Double axially chiral bisphosphorylimides as novel Brønsted acids in asymmetric three-component Mannich reaction

A double axially chiral bisphosphorylimide has been demonstrated to be an efficient and highly sterically hindered Brønsted acid in asymmetric three-component Mannich reactions. Optically active syn-β-amino ketones were obtained in high yields (up to 99%) with excellent diastereoselectivity (99:1) and enantioselectivity (up to 99% ee). A gram-scale reaction was also performed to prove the synthetic application value of this reaction.

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(11b′R)-4,4′-Azanediylbis(dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepine 4-oxide)C40H25NO6P2[α]D20=-99.6 (c 1, THF)Source of chirality: (R)-(+)-1,1′-bi-2-naphtholAbsolute configuration: (R,R)

(11b′R)-4,4′-Azanediylbis(2,6-diphenyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepine 4-oxide)C64H41NO6P2[α]D20=-175.6 (c 1, THF)Source of chirality: (R)-(+)-1,1′-bi-2-naphtholAbsolute configuration: (R,R)

4-(((11bR)-2,6-Di(naphthalen-1-yl)-4-oxidodinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)amino)-2,6-diphenyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepine 4-oxideC72H45NO6P2[α]D20=-204.6 (c 1, THF)Source of chirality: (R)-(+)-1,1′-bi-2-naphtholAbsolute configuration: (R,R)

(11b′R)-4,4′-Azanediylbis(2,6-di(naphthalen-1-yl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepine 4-oxide)C80H49NO6P2[α]D20=-94.2 (c 1, THF)Source of chirality: (R)-(+)-1,1′-bi-2-naphtholAbsolute configuration: (R,R)

4-(((11bR)-2,6-Bis(3,5-bis(trifluoromethyl)phenyl)-4-oxidodinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)amino)-2,6-diphenyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepine 4-oxideC68H37F12NO6P2[α]D20=-307.0 (c 1, THF)Source of chirality: (R)-(+)-1,1′-bi-2-naphtholAbsolute configuration: (R,R)

4-(((11bR)-2,6-Bis(3,5-dimethylphenyl)-4-oxidodinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)amino)-2,6-diphenyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepine 4-oxideC68H49NO6P2[α]D20=-258.0 (c 1, THF)Source of chirality: (R)-(+)-1,1′-bi-2-naphtholAbsolute configuration: (R,R)