Synthesis of hindered secondary amines via Grignard reagent addition to ketonitrones

✍ Scribed by Martin A. Schwartz; Xiufeng Hu

• Book ID: 104224775
• Publisher: Elsevier Science
• Year: 1992
• Tongue: French
• Weight: 323 KB
• Volume: 33
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)91707-6

✦ Synopsis

Grignard reagents add to ketonirrones in a nonpolar solvent to afford N,N-dialkylhydroxylamines in good yieids and with liiule compeling proton Paqfer.

Deoxygenalion of the crude hydroxylatrSnes with carbon disulfide then compleres an eficient general synthetic route to hindered set-alkyl-lert-alkylnmines and to di-terl-olkylamines.

We recently described a new synthetic route to 1-substituted-1,4-dihydro-3(2H)-isoquinolinones and related compounds that required N-a-aralkyl-N-tert-butyl-substituted secondary amines as starting materials.1*2 While many of the latter amines proved to be readily available by reductive amination of ketones3-5 with tertbutylamine, that method gave very poor results in our hands (8-13% yields) when applied to the preparation of secondary amines such as 1 from the corresponding a-tetralones (Scheme 1). 2 Secondary N-sec-alkyl-N-tert-