Polar addition nucleophilic

The first three chapters discuss fundamental bonding theory, stereochemistry, and conformation, respectively. Chapter 4 discusses the means of study and description of reaction mechanisms. Chapter 9 focuses on aromaticity and aromatic stabilization and can be used at an earlier stage of a course if an instructor desires to do so. The other chapters discuss specific mechanistic types, including nucleophilic substitution, polar additions and eliminations, carbon acids and enolates, carbonyl chemistry, aromatic substitution, concerted reactions, free-radical reactions, and photochemistry. 

The exact behavior and mechanism of electrophilic additions to alkynes is clearly strongly dependent upon the reaction conditions. In a highly polar and strongly acidic but weakly nucleophilic solvent such as trifluoroacetic acid, addition via a vinyl cation intermediate is favored whereas in less polar, more nucleophilic solvents such as acetic acid, a different mechanism prevails. 

A solvent-dependent chemoselectivity, pointing to a dependence of the relative reactivities of the 1,2- and 1,1-disubstituted double bonds on solvent polarity and nucleophilicity, has been observed in the reaction of benzeneselenenyl chloride with 2-methylenebicyclo[2.2.1]hept-5-ene (159) which gives products 160-163140. In methylene chloride the reaction occurs with a moderate chemoselectivity, attack on the endocyclic bond being preferred over that on the exocyclic one in a 60 40 ratio. In methanol, the addition is completely chemoselective and the attack occurs exclusively on the endocyclic double bond (equation 132). It may be further noted that 162 and 163 isomerize and solvolyze at high temperatures, leading to the homoallylic products 160 and 161. 

The addition of RLi and other nucleophiles to carbonyl functions in general proceeds via one of the two possible reaction pathways, polar addition (PL) and electron transfer (ET)-radical coupling (RC) sequence (equation 5). Current reaction design for the synthetic purpose of additions of common nucleophiles to aldehydes and ketones is mostly based on the polar mechanism, but apparently the ET process is involved in some reactions of, for example, Grignard reagents Mechanistically there are three possible variations the PL pathway, the ET rate-determining ET-RC route and the RC rate-determining ET-RC route. 

In addition to the choice of Lewis acid, added common ion salt, and temperature, the fast equilibrium between active and dormant species can be fostered by including additional nucleophiles (separate from the nucleophilic counterion) in the reaction system and by variations in solvent polarity. Nucleophiles act by further driving of the dynamic equilibrium toward the covalent species and/or decreasing the reactivity of ion pairs. Nucleophilic counterions and added nucleophiles work best in nonpolar solvents such as toluene and hexane. Their action in polar solvents is weaker because the polar solvents interact with the nucleophiles and nucleophilic counterions, as well as the ion pairs. Polar solvents such as methylene... 

The use of solvents more polar and nucleophilic than benzene, e.g. ethanol, increases the electrophilicity of the sterically more-accessible position 3 because of the interaction of the cation with the solvent, and the addition of primary amines occurs in position 1. Thus, one may conclude that decarboxylation of salts 62 in the reaction with primary amines occurs by a preliminary addition of nucleophile, whereas the decarboxylation of isoquinolinium salts 161 to 162 proceeds by a ylide mechanism as is shown here. As known, the latter pathway requires the use of stronger bases and more elevated temperatures (79MI3). 

Haloamines and other precursors to aziridines can be generated by various polar additions . Three important groups of polar processes leading to aziridines are shown in Scheme 22. In the aza-Darzens route , the imine acts as an electrophile at carbon and later as a nucleophile at nitrogen, while the -haloenolate acts initially as a nucleophile at carbon and later as an electrophile at the same carbon. The roles of the two components are reversed for the polar aziridination route, which is related to the epoxidation reaction. In the -haloenone route, the 1,2-dihalide or -haloenone acts formally as a bis-electrophile while the amine acts as a bis-nucleophile. 

With CF3C=CCF3 or olefins with an internal double bond such as cis- or fraras-F-2-pentene, F-cyclobutene, or l,2-dichloro-l,2-difluoro-ethylene, or with a geminally disubstituted olefin such as 1,1-dichloro-2,2-difluoroethylene, only fully fluorinated products were obtained, likely through a nucleophilic fluorination mechanism. This fact, plus the necessity for a Lewis acid catalyst for addition to proceed, is evidence for an electrophilic addition mechanism. Others have suggested polar addition of BF3 to the olefin with RfBF2 as a reactive intermediate (294). 

Azodicarboxylates are recognized for their ability to participate as 2ir components of HOMOdi e-con-trolled Diels-Alder reactions with dienes and for their participation in ene reactions with reactive al-kenes. 489 j, addition, electron-rich or reactive simple alkenes that do not contain a reactive allylic hydrogen atom have been shown to participate in competitive [2 + 2] and [4 + 2] cycloaddition reactions with azodicarboxylates in which the observed course of the reaction is dependent upon the solvent polarity and nucleophilic character of the alkene (Table 13). As may be anticipated, alkoxycarbonyl-aroyldiimides (4), diaroyldiimides (5), and aiylaroyldiimides (6) participate with increasing selectivity as 4tr components of [4 + 2] cycloaddition reactions. 

There is no doubt that the solvent plays an important role in process (1). It seems to be accepted that activation energy for charge separation should be reduced with increasing polarity Various nucleophiles, e.g. SCN , I, MeO, amines, etc., do, in fact, react faster in polar than in non-polar solvents Eliminations, the microscopic reverse of additions, take the syn path more often in non-polar or associating solvents . All of this is supportive of the idea that polar solvents favour anti attack, other things being equal. 

Singlet photosensitized polar addition of methanol to (A )-(>)-limonene (102) in nonpolar solvents afforded a mixture of the diastereomeric ethers 103 and 104 and the rearrangement product 105 (Scheme 6.42).677 The diastereomeric excess (de) of the photoadduct was optimized by varying the solvent polarity, reaction temperature and nature of the sensitizer. The first step of the reaction is the Z E photoisomerization (Section 6.1.1) of 102 to a highly strained /i-isomer, followed by protonation and methanol addition. The initial formation of a carbocation via the protonation step has been excluded under those reaction conditions. The Markovnikov-oriented methanol attack on the less-hindered (Rp)-(E)-102 compared with that of (Sp)-(E)-U)2 explains why 103 can be obtained in up to 96% de upon sensitization with methyl benzoate in a methanol solution. The hypothesis that Z E isomerization of the cyclohexene moiety affords a strained (reactive) alkene, whereas isomerization of the exocyclic double bond does not, was supported by the observation of an exclusive nucleophilic addition to the cyclohexene double bond. 

The reactions of HTIB with alkenes (Scheme 3.73) can be rationalized by a polar addition-substitution mechanism similar to the one shown in Scheme 3.70. The first step in this mechanism involves electrophilic flnfi-addition of the reagent to the double bond and the second step is nucleophilic substitution of the iodonium fragment by tosylate anion with inversion of configuration. Such a polar mechanism also explains the skeletal rearrangements in the reactions of HTIB with polycyclic alkenes [227], the participation of external nucleophiles [228] and the intramolecular participation of a nucleophilic functional group with the formation of lactones and other cyclic products [229-231]. An analogous reactivity pattern is also typical of [hydroxy(methanesulfonyloxy)iodo]benzene [232] and other [hydroxy(organosulfonyloxy)iodo]arenes. 

Although the vast majority of stepwise polar additions to ortho-benzyne involve nucleophilic attack on the aryne, electrophilic attack is also possible provided that the aryne is generated by a method that does not involve strongly basic conditions. Few such additions are synthetically useful, with the exception of the formation of 1,2-dihalobenzenes by reactions of ortho-benzynes with halogens, although alternative mechanisms initiated by nucleophilic attack of halide may be envisaged. Radical reactions of ortHo-benzyne, on the other hand, are extremely rare. 

In addition to polarity and nucleophilicity toward the bromonium ion, other solvent properties may come into play. The rate-limiting step in electrophilic bromine addition is thought to be the conversion of a CT complex to a cation-bromide ion pair, which is consistent with the observation that the rate constant for bromine addition increases as solvent polarity increases. Solvent may also electrophilically assist the removal of the bromide ion from the alkene-Br2 CT complex by hydrogen bonding to a developing bromide ion (Figure 9.6). It has been estimated that this electrophilic solvent participation can lower the energy of bromonium ion formation by 60 kcal/mol. ° Additional support for the role of electrophilic... 

Let us now consider the mechanism of polar addition to a carbon-carbon double bond, specifically the addition of acids to alkenes. The carbon-carbon double bond, because of its pi electrons, is a nucleophile. The proton (H ) is the attacking electrophile. As the proton approaches the pi bond, the two pi electrons are used to form a sigma bond between the proton and one of the two carbon atoms. Because this bond uses both pi electrons, the other carbon acquires a positive charge, producing a carbocation. 

The first characteristic reaction of arynes to be discovered was the addition of polar species, especially nucleophiles, to the triple bond. Since arynes are bidentate intermediates, such additions could lead to two different products in the event of unsymmetrical substitution in the aryne ring. If, as is often the case for such polar additions, the aryne was generated by elimination of HX from a monosubstituted aromatic compound 126, then the product 127 with the entering group in the position previously occupied by the substituent is called the product of normal or ipso-substitution while the rearranged product 128 is referred to as that of cine-substitution. Should the aryne be generated from the isomeric precursor 129 then the designation of which is the normal... 

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