Nucleophilic reactions vinylic

In the synthesis of carpamic acid (98), Mitsutaka and Ogawa have used 1,2-dihydropyridine as a starting material [80H(14)169]. Photooxygenation of dihydropyridine 8h afforded enr/o-peroxide 96. Subsequent stereoselective nucleophilic reaction of 96 with ethyl vinyl ether in the presence of tin chloride gave tetrahydropyridinol 97, which was then converted into carpamic acid (98) in six more steps. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

It is worth noting that in most of the reactions involving allenes with an internal nucleophile, cr-vinyl complexes are formed but their further reaction usually lead to unwanted by-products. 

Reactions. Oxidations. Nucleophilic Reactions of Olefins. These reactions, which over-all, involve replacement of vinyllic hydride by a nucleophile (Reaction 1),... 

Vinyl epoxides and allylic carbonates are especially useful electrophiles because under the influence of palladium(O) they produce a catalytic amount of base since X- is an alkoxide anion. This is sufficiently basic to deprotonate most nucleophiles that participate in allylic alkylations and thus no added base is required with these substrates. The overall reaction proceeds under almost neutral conditions, which is ideal for complex substrates. The relief of strain in the three-niembered ring is responsible for the epoxide reacting with the palladium(O) to produce the zwitterionic intermediate. Attack of the negatively charged nucleophile at the less hindered end of the ic-allyl palladium intermediate preferentially leads to overall 1,4-addition of the neutral nucleophile to vinyl epoxides. 

The subject of this chapter is how we can achieve reaction of nucleophiles with vinyl electrophiles such as vinyl halides. We cannot easily make SN1 or SN2 reactions happen at sp2 carbon atoms but we can make the products of those unfavourable reactions by other reactions in which the same bond is formed. We want to be able to use carbon nucleophiles. We also want to control the stereochemistry of the double bond in the product. This is the disconnection we want to achieve 29 ... 

The final chapter of this section is by Rappoport and is concerned with nucleophilic reactions at vinylic carbon. Two reaction types are considered, those of neutral vinyl derivatives and those of vinyl cations. Correlation of rates for these reactions with both Ritchie and Swain-Scott equations was attempted without success. Rappoport concludes that these reactions are subject to a complex blend of polar, steric, and symbiotic effects and that a quantitative nucleophilicity scale toward vinylic carbon cannot be constructed . This conclusion is reminiscent of the earlier observation of Pearson (see the introduction to the section on the Brpnsted equation) and the later observation of Ritchie (Chapter 11) regarding the difficulty of correlating nucleophilic reactivity with a single equation. Rappoport finds another familiar situation when he explores the relationship between reactivity and selectivity for the vinyl substrates sometimes the RSP is obeyed and sometimes it is not. 

The nucleophilicities are found to be dependent on electronic, steric, and symbiotic effects, and limited series obeyed a constant selectivity , a reactivity-selectivity or a dual-parameter linear free-energy relationship. The conclusion made was that because of different blends of the effects, the construction of a substrate-independent nucleophilicity scale was impossible at present, but an approximate scale was presented. In nucleophilic reactions on relatively long lived vinyl cations, the steric effects predominate, but at constant steric effects, reactivity-selectivity relationships were found for very short series of substrates. Additional data are required for constructing more reliable nucleophilicity scales toward neutral and positively charged vinylic carbons. 

Table IV compares the reactivity ratios of a soft (PhS-) to a hard (MeO-) nucleophile in vinylic substitution. PhS is always more reactive, and ratios lower than unity, as for 4, X = Br (4), are certainly due to elimination-addition with MeO . The ratios change by >2000-fold and are sensitive to the geometry of the substrate. An important feature is that for (3-halo-p-nitrostyrenes the ratio decreases strongly with the increased hardness of the (3-halogen (38). The lowest ratios are for the (3-fluoro derivative, whereas the differences between the chloro and bromo compounds are not so large. This behavior is similar to that in SNAr reactions. This behavior can be rationalized by symbiotic effects, which favor the soft-soft PhS--Br interaction and the hard-hard MeO-F interaction. A reactivity-selectivity relationship for vinyl bromides of different electrophilicities does not exist.

A complementary part to the reaction with neutral, although polarized, vinylic carbon is the reaction of nucleophiles with vinyl cations 14 (equation 5). The data in this case are much more limited, for two reasons (1) very few vinyl cations had been prepared with sufficiently long lifetime that allows their direct reaction with nucleophiles to be followed and (2) a very few capture experiments of a solvolytically generated vinyl cation by several nucleophiles were conducted. 

The reaction mechanism and the application of the enol ether condensation in the synthesis of carotenoids have recently been reviewed [38]. The main advantage of the enol ether condensation, compared with the aldol condensation, is that the enol ether reacts exclusively as the nucleophilic reaction partner and the acetal exclusively as the electrophilic one and this leads unequivocally to the desired, uniform, reaction product. As the alkoxy group of the starting acetal takes part in the formation of the new acetal grouping that results from the enol ether moiety, it is preferable for all the alkoxy groups of both reactant to be identical. Most of the examples published have been carried out with vinyl methyl ether (16) and vinyl ethyl ether (17), used to extend the carbon skeleton by two carbon atoms, or propenyl ethyl ether (18) and 1-methoxy-1-methylethene (19) for the extension by three carbon atoms (Figure 5). 

Ketene diethyl acetals, which are more nucleophilic than vinyl ethers, add to a wide array of sulfenes to produce [2 + 2] cycloadducts36 39,207. The reaction of meth-anesulfonyl chloride with ketene diethyl acetal gave 3,3-diethoxythietane 1,1-dioxide, which can be hydrolyzed to 3-oxothietane 1,1-dioxide by concentrated hydrochloric acid (equation 97)207. The reaction of methanesulfonyl chloride with two equivalents of ketene... 

Methyl halides and primary alkyl halides undergo only Sn2 reactions, tertiary alkyl halides undergo only SnI reactions, vinylic and aryl halides undergo neither Sn2 nor SnI reactions, and secondary alkyl halides and benzylic and al-lylic halides (unless they are tertiary) undergo both SnI and Sn2 reactions. When the stmcture of the alkyl halide allows it to undergo both Sn2 and SnI reactions, the Sn2 reaction is favored by a high concentration of a good nucleophile in an aprotic polar solvent, while the SnI reaction is favored by a poor nucleophile in a protic polar solvent. 

The Co-C bond cleavage of 2-hydroxyalkylcobalt complexes does not take place via intermediate r-complexes between the Co(I) nucleophile and vinyl alcohol. There is evidence that the reaction occurs with a 1,2-hydride shift rather than as a )8-elimination (6) which is associated with a H/D eflFect of 5.5. This is larger than observed in normal 1,2-hydride shift reactions. We presently favor the view that the migrating hydrogen attains a greater degree of hydride ion character in the transition state than in conventional 1,2-hydride shift reactions (this schematically indicated by the dotted lines in Figure 13). 

Palladium-catalyzed reactions have been widely investigated and have become an indispensable synthetic tool for constructing carbon-carbon and carbon-heteroatom bonds in organic synthesis. Especially, the Tsuji-Trost reaction and palladium(II)-catalyzed cyclization reaction are representative of palladium-catalyzed reactions. These reactions are based on the electrophilic nature of palladium intermediates, such as n-allylpalladium and (Ti-alkyne)palladium complexes. Recently, it has been revealed that certain palladium intermediates, such as bis-7i-allylpalladium, vinylpalladium, and arylpalladium, act as a nucleophile and react with electron-deficient carbon-heteroatom and carbon-carbon multiple bonds [1]. Palladium-catalyzed nucleophilic reactions are classified into three categories as shown in Scheme 1 (a) nucleophilic and amphiphilic reactions of bis-n-allylpalladium, (b) nucleophilic reactions of allylmetals, which are catalytically generated from n-allylpalladium, with carbon-heteroatom double bonds, and (c) nucleophilic reaction of vinyl- and arylpalladium with carbon-heteroatom multiple bonds. According to this classification, recent developments of palladium-catalyzed nucleophilic reactions are described in this chapter. 

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