Iodocyclofunctionalization of (E)-1-trichloroacetimidoalk-2-enes. Synthesis of (±)-erythro-sphinganine triacetate

Abstract

From the iodocyclization of (E)-1-trichloroacetimido-octadec-2-ene, 5-iodo-4-pentadecyl-2-trichloromethyl-5,6-dihydro-4H-oxazine was unexpectedly obtained, whose structure was assigned from i.r. and ¹H n.m.r. spectra. The stereostructure of this oxazine was further confirmed by chemical evidence: thus, the compound was hydrolysed on silica gel to give 2-iodo-3-trichloroacetamido-octadecan-1-ol, and successive treatment with Amberlyst A 26 (CO₃^2– form) yielded cis-5-hydroxymethyl-4-pentadecyl-4,5-dihydrooxazole, whose configuration was determined by ¹H n.m.r. data. Acidic hydrolysis of this oxazole and acetylation led to erythro-3-amino-octadecane-1,2-diol triacetate. To ascertain definitively the structure of this triacetate, 3-trichloroacetamido-octadec-1-ene was cyclized, to yield 5-iodomethyl-4-pentadecyl-4,5-dihydrooxazole as a 45:55 cis : trans mixture. After hydrolysis of the cis-isomer, treatment with Amberlyst A 26 (AcO^– form), and full acetylation, the aforementioned erythro-triacetate was obtained.

Confirming the unequivocal assignment of the stereostructure of 5-iodo-4-pentadecyl-2-trichloro-methyl-5,6-dihydro-4H-oxazine, its acidic cleavage gave 3-amino-1-iodo-octadecan-2-ol hydrochloride. By treatment of this salt with Amberlyst A 26 (AcO^– form), full acetylation of the product afforded (±)-erythro-sphinganine triacetate in good yield, contaminated with a minor amount of the regioisomeric 3-amino-octadecanediol triacetate.