Highly Concise Synthesis of 3'‐"Up"‐ethynyl‐5'‐methylbicyclo‐ [3.1.0]hexyl Purine and Pyrimidine Nucleoside Derivatives Using Rhodium(II) Carbenoid Cycloaddition and Highly Diastereoselective Grignard Reaction

Synthesis of north ‐5'‐methylbicyclo[3.1.0]hexyl purine and pyrimidine nucleosides with an ethynyl group at C‐3' position has been successfully accomplished by a facile method. Methylbicyclo[3.1.0]hexanone (±)‐ 5 having three contiguous chiral centers was remarkably simply constructed only by four steps containing a carbenoid insertion reaction in the presence of rhodium(II) acetate dimer and CuSO 4 , giving a correct relative stereochemistry of the generated three chiral centers. Upon Grignard reaction of (±)‐ 5 with ethynylmagnesium bromide, exclusive diastereoselectivity was observed. Condensation of glycosyl donor (±)‐ 9 with purine nucleobase afforded only the desired N 9 ‐alkylated nucleoside, while condensation with pyrimidine, N 3 ‐benzoylated uracil gave the desired N 1 ‐alkylated nucleoside (±)‐ 13 with the undesired O 2 ‐alkylated nucleoside (±)‐ 14 . Probably, (±)‐ 14 would be formed due to steric hindrance caused upon approaching for N 1 ‐alkylation.