A-nitroalkenes

Scheme 2.23 provides some examples of conjugate addition reactions. Entry 1 illustrates the tendency for reaction to proceed through the more stable enolate. Entries 2 to 5 are typical examples of addition of doubly stabilized enolates to electrophilic alkenes. Entries 6 to 8 are cases of addition of nitroalkanes. Nitroalkanes are comparable in acidity to (i-ketocslcrs (see Table 1.1) and are often excellent nucleophiles for conjugate addition. Note that in Entry 8 fluoride ion is used as the base. Entry 9 is a case of adding a zinc enolate (Reformatsky reagent) to a nitroalkene. Entry 10 shows an enamine as the carbon nucleophile. All of these reactions were done under equilibrating conditions. 

Another combination of hetero-Diels-Alder reactions and a [3+2] cycloaddition of a nitroalkene was described by Avalos and coworkers [46]. Using the chiral substrate 4-134 derived from a sugar, the domino process can be performed as a three-component transformation using an electron-rich dienophile and an electron-poor... 

A radical approach to asymmetric aldol synthesis, which is based on the radical addition of a chiral hydroxyalkyl radical equivalent to a nitroalkene, has been reported, as shown in Eq. 4.93.113 The radical precursor is prepared from the corresponding carboxylic add by the Barton reaction,114 which has been used for synthesis of new (3-lactams.115... 

Dinitro-ll-oxatricyclo[6.2.1.01,6]undec-9-ene has been prepared by an intramolecular Diels-Alder reaction of the furan with a nitroalkene group as shown in Eq. 8.26. This tricyclic compound is a versatile synthetic tool for the preparation of ergot alkaloids.41... 

The palladium-catalysed decarboxylative carbonylation of 5-vinyloxazolidin-2-ones 218 caused, unexpectedly, a ring enlargement process to 5-lactams 219 <00JA2944>. The conjugate addition of 4-phenyloxazolidin-2-one to a nitroalkene was used for the synthesis of diastereoisomers of dethiobiotin <00EJO3575>. Attempted deprotection of the O-TBDMS... 

Silylation of Products of Conjugated Addition of Nucleophiles to a-Nitroolefins Nitroalkane anions can be generated not only by deprotonation of nitroalkanes (various modifications of these process were considered above) but also by the conjugated addition of nucleophiles 56 to a-nitroalkenes (42) (Scheme 3.56, Table 3.2). 

The chemistry of acyl nitronates derived from secondary AN has received much more attention. Yoshikoshi and coworkers (226-228) developed a reliable procedure for the synthesis of these derivatives from readily available precursors (ketones and a-nitroalkenes), they demonstrated that the resulting acyl nitronates (123) are convenient reagents for the preparation of various heterocyclic and acyclic derivatives (226) (Scheme 3.104). 

Professor Seebach and coworkers (96) used silyl enolate (203) containing an additional C,C double bond in the Michael reaction with a-nitroalkene (204) in the presence of chiral LA (Scheme 3.146). 

Two research groups examined the approach to the synthesis and the use of six-membered cyclic nitronates by introducing chiral inductors into the molecule of the starting a-nitroalkene. (Here, it is incorrect to use the term auxiliaries because the chiral fragment is not eliminated and is involved in the target product.)... 

The synthesis of chiral a-nitroalkenes (296) from galactose was documented (157) (Scheme 3.180). 

Intramolecular nitrile oxide cycloaddition. The conjugate addition of t-butyl isocyanide to a nitroalkene can generate a nitrile oxide, which can be trapped intramolecularly by a double bond to form an isoxazoline. 

Reaction of nitromethane and monosaccharide-derived dialdehydes is a useful tool that has been broadly used for the preparation of nitro and amino sugars, and carbocycles.30 Dialdehydes can easily be obtained by oxidative cleavage of conveniently protected monosaccharides with sodium periodate. Their subsequent Henry reaction with a nitroalkene, commonly nitromethane, usually gives isomeric mixtures that require the isolation of the major isomer.31 Thus, treatment of the D-ribose derivative 27 with sodium periodate gave dialdehyde 28, which was subjected to a Henry reaction with nitromethane, to afford nitrosugar 29 as an epimeric mixture (Scheme 11).32... 

Under basic conditions, a-nitroalkenes function as synthetic equivalents of allylic nitro compounds 3-nitro-3-hexene, for instance, reacts with piperidine in the presence of Pd(PPh3)4, to give 2-piperidinyl-3-hexene (equation 139)459. 

Solutions of acetyl nitrate, prepared from fuming nitric acid and acetic anhydride, can react with alkenes to yield a mixture of nitro and nitrate ester products, but the /3-nitroacetate is usually the major product. ° Treatment of cyclohexene with this reagent is reported to yield a mixture of 2-nitrocyclohexanol nitrate, 2-nitrocyclohexanol acetate, 2-nitrocyclohexene and 3-nitrocyclohexene. °/3-Nitroacetates readily undergo elimination to the a-nitroalkenes on heating with potassium bicarbonate. /3-Nitroacetates are also reduced to the nitroalkane on treatment with sodium borohydride in DMSO. ... 

The reaction of a-nitroalkenes with nitrogen dioxide or its dimer, dinitrogen tetroxide, has been used to synthesize polynitroalkanes. Thus, the reaction of dinitrogen tetroxide with 2,3-dinitro-2-butene (6) and 3,4-dinitro-3-hexene is reported to yield 2,2,3,3-tetranitrobutane (7, 25 %) and 3,3,4,4-tetranitrohexane (32 %) respectively. ... 

A mixture of silver nitrite and iodine reacts with alkenes to give jS-nitroalkyl iodides, and therefore, provides a convenient route to a-nitroalkenes. Treatment of alkenes with ammonium nitrate and trifluoroacetic anhydride in the presence of ammonium bromide, followed by... 

The conjugate 1,4-addition of nitronate anions and other nucleophiles to a-nitroalkenes constitutes an important method for the synthesis of polynitroaliphatic compounds. ° Nitroform (112) reacts with nitroethene (135) and 2-nitropropene to yield 1,1,1,3-tetranitropropane (136) and 1,1,1,3-tetranitrobutane respectively. A number of examples of additions of 1,1-dinitroethane, 1,1-dinitropropane and 1,1-dinitrobutane to nitroalkenes have been reported. Feuer and co-workers reported the synthesis of 1,3,3,6,6,8-hexanitrooctane (137) from the reaction of 1,1,4,4-tetranitrobutane (30) with nitroethene under basic conditions. 

Synthetic routes to a-nitroalkenes have been discussed in previous sections. General routes include (1) treating /3-nitroacetates with alkali metal acetates, carbonates or bicarbonates, (2) elimination of water from /3-nitroalcohols via heating with phthalic anhydride or in the presence of a base," ° and (3) degradation of the Mannich products derived from a primary nitroalkane, formaldehyde, and a secondary amine. ... 

Some 1,3-dinitroalkanes (145) have been synthesized from the reaction of nitroalkanes with a-nitroalkenes (144) generated in situ from the decomposition of Mannich bases (143) derived from primary nitroalkanes. Reported yields for these reactions are low and the formation of by-products limits the feasibility of the method. 

Nielsen and Bedford synthesized gem-dinitroalkanes (147) from the Michael addition of organolithium reagents to a-nitroalkenes (146) followed by quenching of the resulting nitronate anion with tetranitromethane. The same reaction using alkoxides as bases provides P-alkoxy-gem-dinitroalkanes (148). ... 

Feuer and Miller synthesized 3,5,8,10-tetranitro-5,8-diazadodecane (183) and 3,8-dimethyl-2,4,7,9-tetranitro-4,7-diazadecane (184) from the reactions of ethylenedinitramine with 2-nitrobutyl acetate and 3-nitro-2-butyl acetate respectively the latter reagents readily undergo elimination in the presence of sodium acetate base to give the corresponding a-nitroalkenes. 

Mobashery and co-workers also reported the synthesis and inhibitory apph-cation of 2 -N02 derivatives of neamine and kanamycin (Scheme 4.28). Using the metal-chelating method, the 2 -NH2 was selectively unmasked and then oxidized into 2 -N02, which will increase the acidity of 2 -H. Upon phosphorylation at the 3 -0H, elimination of phosphate will lead to the formation of a nitroalkene intermediate, 198, that can function as a Michael acceptor and... 

Figure 8. Formation of a carbohydrate nitrocyclopropane from a nitroalkenic sugar via a pyrazoline.

Parallel chemistry has been employed with 106 to afford the diaminopyrrolopyrimidines 107. Michael addition of a nitroalkene with 106 gives intermediate 107a (Scheme 10), which undergoes a Nef reaction to produce 107b and thence 108 <1999TL4027>. An alternative route is the reaction of 106 with an a-bromoaldehyde to form 108 <19990PD184>. 

The low temperature (-110 to -78 °C)51 addition of organolithiums to p-substituted-a-nitroalkenes (40) affords intermediate nitronate anions which can be quenched with either a proton source or tetra-... 

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