Fragmentation alkyl halides

When an ester enolate reacts with an aldehyde or a ketone, the product is a hydroxy-ester. This disconnection is shown for both partners. If the reaction is turned around, the reaction of an enolate derived from an aldehyde or a ketone and then with an ester gives a keto-aldehyde or a diketone. Both disconnections are shown. The enolate alkylation reaction involves disconnection of an alkyl halide fragment from an aldehyde, ketone, or ester. In addition, the malonic acid and acetoacetic acid syntheses have unique disconnections. 

Having gamed one electron the alkyl halide is now negatively chaiged and has an odd numbei of elections It is an anion radical The extra electron occupies an antibondmg oibital This anion radical fragments to an alkyl radical and a halide anion... 

Note This reaction involves a polar acidic mechanism, not a free-radical mechanism It is a Friedel-Crafts alkylation, with the slight variation that the requisite carbocation is made by protonation of an alkene instead of ionization of an alkyl halide. Protonation of C4 gives a C3 carbocation. Addition to Cl and fragmentation gives the product. 

The gaseous dichlorocarbene radical cation reacted with alkyl halides via a fast electrophilic addition to form a covalently bonded intermediate (CI2C—X—R)+ in a Fourier transform ion cyclotron resonance mass spectrometer. This intermediate fragments either homolytically or heterolytically to produce net halogen atom or halogen ion transfer product. Addition of carbonyls to the carbene ion is followed by homolytic cleavage of the C-O bond to yield a new carbene radical cation. 

The metalation chemistry of the imidazoline system has received attention only recently, with the lithiation of l-benzyl-2-imidazoline being found to occur at the 2-position (90TL1767). Although the reactivity of the lithi-ated species with alkyl halides was poor, better results were achieved with disulfide and carbonyl electrophiles (90TL1767,90TL1771). The products formed by reaction with ketones were found to be unstable with respect to fragmentation, and this result was utilized to provide a new route for the synthesis of unsymmetric ketones (Scheme 138). 

Peptidomimetics in which one amide bond is replaced by a phosphinic acid (R-P(0H)(=0)-R phosphinic peptides ) are of interest as potential protease inhibitors [17-19]. These compounds have been prepared either from orthogonally protected phosphorus-containing monomers [17,18,20], or by forming the phosphorus-containing fragments on solid phase, as sketched in Figure 11.4 [19,21], Phosphinic acids have been prepared on solid phase mainly by reaction of carbon electrophiles with monoalkylphosphinates. As carbon electrophiles, acrylates, aldehydes, reactive alkyl halides, or a, 3-unsaturated ketones can be used. 

Aryl and Alkyl Halides. Although the factors governing photodissociation of alkyl halides are not well known, there exists clear experimental evidence for electron exchange between the radical fragments formed by C-X homolysis. For example, the ultraviolet photolysis of 1-octyliodide shows photorearrangement to the 2-halogenated isomer, eq. 58 (181) ... 

Notice that for SN2 substitution, the alkyl halide came from the less sterically hindered group. For SN1 type reactions, the alkyl halide forms from the fragment of the original molecule that forms the more stable cation. Thus, the reaction of t-butyl ethyl ether with HI gives t-butyl iodide and ethyl alcohol. The following mechanism occurs ... 

The cofragmentation of a benzylic radical cation and a fragmentable radical anion, such as that of alkyl halides, is another way of obtaining an efficient process [191-193] (Sch. 10). 

For non-activated haloalkanes, a dissociative electron capture7,15,28 has been proposed mainly based on theoretical calculations and experimental findings in the gas phase, solid matrices and electrochemistry in polar solvents. The ET to the halide is accompanied by bond fragmentation and therefore radical anion intermediates are not formed. However, this is not necessarily the case for bridgehead alkyl halides. For these compounds, in which... 

OxazoIones are alkylated at position 4 by alkyl halides, allyl halides and electrophilic alkynes, such as methyl propiolate (equation 36). In contrast, 2-phenyloxazolones react with methyl vinyl ketone at both C(4) and C(2) to yield a mixture of Michael adducts (equation 37). If the phenyl substituent is replaced by the bulky 2,4,6-trimethylphenyl group the addition is directed exclusively to C(4) (81CB2580). Alkylation of 5(4//)-oxazolones is a key step in the synthesis of ketones from a-amino acids (Scheme 16). The outcome of this sequence is the union of the electrophilic fragment R3 with the group R2CO the amino acid thus functions as the equivalent of an acyl anion (78AG(E)450). 

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