Preparation of chiral 1,2,4-triazolium salts as new NHC precatalysts

The preparation of new chiral N,N′-disubstituted 1,2,4-triazolium based NHC salt precursors, Ia′ and Ib, from phenylhydrazine and l-phenylalanine is reported. The 1,3,4-trisubstituted triazolium salt Ia′ was obtained by a stepwise ring construction from l-phenylalanine via the corresponding imino ether and acetohydrazonamide, while a heterocyclic O-/N-heteroatom exchange strategy, based on a ring-opening/ring-closure of the oxadiazolium precursor, afforded the 1,4-disubstituted 1,2,4-triazolium salt Ib. The need for two different synthetic strategies is discussed.

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(S)-N-(1-(Benzyloxy)-3-phenylpropan-2-yl)acetamideC18H21NO2[α]D20=-16.3 (c 0.71, MeOH)Source of chirality: l-phenylalanineAbsolute configuration: (2S)

(S)-Methyl N-1-(benzyloxy)-3-phenylpropan-2-ylacetimidateC19H23NO2[α]D20=-65.3 (c 0.89, MeOH)Source of chirality: l-phenylalanineAbsolute configuration: (2S)

(S)-4-(1-(Benzyloxy)-3-phenylpropan-2-yl)-3-methyl-1-phenyl-4H-1,2,4-triazol-1-ium chlorideC25H26N3OCl[α]D20=-23.0 (c 0.99, MeOH)Source of chirality: l-phenylalanineAbsolute configuration: (2′S)

(S)-4-(1-(Benzyloxy)-3-phenylpropan-2-yl)-3-methyl-1-phenyl-4H-1,2,4-triazol-1-iumperchlorateC25H26N3OClO4[α]D20=-63.8 (c 1.08, MeOH)Source of chirality: l-phenylalanineAbsolute configuration: (2′S)

(S)-4-(1-(Benzyloxy)-3-phenylpropan-2-yl)-1-phenyl-4H-1,2,4-triazol-1-ium per chlorateC24H24N3OClO4[α]D20=-41.4 (c 1.01, MeOH)Source of chirality: l-phenylalanineAbsolute configuration: (2′S)

(S)-1-Phenyl-4-(1-phenylethyl)-4H-1,2,4-triazol-1-ium perchlorateC16H16N3ClO4[α]D20=+25.2 (c 1.03, MeOH)Source of chirality: (S)-1-phenylethanamineAbsolute configuration: (1′S)