Naplephos: a modular library of chiral phosphines based on d-glucose for highly enantioselective asymmetric catalysis

Simple functionalisation of N-acetylglucosamine produces the modular ligand library naplephos, which combines the performance of ‘privileged’ ligands based on 1,2-trans-cyclohexanediamine with flexibility and accessibility. With the proper choice of substituents, the basic structure was suitably adapted to the Pd-catalysed asymmetric allylic alkylation of rac-(E)-1,3-diphenyl-2-propenyl acetate with dimethyl malonate, producing the (S)-product in ee’s of up to 96% ee.

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Naplephos-bC42H40NO8P[α]D = −7.9 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-cC48H44NO8P[α]D = +7.8 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-dC48H50NO8P[α]D = +20.8 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-eC45H46NO8P[α]D = -2.2 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-fC50H48NO8P[α]D = -16.6 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-gC50H48NO8P[α]D = +41.1 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-hC54H48NO8P[α]D = −23.0 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-iC55H50NO8P[α]D = −28.6 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-jC54H60NO8P[α]D = +14.5 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-kC47H42NO8P[α]D = -2.0 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

Naplephos-lC48H39F5NO8P[α]D = +12.7 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

C40H38NO7P[α]D = +6.7 (c 1, CHCl3)Source of chirality: N-acetyl-d-glucosamineAbsolute configuration: (1S,2R,3R,4S,5R)

C39H36NO3P[α]D = -59.4 (c 1, CHCl3)Source of chirality: (1S,2S)-2-aminocyclohexanolAbsolute configuration: (1S,2S)