Cyclopropanation is regarded as an important transformation in organic synthesis. [1] Synthesis of 3-azabicyclo-A C H T U N G T R E N N U N G [3.1.0]hexane structures has been of interest because compounds with these structures, for example, indolizomycin, [2] trovafloxacin, [3] duocarmycin, and CC-1065 [4] show significant biological activity. Preparation of these structures involves low-valent titanium-mediated cyclization (the Kulinkovich reaction), which has recently been explored extensively by de Meijere and others. [5, 6] Another method using cyclopropyllithium reagents has also been reported. [7] Aliphatic nitro compounds are recognized as useful synthetic building blocks because the nitro group has a strong electron-withdrawing property. [8] The a-anions of the nitro compounds are easily oxidized to the corresponding carbon radicals by treatment with ceric ammonium nitrate, silver(I) salts, K 3 Fe(CN) 6 , and MnA C H T U N G T R E N N U N G (OAc) 3 . [9] These radicals are frequently used to form new carbonÀcarbon bonds [10] through radical cyclization. [11] However, to the best of our knowledge, there are currently no successful studies reported to show a direct cyclopropanation process using primary nitro compounds. In this paper, we report a novel intramolecular cyclopropanation from b-nitroamides or b-nitroethers through a higher-order domino reaction to give bicyclic nitrocyclopropanes in a stereoselective manner.
Preparation of the cyclization precursors 1, 2 and 3 was carried out by the conjugate addition of formamides, alkoxides, and thiolate to nitroalkenes. [12] Treatment of 1 a with Ag 2 O and iodine in the presence of DBU resulted in a smooth consumption of 1 a. After the usual workup, bicyclic adduct 4 a was isolated in 72 % yield as a mixture of two diastereomers. GC analysis revealed that the diastereomeric ratio was 88:12 (Scheme 1, Table 1, entry 1).
Cyclopropanation from b-nitroamide 1 occurred smoothly to yield 4 in moderate to good yields. For example, treatment of 1 b with DBU, Ag 2 O and I 2 resulted in the formation of 4 b in 69 % yield (entry 2). The product ratio was found to be 83:17. When R 1 was a primary alkyl group, the diastereoselectivity was slightly lowered (entries 3 and 4).