Nitroalkanes allylic substitution

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

The resulting derivatives were applied with success in the standard asymmetric allylic alkylation (up to 97 % ee) [134, 136] or in transformations involving either specific allylic substrates (2-cycloalkenyl derivatives, up to >99% ee) [135, 137], unsymmetrical substrates (monosubstituted allyl acetate, up to 83% ee) [140], or especial nucleophiles (nitroalkanes [141], iminoesters [138 a], or diketones [139, 140, 142]). Such ligands were also effective in the formation of quaternary chiral carbon through allylic substitution (eq. (6)) [138, 143], deracemiza-tion of vinyl epoxides (up to 99% ee) [144], or alkylation of ketone enolates [138 b], and deracemization of allylic derivatives [145]. 

Subsequently, Kim and co-workers " followed a similar strategy using different conditions to obtain 2-arylidene-4-nitroalkanoates 238 directly via an iSN2 -type allylic substitution (Path I, Scheme 3.93) and 2-methylene-4-nitroalkanoates 239 via treatment of in situ generated DABCO salt with nitroalkanes (Path II, Scheme 3.93). Finally, they transformed these adducts into the corresponding keto esters 240 and 241, respectively, via a Nef reaction (Scheme 3.93). 

A highly enantioselective and regioselective allylic substitution of the BH carbonates using nitroalkanes as nucleophiles was developed by Lu and co-workers [135] in the presence of quinidine-derived thiourea catalyst 76. The nitroalkanes was added to the BH carbonates in the 3 position (as depicted in Scheme 9.36) in good yields and enantioselectivities (Scheme 9.38). 

Palladium-catalyzed Allyllation Reactions. Palladium-catalyzed asymmetric allylic substitutions by soft nucleophiles are an extensively studied research area in organic chemistry with huge advances in ligand development and enantiocontrol seen in the past two decades. A typical asymmetric allylic substitution reaction with malonate is shown in eq 29. Diastereo- and enan-tioselective allylation of substituted nitroalkanes has also been reported. BSA has been used as a standard base in these reactions and functions satisfactorily. 

In order to treat influenza infections, the development of neuraminidase inhibitors is required. The currently available compounds are not potent enough, and they have a number of side effects. The stereoselective total synthesis of one potent inhibitor, BXC-1812 (RWJ-270201), was achieved by M.J. Muller and co-workers. The key intermediate substituted nitromethane was prepared via a Pd-catalyzed allylation of nitromethane under basic conditions. The transformation of this nitroalkane to the corresponding carboxylic acid methyl ester was carried out in two steps. The Nef reaction was conducted in DMF instead of the usual DMSO because DMSO as the solvent caused extensive epimerization of the product. The initially formed carboxylic acid was then esterified. 

Excellent nucleophiles in palladium(0)-eatalyzed allylic alkylations are soft carbanions, i.e.. metal salts of C — H acids with a pKa in the range of 10-20. These are activated methylene compounds which are substituted with at least two geminal electron-withdrawing groups [CO.R, S02R, — CN, —NC. COR, N02, (C6H5)2C = N]. As an exception, deprotonated simple nitroalkanes are sometimes also effective as nucleophiles. 

N,N DIPROP YL-4-TRIFLUORO-METHYL-2,6-DINITROANILINE (1582-09-8) Ci3HjsF3N304 Combustible solid (flash point >185 F/>85°C oc Fire rating 1). May react violently with barium, potassium, sodium. Incompatible with organic anhydrides, acrylates, alcohols, aldehydes, alkylene oxides, substituted allyls, cellulose nitrate, cresols, caprolactam solution, epichlorohydrin, ethylene dichloride, isocyanates, ketones, glycols, nitrates, phenols, vinyl acetate. Exothermic decomposition with maleic anhydride. May increase the explosive sensitivity of nitromethane. Reacts with nitroalkanes, forming explosive products. As a dinitroaniline derivative, the extremes of heat (do not store above 90°F/32°C), mechanical shock, and fnction might be... 

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