Design, Synthesis, and Evaluation of a Helicenoidal DMAP Lewis Base Catalyst

Abstract

The design, synthesis, and study of a helical dialkylaminopyridine Lewis base catalyst is reported. Helical DMAP analogue 4 is based upon a helicenoid structure and displays good to excellent levels of selectivity (S ≤ 116) in the kinetic resolution of chiral secondary alcohols. Catalyst 4 displays excellent reactivity with exceptionally low loadings of 0.05 mol % effecting practical levels of selectivity in kinetic resolutions.

Asymmetric addition of chiral boron-ate complexes to cyclic iminium ions

“…The superior levels in terms of efficiency and selectivity prompted us to us to select these reaction conditions for further substrate screening. As revealed in Table 4, this new diastereoselective addition could be adapted to various 60 enantioenriched BACs (4a,b) and dihydroisoquinolones (17,20). In all cases the expected products 19a,b and 21a were formed in good yields and excellent to good diastereoselectivities and complete enantiospecificities (with inversion).…”

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…In comparison to This example clearly demonstrates how the suitably tailor-made design of azahelicenes can provide a useful chiral pyridine-based nucleophilic organocatalyst comparable to other enantiopure amine-containing catalysts, whilst possessing different elements of asymmetry. In comparison to pyridine, dimethylaminopyridine (DMAP) and DMAP-containing compounds 88-90 [61][62][63][64] (Figure 10) are better nucleophilic catalysts for acylation of alcohols due to the enhanced nucleophilicity provided by the electron donating nature of the dimethylamino group at the para position. Thus, (P)-helicenoids 88 containing a p-dialkyl amino substituent turned out to be a more effective enantiodifferentiating catalyst for the resolution of the (S)-enantiomer of racemic 80 with the selectivity factor of 17, in 5 h, as compared to 48 h with a selectivity factor of 7 using (M)-82 as the catalyst.…”

“…Firstly, it enhances the nucleophilicity of the pyridine nitrogen at the 2-position by its electron donating ability (+I effect), and secondly, it increases the conformational flexibility to accommodate reactants inside the helical chiral cavity for efficient enantiodifferentiating processes. The attached ethyl substituents at the central ring of the helical outer core were responsible for increasing the lipophilic character and, thus, the solubility in organic solvents for better performance [61]. The helicenoid DMAP 88 displayed a comparatively higher selectivity factor of 17-116, depending on the structure of the racemic aromatic ethanol.…”

Helicene‐Based Phosphite Ligands in Asymmetric Transition‐Metal Catalysis: Exploring Rh‐Catalyzed Hydroformylation and Ir‐Catalyzed Allylic Amination

“…[22] Recently, Carbery et al developed helicene DMAP Lewis base catalyst 12, which exhibited excellent reactivity as well as selectivity in the kinetic resolution of chiral secondary alcohols (reaching a selectivity factor of up to 116). [23] Thus, to the best of our knowledge, there are no other examples of true helicene-based ligands that are used in asymmetric transition-metal catalysis or organocatalysis. In addition to the helical ligands discussed so far, newly emerging family of monodentate phosphites 13, phosphinites 14, and phosphoramidites 15 ( Figure 2) derived from BINOL can definitely not be neglected.…”