Effective Synthesis of a Carbon-linked Diazirinyl Fatty Acid Derivative via Reduction of the Carbonyl Group to Methylene with Triethylsilane and Trifluoroacetic Acid

Friedel-Crafts acylation of the aryldiazirine with ω-ester-α-acyl halide and successive reduction of the carbonyl group to methylene with triethylsilane and trifluoroacetic acid gave diazirinylated fatty acids. Photoaffinity labeling with the carbene generating precursor, 3-phenyl-3-trifluoromethyldiazirine, has become increasingly important as a photophor. However, the complicated synthesis of the diazirinyl ring has resulted in fewer applications of the diazirines in biomolecular studies than other photophors. To resolve the problem, we have previously reported on the post-functional synthesis of a family of 3-phenyl-3-trifluoromethyldiazirines using the Friedel-Crafts reaction as a key step. Synthesis of photoreactive fatty acid analogues presents a similar problem. Carbon-linked diazirinylated fatty acids are synthesized by introducing the fatty acid equivalents before the construction of the diazirinyl ring. 3 To avoid this complication, Friedel-Crafts acylation and successive reduction of carbonyl group to methylene are preferred. However, there is no report on the reduction of carbonyl group to hydrocarbon for diazirinyl compounds. In this paper we describe reduction of carbonyl group in a diazirinylaryl system to methylene with triethylsilane-trifluoroacetic acid and subsequent conversion to the diazirinylated fatty acids.