Alkenes electron-deficient, reduction

Although simple isocyanates are not electrophilic enough to add to alkenes, electron-deficient isocyanates will add to alkenes. Chlorosulfonyl isocyanate is the most reactive and most commonly used isocyanate105-107. It undergoes stereospecific syn addition to alkenes. The carbonyl group adds to the most nucleophilic end of the double bond. The chlorosulfonyl group can be reductively hydrolyzed with sodium sulfite. Asymmetric induction will result from addition to... 

Alkenylation using nitroalkanes followed by the selective reduction of the double bonds with NiCl2 and NaBH4 can be regarded as the addition of alkyl anions to electron-deficient alkenes (Eq. 7.127).173... 

As indicated, the reduction of an electron-deficient alkene renders a formally electropositive carbon center nucleophilic. The fields of electrohydrodimerization and electrohydrocyclization are a direct consequence of this realization [1, 2]. The former corresponds to the dimerization of an electron-deficient alkene via a process that couples the electron-deficient -carbons of the substrate. Overall, two electrons and two protons are consumed. Electrohydrocyclization is the intramolecular counterpart of this process. 

Many reductive cyclizations, including many of those that are not initiated electrochemically, correspond to variations on the electrohydrocyclization theme. The so-called electroreductive-cyclization reaction, for example, involves cyclization between the /I-carbon of an electron-deficient alkene and an aldehyde or ketone tethered to it, to form a new a-bond between these formally electron deficient centers (Scheme 2). 

Substrates for EHC reactions consist of two electron-deficient alkenes tethered to one another. Reduction leads to the formation of an adduct wherein the )S-carbons are joined by a new sigma bond. As illustrated in Table 1, the methodology is exceptionally useful for the construction of three-, five-, and six-membered rings, but not for rings of sizes seven and eight. 

The mercurio ketone 4 upon reduction with NaBH4 yields a radical which is trapped in situ by reactive acceptors such as vinyl ketones [37]. Treatment of a 1 3 mixture of mercurio ketone 4 and electron deficient terminal alkenes (or fumarate) in CH2C12 with a concentrated solution of NaBH4 in water gives conjugate adducts, Eq. (36). 

Similar to the tin- and zinc-based methodologies, electron deficient alkenes were found to strongly catalyze the reductive elimination step.155 156-395 Organomercury reagents are also believed to add via metal addition.385... 

The opposite regioselectivity observed for the addition of methylbutenyltin to similar allyl substrates (equations 241 and 242),137>139 caused by the presence of maleic anhydride in the latter case (equation 242), may be viewed as support for a change in mechanism when the electron deficient alkene ligand is present. Conversely, both reactions could proceed by metal addition, with the regiocontrol exercised by the maleic anhydride acting in the addition-reductive elimination sequence. 

As will become evident in this section, in the net transformation from reactant —s-product transformations many of the synthetically useful reactions involving >C=C<"+ are analogous to those involving neutral, un-ionized carbon-carbon double bonds (e.g. the Diels-Alder reaction, oxidation/reduction reactions, nucleophilic addition etc.). However, many of the reactions involving a neutral >C=C< often require the presence of an activating substituent in order to make the alkene more electron-deficient. In a sense, one-electron oxidation of an alkene to its radical cation provides a simple and unique mechanism for increasing the electrophilic (and, of course, radical) properties of... 

Reductive arylation of enones, TiCl3 induces homolytic dediazotization of diazonium salts to produce aryl radicals, which arylate electron-deficient alkenes.1 Example ... 

Scheme 6.33 illustrates an example of some zinc-induced three-component coupling reactions of alkyl iodides, electron-deficient alkenes, and carbonyl compounds [51]. In this instance, the isopropyl radical is generated by a one-electron reduction of isopropyl iodide followed by elimination of iodide ion. The resulting radical then adds to acrylonitrile to form an a-cyano alkyl radical, which is con-... 

Aryl-A3-iodanes bearing an electron-deficient alkyl ligand such as aryl(sul-fonylmethyl)-A3-iodanes (Section 3.2.7) and aryl(perfluoroalkyl)-A3-iodanes are relatively stable. A series of (perfluoroalkyl)phenyl-A3-iodanes 96 were synthesized in good yields by treating bis(trifluoroacetoxy)-A3-iodanes with benzene in the presence of triflic acid [47]. The AModanes 96 transfer the perfluoroalkyl groups to a variety of nucleophiles with reductive elimination of iodobenzene. The nucleophiles involve Grignard reagents, alkyllithiums, enolate anions, alkenes, alkynes, trimethylsilyl enol ethers, arenes, phenols, and thiols. In these reactions, the AModane 96 serves as a source of the perfluoroalkyl cation and, in... 

It has been found that reductive addition of RFI to electron-deficient alkenes can lead to good yields of Ziydroperfluoroalkylation products [268,269], and Hu... 

Electron-deficient alkenes, either these with conjugating substituents or of enones, undergo Michael-like additions with regiospecific introductions of the nucleophiles, and this approach has been successful for the formation of cyclopropyl derivatives—notably from some nucleosides. An example involves the addition of the anion of bis(phenylsulfonyl)methane to the phenylselenone 173 which gives the adduct 174 in 35% yield. This reaction presumably occurs by Michael addition to C-2 followed by Sn2 ring-closure reaction at C-3 with displacement of phenylselenic acid. Reductive desulfonylation affords the 2,3,-dideoxy-2,3 -cyclopropayuridine 175.199... 

The intramolecular thermal [5+2] cycloaddition of 3-alkoxy-4-pyrones with sulfur- (e.g., 416) or silicon- (e.g., 419) tethered alkenes has been shown to occur with complete regio- and stereochemical control to give adducts 417 and 421, respectively. The adducts can be converted by reduction and oxidation, respectively, to the bicyclic products 418 and 421 (Scheme 69) <1993JOC5585>. It should be noted that this thermal [5+2] cycloaddition has not been realized in a bimolecular mode <1977JOC3976>. This methodology serves as an alternative to the reaction of electron-deficient alkenes with pyrone-derived 4-methoxy-3-oxidopyrylium ylides <1992TL2115>. 

Tandem radical addition/cydization reactions have been performed using unsaturated tertiary amines (Scheme 9.11) [14,15]. Radical attack is highly stereoselective anti with respect to the 5-alkoxy substituent of 2-(5f-J)-furanones, which act as the electron-deficient alkenes. However, the configuration of the a position of the nitrogen cannot be controlled. Likewise, tandem addition cyclization reactions occur with aromatic tertiary amines (Scheme 9.12) in this case, acetone (mild oxidant) must be added to prevent the partial reduction of the unsaturated ketone [14]. 

When these compounds were treated photochemically with electron-deficient alkenes in the presence of an excess of 1,4-cyclohexadiene, serving as hydrogen donor, reductive addition products were obtained according to the generalized scheme [78] ... 

The Reduction of Electron-deficient Alkenes with Sml2... 

Fukuzumi and Otera studied the reduction of electron-deficient alkenes in lactones and cyclic enones using Sml2.53 More recently, the use of Hilmersons Sml2 H20-amine system was shown to be effective for the selective reduction of a,p-unsaturated esters and conjugated double and triple bonds (Scheme 4.44).54,55... 

The reduction of electron-deficient alkenes is thought to proceed through a radical enolate species 59. Further reduction generates dianionic species 60 that is then protonated to give the product of reduction (Scheme 4.47). 

Fukuzumi and Otera showed that substituents at the (5-position increased the rate of reduction of the electron-deficient alkene. This supports the above mechanism as the more substituted the (5-carbon centre, the more stable is the (5-radical and the more facile the reduction (Scheme 4.48).53... 

The reduction of sulfones with Sml2 can result in deoxygenation, to give the parent sulfide,59 or carbon-sulfur bond cleavage, depending on the substrate and the reaction conditions employed.60 For example, alkyl and alkenyl phenyl sulfones are reductively cleaved by Sml2 in the presence of HMPA. In the reduction of alkenyl sulfones, competing reduction of the electron-deficient alkene is not observed (Scheme 4.50).60... 

If pyrrole would do a similar thermodynamically controlled exo Diels-Alder reaction with a vinyl pyridine, a short route to the interesting analgesic epibatidine could be imagined, with just a simple reduction of the remaining alkene left to do. The reaction looks promising as the pyridine makes the dienophile electron-deficient and pyrrole is an electron-rich diene . 

The HuangMinlon reduction of 3-formylfuran gives 3-methylene-2,3-dihydrofuran. The product undergoes ene reactions with a number of electron-deficient alkenes and provides a route to functionalize the 3-position in furan as shown in Scheme 132. 

Photooxetane formation is quite inefficient, a fact which usually points to the presence of an intermediate which can partially revert to ground state reactants. Cleavage of the diradical must be responsible for some of the inefficiency in oxetane formation 129>. However, in the past few years convincing evidence has appeared that a CT complex precedes the diradical iso.isi). The two most telling pieces of evidence are the relative reactivities of different alkenes 130> and the absence of any measurable secondary deuterium isotope effect on quenching rate constants 131>. Relative quenching rates of sterically un crowded olefins are proportional both to the ionization potentials of the donor olefins 130> and to the reduction potentials of the acceptor ketones 131>, as would be expected for a CT process. Inasmuch as n,n triplets resemble electron-deficient alkoxy radicals, such substituent effects would also be expected on direct radical addition of triplet ketone to olefin. However, radical addition would yield an inverse isotope effect (in, say, 2-butene-2,3-d2) and would be faster to 1,1-dialkylethylenes than to 1,2-dialkylethylenes, in contrast to the actual observations. 

Acetoxymercuriation of cyclopropanes. keaction of Hg(OAc), with cyclopropanes results in attack at the least substituted carbon atom. Reduction of the product in the presence of an electron-deficient alkene results in coupling of the intermediate radical to the least substituted carbon atom of the alkene. 

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