BINOL-based azacrown ether catalyzed enantioselective Michael addition: asymmetric synthesis of α-aminophosphonates

Several novel 1,1′-bi-2-naphthyl-appended azacrown ethers with donor side-arms were synthesized and applied for the first time as chiral catalysts in the asymmetric Michael addition of an N-protected aminomethylenephosphonate onto acrylonitriles, resulting in high diastereoselectivity and enantioselectivity. The absolute configuration of the adduct was determined from its experimental and calculated CD spectra.

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(R)-13-(3-Butyl)-8,9,12,13,14,15,17,18-octahydro-11H-dinaphtho[1,2-p:1,2-n] [1,4,10,13,7]tetraoxaazacycloheptadecineC32H37NO4[α]D22=+127.4 (c 0.95, CHCl3).Source of chirality: (R)-1,1′-bi-naphth-2-olAbsolute configuration: (1R,1′R)

(R)-13-(3-Hyroxypropyl)-8,9,12,13,14,15,17,18-octahydro-11H-dinaphtho[1,2-p:1,2-n] [1,4,10,13,7]tetraoxaazacycloheptadecineC31H35NO5[α]D22=+171 (c 0.76, CHCl3)Source of chirality: (R)-1,1′-bi-naphth-2-olAbsolute configuration: (1R,1′R)

(R)-13-(3-Methoxypropyl)-8,9,12,13,14,15,17,18-octahydro-11H-dinaphtho[1,2-p:1,2-n] [1,4,10,13,7]tetraoxaazacycloheptadecineC32H37NO5[α]D22=+140 (c 1.5, CHCl3)Source of chirality: (R)-1,1′-bi-naphth-2-olAbsolute configuration: (1R,1′R)

(R)-13-[2-(2-Methoxyphenyl)ethyl]-8,9,12,13,14,15,17,18-octahydro-11H-dinaphtho[1,2-p:1,2-n] [1,4,10,13,7]tetraoxazacycloheptadecineC37H39NO5[α]D22=+118 (c 2, CHCl3)Source of chirality: (R)-1,1′-bi-naphth-2-olAbsolute configuration: (1R, 1′R)

(R)-13-[2-(3-Methoxyphenyl)ethyl]-8,9,12,13,14,15,17,18octahydro-11H-dinaphtho[1,2-p:1,2-n][1,4,10,13,7] tetraoxazacycloheptadecineC37H39NO5[α]D22=+154 (c 0.94, CHCl3)Source of chirality: (R)-1,1′-bi-naphth-2-olAbsolute configuration: (1R, 1′R)

(R)-13-[2-(4-Methoxyphenyl)ethyl]-8,9,12,13,14,15,17,18octahydro-11H-dinaphtho[1,2-p:1,2-n][1,4,10,13,7]tetraoxazacycloheptadecineC37H39NO5[α]D22=+100 (c 1.6, CHCl3)Source of chirality: (R)-1,1′-bi-naphth-2-olAbsolute configuration: (1R, 1′R)

(R)-13-[2-(3,4-Dimethoxyphenyl)ethyl]-8,9,12,13,14,15,17,18-octahydro-11H-dinaphtho[1,2-p:1,2-n] [1,4,10,13,7]tetraoxazacycloheptadecineC38H41NO6[α]D22=+120 (c 1.1, CHCl3)Source of chirality: R-1,1′-bi-naphth-2-olAbsolute configuration: 1R, 1′R

[1S-(Benzhydrylidene-amino)-3R-cyano-3-methyl-propyl]-phosphonic acid diethyl esterC22H27N2O3P[α]D22=+17.1 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 1S,3R