Synthesis of nitroalkenes

The synthetic applications of this reagent to the synthesis of nitroalkenes have been known since the 1960s.60 Nitration of alkenes with nitryl iodide, generated in situ from iodine and silver nitrite, is convenient for the synthesis of P-nitrostyrenes with various functional groups.61 This method is applied to the synthesis of ortho-methoxylated phenylisopropylamines, which are potent serotonine agonists (Eq. 2.31).62... 

Emmons-Wadsworth reaction. Very mild bases (e.g., KaCO,) are required for the synthesis of nitroalkenes using these reagents. 

Mechanisms of Fatty Acid Nitration Chemical and Cell Synthesis OF Nitroalkenes... 

A simple and practical method for the one-pot synthesis of nitroalkenes has been developed using a cooperative catalysis system involving piperidine and iron(III) chloride. This dual catalytic protocol simultaneously activates both electrophile and nucleophile. 

In our group, we have described the synthesis of nitroalkenes starting from iodo-glycosides via a novel tandem metallation-elimination-Henry reaction [60]. The reaction can be promoted either by the metal system zinc-indium or by n-BuLi, leading to different results in both cases. Thus, reaction of 5-iodo-ribofuranoside 3 with bromonitromethane in the presence of zinc (10 equivalents) and indium (1 equivalent) in THF/H2O 4 1 under sonication at 40°C, afforded a 5 4 mixture of nitrohexene 76 and bromonitrohexene 77, from which nitrohexene 76 was isolated in a 39% yield... 

In 1985, in the course of their interest in nitroalkane chemistry, Barton and Zard reported the base-catalyzed reaction of nitroalkenes with a-isocyanoacetates leading to pyrrole esters having an ideal substitution pattern for the synthesis of porphyrins and bile... 

The synthesis of cyclic nitroalkenes via nitradon of cyclo ilkenes is sttmmarized in Table 3 3 Acyclic nitro ilkenes are more readily prepared via the Henry reacdon than by nitradon of ilkenes fsee Secdon 3 3 1 ... 

OxiddQon of oximes to rutro compounds with w-CPBA has been applied to the synthesis of dialkyl l-nitroalkanephosphonates fEq 2 63, which are useful reagents for d carbonyl compounds to nitroalkenes... 

A stereospecific total synthesis of polyoxin C and related nucleosides is reported, in which thereacdon of l-Cphenylthioi-l-nitroalkenes v/ith nucleophiles and siibseqiientozono lysis are key reacdons Addidonof potassium trimethylsilanoate to l-Cphenylthioi-nitroalkenes derived from D-ribose followed by ozonolysis gives the cr-hydroxy thioester, which is formed v/ith excellent diastereoselecdvity fScheme 4 5 This conformadon meets the stereo-electronic requirements for andperiplanar addition of the nucleophile with the result of high 5-fS stereochemical bias in the reacdons... 

Jackson and coworkers have used a new approach to the synthesis of fi-hydtoxy-ct-amino acids using farylthio nitrooxiranes. c-Jsopropylideneglyceraldehyde is converted into the corresponding 1-arylthio-l-nitroalkene, which is a key material for stereoselective synthesis of fi,Y-dihydroxyamino acids fScheme 4.6. The key step is stereoselective nucleophilic epoxlda-donof the Tarylthio-Tnltroalkene. Sy)i and ruin epoxides are selecdvely obtained by appropriate choice of epoxidadon reagent." ... 

A short synthesis of ptostaglandm derivatives via a three component coupling reaction reported, in which the enolates are trapped v/ith nitroalkenes. The nitro group is removed v... 

This procedure Is applied to synthesis of 1,3-diamines by the addition ofmetdlated rerr-biityl iV.iV-dimethylcarbamate to nitroalkenes and subsequent reduction fEq. 4.84. ... 

The Michael addition of the copper-zinc reagent derived from ethyl 4-bromobntyrate to the plperonal-derived nitroalkene proceeds cleaniy to give the nitre ester, which is an intermediate for the synthesis of lycoricidine alkaloids fEq. 4.85. ... 

The direct conversion of nitroalkenes into ketones is especially useful for the preparation of arylacetones. They are readily prepared by the condensation of aromatic aldehydes with nitroethane and by the subsequent Nef reaction. "Typical examples are presented in Eq. 6.22 and Eq. 6.23 the product of Eq. 6.23 is used for total synthesis of perylenequinone, calphosdn D, which is a potent inhibitor of protein kmase C. "... 

An intramoleculdf raLliciil cyclizdDon gives ihe exa-cyclic compounds, which has been extensively used in the synthesis of cychc compounds Michael adthdons of allyl idcohols or propargyliilcohols to nitroalkenes and the subsequent treatment v/ilhdn rathciils provide a useful method for the preparadon of sitbsdrtited ftirans fEqs 7 83 and 7 84 ... 

Node and co-workers have found that the Diels-Alder reaction of nitroalkenes v/ith 1-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s dienesi exhibit abnormal exo-se-lecdvity Electrostadc repulsion between the nitro and the silyloxy group of the diene induces this abnormal exc-selecdvity (Tq 8 10 This selecdve reacdon has been used for the asymmetric synthesis of various naniral products as shovm in Scheme 8 6... 

The Diels-Alder reaction of nitroalkenes with Danishefsky s dienes is applied to synthesis of truncated carbocyclic analogues of a potent neuraminidase inhibitor 4-guanidino-NemAc en fsee Scheme 8.5. Carbocyclic analogs are found to retain interesting levels of antiviral activity comparable to those shovm by their oxygen-containing compounds in Scheme 8.5. 

Node and coworkers have used this aromadzadon strategy for the synthesis of (-) aphanor-phineThe Diels-Alder reacdon of chiral nitroalkene, prepared by the asymmecdc nitrooleft-nation reacdon of ct-methyl-o-valerolactone, with the Danishefsky s diene followed by aromadzadon is used as a key step for this total synthesis, as shown in Scheme 8 6... 

Node and Fuji have developed a new chiral synthesis of various alkaloids using chiral nitroalkene, fS -( - -3-methyl-3-( 3 -nitrovinyl -o-valerolactone Scheme 8 11 shows a total synthesis of f-i-physosdgmine, a principM alkriloid of the CMabar bean The key nitroalkene is prepared by asymmetric nitroolefinadon of ct-methyl-o-lactone using a chirM enamine fsee... 

When Talkoxy-l,4-pentadienes are used Instead of 2-alkoxy-l,4-pentadienes, tandem Inter [4- 2 /lntra [3- 2 cycloaddidon of nitroalkenes followed by hydrogenolysls affords a versatile asymmetric synthesis of highly fiincdonalized aminocyclopentanes fScheme 8.47i. ... 

The Michael addidon to nitroalkenes followed by cyclizadoti provides a getieriil method for the synthesis of various pyrroles. The reacdoti of nitroalkenes v/iih acetoacetate followed by reducdoti v/ith Znin acedc acid provides another route to 3-methyl-3-pyrrolecarboxylates fEq. 10.8. °... 

Barton and Zard found that the base-catalyzed reacdon of nitroalkenes or fi-n v/ith alkyl isocyanoacetate or TosMIC gives pyrrole-3-carboxylates or 3-suifonylpyrroles, respecdvely fsee Eqs 10 18 and 10 19) This reacdon is very convenient for the synthesis of... 

Nitroalkenes are shown to be effective Michael acceptor B units In three sequential re fA + B + C couplingi in one reaction vessel. The sequence is initialed by enolate nucleophiles fA and is terminated by aldehydes or acrylate electrophiles fC. The utility of this protocol is for rapid assembly of complex stnictures from simple and readily available components. A short total synthesis of a pyrroLmdine alkaloid is presented in Scheme 10.16. ... 

The Michael addition of the carbanions derived from esters to nitroalkenes followed by reductive cycLizadon has been used extensively for the preparation of pyrrondin-3-ones fEq 1076 This strategy is used for synthesis of the carbaaole alkaloid staurosporine aglycon CK-352c ... 

Hoashi, Y., Yabuta, T., Takemoto, Y. (2004) Bifunctional Thiourea-Catalyzed Enantioselective Double Michael Reaction of y,5-Unsaturated fS-Ketoesterto Nitroalkene Asymmetric Synthesis of (—)-Epibatidine. Tetrahedron Letters, 45, 9185-9188. 

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