Intramolecular asymmetric C–H insertion of N-arylalkyl, N-bis(trimethylsilyl)methyldiazoamides mediated by chiral rhodium(II) catalysts. Synthesis of (R)-β-benzyl-γ-aminobutyric acid

The enantio- and site-selectivity of the intramolecular C–H insertion reactions of acyclic N-arylalkyl, N-bis(trimethylsilyl)methyl α-diazoacetamides, and α-carboalkoxy-α-diazoacetamides 1a–g, catalyzed by chiral Rh(II) carboxamidates and Rh(II) carboxylates were studied. In general, the reaction showed good to excellent chemoselectivity. Regioselectivity for most of the reactions was high, but was also found to be influenced by the structure of the diazo substrate and the chiral Rh(II) catalyst employed. The highest enantioselectivity for the reactions catalyzed by chiral Rh(II) carboxamidates was 69% and Rh2(4R-MEOX)4 was found to be the most effective. For the chiral Rh(II) carboxylate catalyzed reactions, the highest ee obtained was 75% and Rh2(S-PTTL)4 is the optimal catalyst. The method was applied toward the synthesis of a GABA analogue, (R)-β-benzyl-γ-aminobutyric acid.

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(R)-4-Phenyl-2-pyrrolidinoneC10H11NOEe: 75%[α]D22=-20 (c 0.40, MeOH)Source of chirality: asymmetric C–H insertion catalyzed by Rh2(S-PTTL)4

(S)-4-Phenyl-2-pyrrolidinoneC10H11NOEe: 35%[α]D22=+16 (c 0.63, MeOH)Source of chirality: asymmetric C–H insertion catalyzed by Rh2(4R-MEAZ)4

(S)-4-Benzyl-2-pyrrolidinoneC11H13NOEe: 64%[α]D22=-3.1 (c 0.8, CH2Cl2)Source of chirality: asymmetric C–H insertion catalyzed by Rh2(S-PTTL)4

(R)-1-Benzoyl-4-benzyl-2-pyrrolidinoneC11H19NO[α]D22=-28.6 (c 0.35, CH2Cl2)Source of chirality: asymmetric synthesis

(R)-β-Benzyl-γ-aminobutyric acidC11H15NO2[α]D22=+6.25 (c 1.2, MeOH)Source of chirality: asymmetric synthesis