Synthesis and Catalytic Activity of Organocatalysts Based on Enaminone and Benzenediamine Hydrogen Bond Donors

Abstract

A total of 24 novel organocatalysts based on (S)-quininamine as a chiral tertiary amine and on enaminone or 1,2-benzenediamine as hydrogen bond donors were synthesized. The enaminone-type catalysts were prepared by the transamination of N,N-dimethyl enaminones with (S)-quininamine (9 examples) and the 1,2-benzenediamine-type catalysts were prepared in 3 steps from (S)-quininamine and ortho-fluoronitrobenzene derivatives (15 examples). Their organocatalytic activity was evaluated in the Michael addition of acetylacetone to trans-β-nitrostyrene. Enantioselectivities of up to 72% ee were observed.

Synthesis and Catalytic Activity of 1,2-Benzenediamine-Derived Organocatalysts Based on (1R,2R)-Cyclohexane-1,2-diamine

“…Only unsubstituted ortho-fluoronitrobenzene (2a) and ortho-fluoronitrobenzene derivatives 2b-e substituted with electron withdrawing groups (CF3, CN) were considered. The electron-donating substituents have a detrimental effect on enantioselectivity and yield, as has already been shown [27].Subsequently, the primary aliphatic amino group of 3 was selectively alkylated. To introduce the dimethylamino group for the preparation of compounds 4, reductive alkylation with aqueous formaldehyde using NaCNBH3 in acetonitrile worked best (4 prepared in 68-99% yields), since alkylation with iodomethane was accompanied by numerous side products.…”

“…All reactions were carried out in anhydrous dichloromethane at 25°C for 24 hours with 10 mol% of the catalyst (Table 1). Similar to the quinuclidine-derived analogues [27], all the synthesized subtypes of organocatalysts were characterized by incomplete conversion (up to 93%) and low (S)-enantioselectivity (up to 41% ee). For comparison, the squaramide organocatalyst 21 [40] yielded the addition product C in 98% conversion and with high reversed enantioselectivity (93% ee, R) (Table 1, Entry 1).…”

“…First, a reliable and as straightforward as possible synthesis of the chiral benzene-1,2-diamine building blocks 6 and 7, which contain a primary aromatic amino group and an aliphatic tertiary amino group, had to be established starting from inexpensive, commercially available (1R,2R)cyclohexane-1,2-diamine and ortho-fluoronitrobenzene derivatives (Scheme 1). While the introduction of the benzene-1,2-diamine moiety was already developed on a chiral (S)-quininamine scaffold [27], the introduction of the aliphatic tertiary amino group had to be considered. Although the initial introduction of the tertiary amino group is well documented in the literature [32][33][34][35], this would potentially introduce unwanted additional protection/deprotection steps.…”

“…Their catalytic activity was evaluated in the Michael addition of acetylacetone to trans-β-nitrostyrene. The catalysts were characterized by low to moderate enantioselectivity (up to 72% ee) at low conversions (up to 41%) [27]. Furthermore, no N-arylated (3,5bis(trifluoromethyl)phenyl) and N-benzylated (3,5-bis(trifluoromethyl)benzyl) catalysts could be prepared.…”

Synthesis of N1-(3,5-Bis(trifluoromethyl)benzyl)benzene-1,2-diamine and N,N-Bis(2-nitrophenyl)-3,5-bis(trifluoromethyl)aniline

“…1,2-Disubstituted benzimidazoles based on substituted diaminobenzenes have been tested for their cytotoxicity against cancer cells [6,7]. Benzene-1,2-diamine derivatives have been tested as donors for double hydrogen bond donors in non-covalent organocatalysts [8]. Triphenylamine-based diamines are important and versatile monomers for the synthesis of aromatic polyamides with different properties [9][10][11][12][13][14][15].…”