An Improved and Easy Method for the Preparation of 2,2-Disubstituted 1-Nitroalkenes

Abstract

Reactions of ketones 1, nitromethane 2, and catalytic amount of piperidine 3 in the presence of mercaptan 6 generate beta-nitroalkyl sulfides 7-9. At 0 degrees C and by the use of dichloromethane as solvent, beta-nitroalkyl sulfides 7-9 can be oxidized by m-chloroperoxybenzoic acid (m-CPBA) 10 to generate beta-nitroalkyl sulfoxides 11-13 and undergo elimination in carbon tetrachloride solution to produce medium to high yield of 2,2-disubstituted 1-nitroalkenes 5. The irreversibility of the synthetic mechanism not only can overcome the reversibility of the Henry reaction in the synthesis of 2,2-disubstituted 1-nitroalkenes 5 but also can generate the major products "exo-nitro olefins"5c-e when cyclic ketones 1c-e were used. Under similar conditions, medium to high yield of 5-substituted-2-nitromethyl-2-phenylthioadamantane 17 also can be prepared from the reaction of 5-substituted-2-adamantanones 15, nitromethane 2, piperidine 3, thiophenol 6a. The intermediate17 can be oxidized by m-CPBA 10 in dichloromethane solution and then undergo elimination at room temperature or can be dissolved in solvent, coated on silica gel, and then heated at 90-100 degrees C to generate 5-substituted-2-nitromethyleneadamantane 16.

Convenient Synthesis of Highly Functionalized, 3,4-Disubstituted Indole Building Blocks

“…Exposure of 29 to the previously employed Olah's conditions allowed the preparation of iodide 30, which furnished nitro derivative 31 in moderate yield, together with alcohol 29, upon treatment with sodium nitrite and urea in dimethylformamide. Compound 31 was then submitted to literature conditions that allow to carry out the Henry reaction between nitroalkanes and ketones by displacing the unfavourable equilibria through reaction of the nitroaldol adduct with a thiol [24]. Unfortunately, all our attempts at translating these conditions into an intramolecular reaction allowing the preparation of compound 32 from 31 were unsuccessful.…”

Post-Translational Modification of Proteins Mediated by Nitro-Fatty Acids in Plants: Nitroalkylation

“…Reactive oxygen and nitrogen species (ROS and RNS) can cause the oxidation of the bond between the sulfur residues and the α-carbon of the NO 2 -FAs (Michael adduct) resulting both in the generation of sulfoxides and derived species and the scission of the Michael adduct. This process results in the releasing of the nitroalkene which enables the protein to recover its initial state [22,66,81,88,90,91]. The reversible possibilities of nitroalkylation in biological processes are of considerable importance, as irreversible PTMs usually lead to permanent loss of function, and thus protein degradation [22,46,68].…”

Highly Enantioselective Hydrogenation of β,β‐Disubstituted Nitroalkenes

“…This may be attributed to the steric hindrance produced by a group in the ortho position on the substrate. When the substituent was located in other ring positions, all substrates were hydrogenated with uniformly high conversions and enantioselectivities (Table 3, entries [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Compared with the ortho-bromo substrate (Table 3, entry 2), nitroalkenes with a bromo substituent in the meta or para positions gave full conversions with good enantioselectivities (Table 3, entries 6 and 12).…”