Denitration, radical

Recently, it was reported that a nitromethyl group was reduced to the corresponding oxime by reaction with Bu3SnH in the presence of radical initiator (Eq. 7.61).68 Interestingly, primary nitro groups are selectively reduced to oximes in the reaction of the compounds containing both primary and secondary nitro groups (Eq. 7.62).69 The product of Eq. 7.60 may not be correct, but may be the oxime. 

The Henry reaction of nitroalkanes followed by denitration is a good method for the preparation of alcohols. This methodology has been applied in carbohydrate chemistry. For 

The Michael addition of nitroalkanes followed by denitration is also a useful method for the preparation of C-disaccharide. The Michael addition of glucosyl nitromethane to the levoglu-cosenone proceeds stereoselectively, and subsequent denitration gives the C-disaccharide in 

The high acidity of a-nitroketones makes it possible to perform the Henry reactions or Michael additions under extremely mild conditions. The reaction proceeds in the presence of catalytic amounts of Ph3P to give the C-C bond formation products under nearly neutral conditions. Thus, 1,5-dicarbonyl compounds78 and a-methylenecarbonyl compounds79 are prepared by the denitration of a-nitroketones, as shown in Eqs. 7.67 and 7.68, respectively. 

Ballini and coworkers have reported a simple synthesis of l-phenylheptane-l,5-dione based on the strategy of the Michael addition and denitration as shown in Eq. 7.69).80 The product is a natural product that is isolated from fungus. 

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The Michael addition of ct-nitro ketones to a,fi-unsaiurated ketones followed by radical denitration provides a useful strategy for the preparation of 1,4-diketones TPhenylheptane-1,5-dione, isolated from the decayed heart wood of aspens, is prepared by this strategy fEq... 

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 ... 

Enarnioselective nitro-dlclol reacdon Csee Secdon 3.3 or Michael reaction Csee Secdon 4.4 followed by radical denitration is useful as an altemadve indirect method of enandose-lecdve 1,3- or 1,4-addidon of alkyl anions fsee Eq. 7.70 and Eq. 7.71 . ... 

Other applications of radical denitration in organic synthesis are summarized in Table 7.3. 

Hesse and coworkers have used this strategy for the preparation of various macrolides.173 For example, Michael addition of 2-nitrocyclodecanone methyl vinyl ketone followed by reduction with (5)-alpine-hydride gives the nitrolactone in 72% yield. Radical denitration of the nitrolactone with Bu3SnH gives (+)-(5)-tetradecan-13-olide in 44% yield (Eq... 

Dianions derived from cyclic a-nitro ketones have been used for the preparation of the natural product phoracanthlide and related macrocyclic lactones (see Scheme 5.2).13 Alkylation of dianion of a-nitro cyclic ketones is followed by radical denitration with Bu3SnH (see Section... 

Gem-nitro imidazolyl alkanes undergo Sjy l reactions with the anion of various nitroalkanes, as shown in Eq. 5.36.54 The nitro group is replaced by hydrogen in 80-90% yield on treatment with Bu3SnH (see Chapter 7, which discusses radical denitration). 

Extension to carbocyclization of butadiene telomerization using nitromethane as a trapping reagent is reported (Eq. 5.48).72 Palladium-catalyzed carbo-annulation of 1,3-dienes by aryl halides is also reported (Eq. 5.49).73 The nitro group is removed by radical denitration (see Section 7.2), or the nitroalkyl group is transformed into the carbonyl group via the Nef reaction (see Section 6.1). 

As the nitro group is removed by radical denitration with Bu3SnH, allylic alkylation of a-nitro ketones with allyl carbonates in the presence of Pd(0) followed by denitration with Bu3SnH provides a new regio-selective allylation of ketones under neutral conditions (Eq. 5.55).79... 

Enantioselective nitro-aldol reaction (see Section 3.3) or Michael reaction (see Section 4.4) followed by radical denitration is useful as an alternative indirect method of enantioselective 1,2- or 1,4-addition of alkyl anions (see Eq. 7.7087 and Eq. 7.7188). 

The reduction of nitro ketones with baker s yeast is a good method for the preparation of chiral nitro alcohols.89 The reduction of 5-nitro-2-pentanone with baker s yeast gives the corresponding (5)-alcohol, which is an important chiral building block. Various chiral natural products are prepared from it. In Scheme 7.16, the synthesis of the pheromone of Andrena haemorrhoa is described, where the acylation of the chiral nitro alcohol followed by radical denitration is involved as key steps.89a... 

Dauzonne has reported a simple synthesis of flavanones by radical denitration and dehalo-genation of 3-chloro-2,3-dihydro-3-nitro-2-aryl-4T/- I-benzopyran-4-ones,92 which are readily prepared by the reaction of salicylaldehydes with l-chloro-l-nitro-2-arylethenes (Eq. 7.73).93... 

Sequential Michael additions are versatile methods for the construction of cyclic compounds. Although a variety of these reactions have been developed, the use of alcohols as nucleophiles for the Michael addition to nitroalkenes has been little studied. Recently, Ikeda and coworkers have reported an elegant synthesis of octahydrobenzo[b]furans via the sequential Michael addition of 1-nitro-cyclohexene with methyl 4-hydroxy-2-butynoate in the presence of t-BuOK followed by radical denitration (Eq. 7.74).94... 

The Diels-Alder reaction followed by radical denitration provides a useful strategy for construction of six-membered compounds, in which the nitro group accelerates the reaction and also controls the regio-chemistry of the addition (Eq. 7.75).95... 

Thus, radical denitration has developed as a reliable tool in organic synthesis and has been mainly carried out using tin hydride in total syntheses of natural products. There is one report in which NaTeH was used for removing the nitro group. Norslanadione, a biologically active... 

The difficulty in controlling the regiochemistry during radical-denitration of allylic nitro compounds is well known. The migration of the double bond is a serious problem, as shown in Eq. 7.96. This problem is overcome by a hydride transfer reaction in the presence of a palladium catalyst (Eq. 7.97).140... 

The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

In a recent application of this strategy, nitrocyclohexane 143 (prepared from nitrosugar 142 by intramolecular Henry reaction) was subjected to a radical denitration by HSnBu3, after protection of the hydroxyl groups to avoid side reactions. Inositol 146 was selectively obtained in good yield, once the hydroxyl protecting groups were removed (Scheme 45).101... 

Radical denitration of nitro-substituted isoxazolidines was accomplished with tributyltin hydride and 2,2 -azobis-isobutyronitrile (AIBN) in refluxing benzene <2003S1419>. 

The nitro group, as one of the many functional groups with a strong electron-withdrawing effect, plays an extremely important role in the reactivity of the sugar molecule no matter where it is located. The anomeric nitrates introduced by Vasella [53] are particularly useful reactive synthons for introducing additional functionalities via formation of the C-C bond by Henry aldol condensation [54] followed by a radical denitration. 

Upon removal of the isopropylidene groups, Michael addition occurs providing the C-linked disaccharide 75 after acetylation, together with the tetrahydrofuranyl isomer (25% yield). Radical denitration and deacylation afford the C-linked S,/3-trehalose 76. 

C-nitrosyl compound 201 with paraformaldehyde and acetylation gave /9-C-gly-coside 202 after radical denitration with Bu3SnH. Reductive dehalogenation of the... 

Danishefsky also investigated the development of a trans Diels-Alder reaction in seeming violation of the inherent stereoselectivity of the reaction mechanism. The key to this process was the use of 1-nitrocyclohexene (80) as the dienophile. After a standard intermolecular Diels-Alder reaction with diene 79, cis cycloadduct 81 could be transformed preferentially into trans-fused product 82 upon radical denitration and enol ether hydrolysis. ... 

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