Development and Applications of Disulfonimides in Enantioselective Organocatalysis

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

“…Conversely, and as expected, addition of silver compounds such as AgOTs led to significantly lower ee due to competition from the racemic reaction catalysed by in situ generated strong acid (TsOH; entry 7). We next screened different combinations of various BINOL (1,1′-bi-2-naphthol)- and SPINOL (2,2′,3,3′-tetrahydro-1,1′-spirobi[indene]-7,7′-diol) CPAs4344454647 and Cu salts (entries 6 and 8–18) and found that the dual catalyst composed of CuBr (10 mol%) and ( S )- 1A (5 mol%) with 4-Ph-phenyl group at the 3,3′-positions was the best in terms of enantioselectivity (90% ee; entry 6). Among the solvents screened (entries 19–23), ethyl isobutyrate was found to be the most efficient one (98% yield and 99% ee; entry 23).…”

Lewis acid enhancement by hydrogen-bond donors for asymmetric catalysis

“…The reactivity of these reagents is enhanced through incorporation of more weakly coordinating anionic ligands such as disulfonimides, as demonstrated initially by Ghosez in racemic Diels-Alder reactions (7,8,9). List and coworkers extended this advance to enantioselective catalysis through the design of chiral disulfonimide counteranion that associate with the active silylium species (10, 11). We envisaged an alternative approach wherein association of a chiral H-bond donor with the triflate anion would generate a charge-separated complex with enhanced Lewis acidity relative to silyl triflate alone.…”

One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence

“…Over the past decade, asymmetric organic catalysis [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], quite powerful for synthesizing various heterocyclic molecules, has formed the basis of several elegant approaches to construct chiral single-heterocycle piperidine skeletons with high efficiency and low toxicity under environmentally friendly conditions . In contrast, relatively few organocatalytic methods have been described to stereo-selectively form spirocyclic piperidine derivatives [30][31][32][33][34][35][36], particularly ones with a quaternary stereocenter [37][38][39].…”

“…Strong electron-withdrawing aryl groups on enal 3 (entries 8-9) gave slightly higher 91 yields and stereoselectivities than electron-donating aryl groups (entries [10][11][12] Using these optimized conditions (Table 1, entry 12), we explored the scope and limitations of this method using α,β-unsaturated aldehyde 3, cyclic 2-diazo-1,3-diketone 1 and primary amine 2 (Table 2). Generally, the reaction was flexible in affording the desired spirocyclic piperidones.…”

“…Halogen substitutions such as -F, -Cl, and -Br at the meta or para positions of aryl groups in enal 3 (entries 2-5) gave better yields and stereoselectivities than such substitutions at the ortho position (entries 6 and 7). Strong electron-withdrawing aryl groups on enal 3 (entries 8 and 9) gave slightly higher yields and stereoselectivities than electron-donating aryl groups (entries [10][11][12]. The heteroaromatic group furan led to the desired product 5m with high ee and good dr value (entry 13).…”