Nef-type reaction

Simple reactivity inversion" implies using an umpoled synthon whose origin has, in principle, nothing in common with the synthon with "unnatural" polarity. An example of this type of reactivity inversion is found in one of the possible synthesis of cw-jasmone (3) in which the nitroethane (4) is used as an equivalent of an "acetyl anion" and reacts with an a,P-unsaturated ketone to give the corresponding 1,4-bifunctional system which can then be transformed by a Nef-type reaction into the dissonant 1,4-dicarbonyl system [5]. An intramolecular aldol condensation finally affords the target molecule (Scheme 5.3). 

On the other hand, doubly deprotonated nitroalkenes are reagents with a double reactivity inversion (Scheme 5.30) provided they are used to prepare normal 0-, A-derivatives [1]. For instance, the 1-nitrobutadiene dianion 43 reacts with electrophiles to give a mixture of a- and y-isomers, 44a and 44b. Addition of the dianion 43 to 2-cyclohexenone gives only the y-adduct 45 which was transfomed into the 1,7-ketoaldehyde 46 by a Nef-type reaction with TiCl3 [38]. As shown in Scheme 5.30, although the resulting product is a "consonant system" (1,7-C), the... 

Attempted Nef-Type Reaction Leads to 3-Arylpyridine Synthesis... 

Capecchi, T., de Koning, C. B., Michael, J. P. Synthesis of the bisbenzannelated spiroketal core of the y-rubromycins. The use of a novel Nef-type reaction mediated by Peariman s catalyst. Perkin 1 2000, 2681-2688. 

A number of methods to effect Nef-type reactions employ reducing agents in place of the acid/base combination. The most commonly used variant of this type was developed by McMurry in 1973 and involves treatment of nitroalkanes with aqueous TiCb. In a representative example, these conditions were used for the conversion of 20 to 21 in 85% yield. These reactions likely proceed through generation of a Ti-0 bond to afford 22, followed by N-0 bond cleavage to yield 23. Tautomerization of the nitroso species (23) would provide oxime 24, which is then hydrolyzed to afford 21. Although these conditions are still somewhat acidic, several functional groups are tolerated... 

Dimethyl dioxirane (DMDO) has also been employed as a mild and selective oxidant in Nef reactions.19 For example, treatment of nitroalkane 31 with KOf-Bu followed by DMDO provided enone 32 in 72% yield.20 The alkene isomerization that occurred in this case was desirable, as 32 represents the AB ring system of the natural product norzoanthamine. Many other oxidants have been used in Nef-type reactions,3,4 including alkali metal percarbonates or mixtures of K2CO3 and H2O2.21... 

Michael addition of allyltrimethylsilane to a-nitro-olefins in the presence of aluminium chloride gives, following a Nef-type reaction, y,5-unsaturated... 

Asymmetric Michael addition of optically active perhydro-l,4-oxazepin-5,7-diones, and of thioglycollic acid in the presence of a cinchona alkaloid as catalyst, to a-nitro-olefins yields y-nitrocarboxylic acids and 2-nitrothio ethers, respectively, with reasonable enantiomeric excess. Allylsilanes add to a-nitro-olefins in the presence of aluminium chloride to give unsaturated nitronic acids, which are further transformed in a Nef-type reaction to give y,5-enones (Scheme 36).Nitro-compounds are also converted into the corresponding carbonyl compounds upon treatment with base and MoOs pyHMPA, a new modified Nef reaction. 

Grierson, D. S., Husson, H.-P. Polonovski- and Pummerer-type reactions and the Nef reaction, in Comp. Org. Synth, (eds. Trost, B. 

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