Synthesis and reactions of sulfinimines

• Main Author: Sasraku-Neequaye, Leonid Kotei
• Published: University of East Anglia 2010
• Subjects: 547
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569322

A large majority of drugs and drug candidates incorporate amine functionality and these include important compounds such as morphine, quinine and nicotine. N-Sulfinyl-imines (sulfinimines) are a versatile class of intermediates in organic synthesis particularly for the preparation of amines and amine derivatives. We herein report an efficient and cost effective one-pot synthesis of sulfinimines in enantiopure form (>99.8% ee) and in relatively high yields. In our investigations, we developed the scheme that involves the use of 1,2,3-oxathiazolidine-2-oxide derived from (1R, 2S)-(-)-norephedrine as a chiral auxiliary. Opening of the 1,2,3-oxathiazolidine-2-oxide with a mesityl Grignard reagent followed by treatment of the crude mixture with lithium hexamethyldisilasane afforded the mestyl sulfinamide in 72% yield and 76% recovery of the chiral auxiliary. As an extension to this scheme, when the crude reaction mixture obtained after addition of the lithium hexamethyldisilasane was treated with 1.1 equivalents of an aldehyde and three (3) equivalents of Ti(OEt)4 afforded the corresponding mesityl sulfinimines in high yields (>30 – 60%) and excellent enantiomeric excess (>99.8%). This to our knowledge is the first ever 3-step, one-pot syntheses of enantiopure sulfinimines using chiral aminoalcohol derived 1,2,3-oxathiazolidine-2-oxide as a chiral auxiliary. The mesitylsulfinamide thus produced was utilised in a novel free radical cyclisation reaction to yield mesitylsulfinyl protected enantiopure aminoindane in 68% yield.