Tandem double acylation/[3,3]-rearrangement of aliphatic nitro compounds: a route to α-oxygenated oxime derivatives

Abstract

A novel efficient regioselective method for the carbon chain activation of aliphatic nitro compounds is described using a tandem double acylation/[3,3]-rearrangement sequence.

Sequential Acylation/Silylation/Hetero‐Claisen Rearrangement of Nitroalkanes for the Synthesis of Protected Hydroxyoxime Derivatives

“…[6a,9] Also acylation conditions for the first step should not facilitate acylation of nitronate 3 itself. [7] Next, for unsymmetric nitro compounds 1, possessing differently substituted β and β'positions, formation of two constitutional isomers 2 and 2' (via respective enamines 4 and 4') should be taken into account. Instability of acyl nitronates 3 [10] prevented the use of higher reaction temperatures for both reaction steps due to possible acyloxy-group migration in nitronate 3 as well as in cation B.…”

“…Importantly, advantage of the presented procedure is emphasized by successful functionalization of primary nitro compounds (products 2 o-r), that was not possible for previously reported double acylation protocol. [7] An increase in steric hindrance also prevented the use of DBU and required stronger alcoholate base. This accounts to nitro compounds possessing β-CH 2 and β'-CH/CH 2 groups, including cyclic nitro compounds -derivatives of cyclopentane and cyclohexane.…”

“…Regiochemical regularities were similar to those observed for double acylation protocol, that can be explained by steric reasons. [7] Thus, functionalization of methyl group was preferable competitively to the methylene group (2 a, b, h), while complete methyl group reactivity was observed for substrates possessing methyl and methyne moieties (2 ea, eb, f, i-m). As was mentioned above, for sterically hindered nitro compounds, possessing CH 2 at β-position and CH at β'-position, complete preference for CH 2 -functionalization was also observed.…”

“…To demonstrate the synthetic utility of obtained products several further transformations were performed (Scheme 12). [7,20] Firstly, oxime O-silyl group was selectively cleaved under treatment with TBAF/AcOH in THF producing oximes 6 in excellent yields. Several possibilities were demonstrated for selective deprotection of ester moiety producing free alcohol.…”

“…1 oxyphenyl)-1,4-dioxaspiro[4.5]decan-7-yl pivalate 2 w. Oxime ether 2 w was obtained from nitro compound 1 w (89 mg, 0.30 mmol), pivaloyl chloride (45 μL, 43 mg, 0.36 mmol) and TBSOTf (0.12 mL, 0.14 g, 0.52 mmol) according to GP-5 with following change: silylation stage was prolonged to 4 h. Column chromatography (eluent: PE/EtOAc, 9 : 1) afforded 115 mg (76 %) of target oxime ether as slightly yellow oil. Relative configuration was assigned based on coupling constants for CH (7) and CH(9) and NOESY specta assuming a chair-like conformation. R f = 0.51 (PE/ EtOAc, 3 : 1, UV, anisaldehyde).…”