Radical Michael addition

Benzophenone (Amax = 340 nm, log e = 2.5, n-ir electronic transition) can be used as a photochemical reagent and eq. 4.25 shows a radical Michael-addition reaction with benzophenone. The formed benzophenone biradical (triplet state, Tx) abstracts an electron-rich a-hydrogen atom from methyl 3-hydroxypropanoate (62) to generate an electron-rich a-hydroxy carbon-centered radical [III], then its radical adds to the electron-deficient (3-carbon of a, (3-unsaturated cyclic ketone (63) through the radical Michael addition. The electrophilic oxygen-centered radical in the benzophenone biradical abstracts an electron-rich hydrogen atom from methyl 3-hydroxypropanoate (62) [70]. So, an a-hydroxy carbon-centered radical [III] is formed, and an electron-deficient a-methoxycarbonyl carbon-centered radical [III7] is not formed. 

Asymmetric intermolecular radical Michael addition was investigated with a chiral aluminum reagent. As would be expected from the general difficulties encountered in the control of intermolecular radical addition, ee was low (Scheme 6.163) [209]. 

A radical Michael addition whose stet C-2 of perhydro-1-aroyl-2- -butylp Tii... 

A radical Michael addition whose steric course is dominated by the /-butyl substituent it C-2 of perhydro-1-aroyl-2-/-butylpyrimidin-4-ones occurs at C-6. After the radical is created from the action of BUjSnH on the l-(o-halobenzoyl) derivatives, a 1,5-hydrogen itom translocation takes place. The products are converted to P-amino acids on acid -ydrolysis. 

Additive Polyimides. Rhc ne-Poulenc s Kin el molding compound and Kerimid impregnating resin (115), Mitsubishi s BT Resins (116), and Toshiba s Imidaloy Resin (117) are based on bismaleimide (4) technology. Maleic anhydride reacts with a diamine to produce a diimide oligomer (7). Eurther reaction with additional diamine (Michael addition) yields polyaminohismaleimide prepolymer with terminal maleic anhydride double bonds. Cure is achieved by free-radical polymerization through the terminal double bonds. 

Maleimides have three principal reaction pathways. These are radical addition to vinyl compounds the Michael addition with compounds having active hydrogens and the Diels-Alder reaction with dienes (Fig. 3). Any of the three can be tools for forming thermosetting adhesives. 

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... 

Three possible mechanisms may be envisioned for this reaction. The first two i.e. 1) Michael addition of R M to the acetylenic sulfone followed by a-elimination of LiOjSPh to yield a vinyl carbene which undergoes a 1,2 aryl shift and 2) carbometallation of the acetylenic sulfone by R M followed by a straightforward -elimination, where discarded by the authors. The third mechanism in which the organometallic reagent acts as an electron donor and the central intermediates is the radical anion ... 

In certain cases, Michael reactions can take place under acidic conditions. Michael-type addition of radicals to conjugated carbonyl compounds is also known.Radical addition can be catalyzed by Yb(OTf)3, but radicals add under standard conditions as well, even intramolecularly. Electrochemical-initiated Michael additions are known, and aryl halides add in the presence of NiBr2. Michael reactions are sometimes applied to substrates of the type C=C—Z, where the co-products are conjugated systems of the type C=C—Indeed, because of the greater susceptibility of triple bonds to nucleophilic attack, it is even possible for nonactivated alkynes (e.g., acetylene), to be substrates in this... 

Jahn combined the formation of the enolate 2-713 resulting from an intermolecu-lar Michael addition of 2-711 and 2-712 with a radical reaction (Scheme 2.157) [363]. The enolate 2-713 did not undergo any further transformations due to the lack of appropriate functionalities. However, after formation of a radical using a mixture of ferrocenium hexafluorophosphate (2-714) and TEMPO, a new reaction channel was opened which afforded the highly substituted cyclopentene 2-715a diastereoselec-tively. 

In recent years, many novel MCRs - including Michael addition-initiated three-component domino sequences [10], Knoevenagel/hetero-Diels-Alder-based MCRs [11], radical chain MCRs [12], transition metal-catalyzed Pauson-Khand MCRs [13], as well as Petasis MCRs [14], have been added to the chemisf s armamentarium and successfully applied to all fields of organic synthesis. 

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... 

Interesting intramolecular cyclization of 1-nitroalkyl radicals generated by one-electron oxidation of aci-nitro anions with CAN is reported. As shown in Eq. 5.44, stereoselective formation of 3,4-functionalized tetrahydrofurans is observed.62 l-Nitro-6-heptenyl radicals generated by one electron oxidation of aci-nitroanions with CAN afford 2,3,4-trisubstituted tetrahydropyrans.63 The requisite nitro compounds are prepared by the Michael addition of 3-buten-l-al to nitroalkenes. 

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... 

Because reductive cleavage of aliphatic nitro compounds with Bu3SnH proceeds via alkyl radicals, nitro compounds are also used as precursors to alkyl radicals. Reactions using nitro compounds may have some advantages over other ones, since aliphatic nitro compounds are available from various sources. For example, the sequence of the Michael additions of nitro compounds provides an excellent method for the construction of quaternary carbon compounds (Eq. 7.79).126 Newkome has used this strategy for the construction of dendritic polymers (Eq. 7.80).127... 

An intramolecular radical cyclization gives the cxo-cyclic compounds, which has been extensively used in the synthesis of cyclic compounds. Michael additions of allyl alcohols or propargy 1 alcohols to nitroalkenes and the subsequent treatment with tin radicals provide a useful method for the preparation of substituted furans (Eqs. 7.83 and 7.84).126... 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

Due to the toxicity of tin reagents, a new radical elimination without using Bu3SnH is highly desirable. B arton has reported that nitro olefins are converted into olefins via radical elimination of P-nitro trithiocarbonates (Eq. 7.116).160 The Michael addition of trithiocarbonate to nitroalke-nes is carried out in CS2 to avoid the addition of EtSH. 

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