New Simple Polymeric Supports with Hydrazone Linkers for Solid-Phase Synthesis of Ketones and Primary Amines

Abstract

The preparation of new solid supports with hydrazine anchoring groups and their application to solid-phase synthesis of ketones and primary amines are described. The supports were used for immobilization of ketones, 4-tert-butylcyclohexanone, pentan-3-one, acetone, N-methylpiperidone, N-benzylpiperidone, and tropinone in the form of their hydrazones. The polymer-supported hydrazones were subjected to deprotonation/alkylation procedure (LDA/RX) once or twice. The resulting alkylated products were cleaved off the solid support on treatment with trifluoroacetic acid in tetrahydrofuran providing α-alkylated or α,α′-bisalkylated ketones or were subjected to reductive cleavage with borane in tetrahydrofuran to give β-alkylated or β,β′-bisalkylated primary amines.

Key words

alkylations - hydrazones - ketones - amines - solid-phase synthesis

References

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10

CAUTION! N-Nitrosoamines are potentially carcinogenic. Therefore we recommend special caution during handling and preparation.

11

Microanalytical data (% of N) did not always show accurately the loading of hydrazine or hydrazone on the resins. Therefore a method based on gravimetric measurement was used. [4]

12

The typical condition [4] for cleavage of hydrazone linker with TFA-CH₂Cl₂ gave incomplete cleavage. The cleavage was satisfactory with TFA in wet THF.