Allylation of nitro compounds

The problem of a- -allylation of nitro-compounds has been addressed. One report stated that a-nitroalky1 radicals, generated from a-nitrohalides in the presence of AIBN, were sufficiently... 

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

The Michael addition of nitro compounds to electron-deficient alkynes affords allylic nitro compounds in good yields, in which KF-/j-Bu4NC1 in DMSO is used as a base and solvent (Eq. 4.118).161... 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

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... 

In 1981, it was demonstrated (70) that anions of nitro compounds can be involved in C,C-coupling with allyl acetates at the allylic carbon atom with the use of metal complex catalysis. For many years, this observation did not come to the attention of chemists interested in the synthesis of cyclic nitronates. However, Trost demonstrated (71) that this process can be used in the synthesis of five-membered cyclic nitronates from olefins (18) containing two acyl groups in the different allylic positions (Scheme 3.21). 

The first demonstration of fluorous synthesis was in the preparation of small (8-12 members) isoxazo-line and isoxazole libraries by the three-step procedure outlined in Figure 8.1461 All reactions were purified by three-phase liquid-liquid extraction. The starting substrates were simple allylic alcohols which were tagged with the fluorous silyl halide 5 to make substrates 6 for an ensuing dipolar cycloaddition. This was conducted by the Mukaiyama method with a large excess of nitro compound and... 

Step (Scheme 1.220) [306]. The treatment of nitro compounds with Ag20, DBU, and iodine resulted in bicyclic cyclopropanes 470 and 471 in good yields. The stereoselectivity was generally high. The stereoselectivity depended on the size of the formed ring. The precursors 469 were readily prepared by the conjugate addition of allylic or homoallylic nucleophiles to nitroalkenes. A similar cyclo-propanation has also been reported [307]. 

Mainly allylic esters are used as the substrates for the catalytic reactions. In addition, the allylic compounds shown are known to react with Pd(0) to form TT-allylpalladium complexes. Even allylic nitro compounds[8,9] and sul-fones[KM2] are used for the allylation. The reactivities of these allylic compounds arc very different. 

Allylic nitro compounds form rr-allylpalladium complexes by displacement of the nitro group and react with nucleophiles, and allylation with the tertiary nitro compound 202 takes place at the more substituted side without rearrangement to give 203[8,9,128]. 

Various terminal allylic compounds are converted into l-alkenes at room temperature[362]. Regioselective hydrogenolysis with formate is used for the formation of an exo-methylene group from cyclic allylic compounds by the formal anti thermodynamic isomerization of internal double bonds to the exocyclic position[380]. Selective conversion of myrtenyl formate (579) into /9-pinene is an example. The allylic sulfone 580 and the allylic nitro compound... 

Allylic nitro compounds are obtained by the reacdon of cyclic ketones with nitromethane in the presence of 1,2-diaminoethane fl mol% as catalyst. Because exa-cyclic nitroalkenes are rearranged to the fi)iifo-cyclic fi,Y-nitroalkenes, allylic nitro compounds are selecdvely produced fEq. 3.21. ... 

The Henry reaction of ketones with nitroalkanes in the presence of etbylenediamine gives allylic nitro compounds, which give a,fi-imsanirated carbonyl compounds via the Nef reaction fEq. 6.30. ... 

Recently, elegant synthesis of ruin -MRS carbapenum has been reported. Sequential reaction of nitromethane via conjugate addition-elimination to a,fi-unsanirated esters followed by Pd-catalyzed subsdnidon of the residdng allyl nitro compound with the naphthosultam affords the allyladon product which is an and fEq. 7.20. ... 

The Knoevnagel reaction of 6-methoxytetralc nediamine followed by the nitro-aldol reach allylic nitro compounds Subsequent group Base catalyzed cyclizadon gives the I by radical denitration fsee Section 7 2 ... 

Acylation of the nitronate 9-71 leads to the iminium ion 9-72 which, by the addition of an isocyanide, forms the cation 9-73. Following two acyl group migrations, the compound 9-75 is obtained via 9-74. The best results were obtained when allylic nitro derivatives were used, as these can form the corresponding enolate in the presence of NEt3. Aliphatic nitro compounds could also be employed, but in these cases it was necessary to use the more basic DBU. 

Conjugated nitroalkenes are isomerized to allylic nitro compounds under basic conditions. Reactions of a,P-unsaturated nitro compounds with aldehydes under basic conditions lead directly to y,8-unsaturated P-nitro alcohols (Eq. 3.24). 3 This reaction is very useful for preparing allylic nitro compounds. 

The reaction of conjugated nitroalkenes with oc,P-unsaturated esters, ketones, nitriles, and sulfones is catalyzed by TMG to give the Michael adduct of allylic nitro compounds (Eq. 4.108).142... 

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