185 The ligand was able to provided high conversions and moderate enatioselectivity (up to 39% ee).…”

“…1,2,3,5,7-Pentanitrocubane (184) was found to be colorless and highly crystalline, showing no obvious shock sensitivity or special thermal sensitivity, with decomposition occurring only above 250°C. 150 When the bis(triethyllead) derivative (185) was treated with N 2 O 4 , followed by ozonolysis, a 40% isolated yield of a 40:60 mixture of pentanitrocubane (184) with hexanitrocubane (186) was obtained (Scheme 49). 150 The relative acidity of tetranitrocubane (170) proved to be the key to preparing the higher nitrocubane compounds.…”

“…Another novel use of cubane in recent years has focused on using it in catalysis, specifically incorporation of the cubane scaffold into a chiral ligand. The chiral cubane containing Schiff base ligand 220 was developed in 2010 and was applied to an asymmetric Henry reaction . The ligand was able to provided high conversions and moderate enatioselectivity (up to 39% ee ).…”