Electrophiles synthesis

Cyclocarbamation Induced by Electrophiles Synthesis of 2-Oxazolidinones and Tetrahydro-2//-1,3-oxazin-2-ones... 

Eskola, O., Gronroos, T., Bergman, J., et al. (2004) A novel electrophilic synthesis and evaluation of medium specific radioactivity (lR,2S)-4-[18F]fluorometaraminol, a tracer for the assessment of cardiac sympathetic never integrity with PET. Nucl. Med. Biol., 31, 103-110. 

Hojo, M., Harada, H. and Hosomi, A. 1994. A novel and efficient generation of functionalized vinylcopper reagents and their reactions with electrophiles Synthesis of P-methylthiobntenolides. Chem. Lett. 3 437-440. 

Oxidative phosphorylation produces reactive oxygen species (Watkins, 1999). These are deactivated by antioxidants present within the mitochondrion. GSH is present within mitochondria as a scavenger for peroxides and electrophiles. Synthesis of GSH requires ATP... 

Memorization Task 16.5 Lithium and Grignard reagents react well with C=0 electrophiles Synthesis Tip 3 There are two main types of carbon electrophiles, Z2C=0 and RsC—X... 

Ishiyama T, Mori M, Suzuki A, Miyaura N. The palladium-catalyzed cross-coupling reaction of 9-organothio-9-borabicyclo[3.3.1]nonanes with organic electrophiles synthesis of unsymmetrical sulfides. J. Org. Chem. 1996 525 225-231. 

Reactive electrophiles used in synthesis, e g. RCH2COCI plus (CIjC NMeir, gives (Me N)C1C = C(R)COCl. 

Synthesis Only cyclohexanone can enolise, but the a-diketone is more electrophilic no control needed ... 

Synthesis No control is need because only the ketoacid can enolise and the aldehyde is more electrophilic. TM 89 is formed in 80% yield when the two starting materials are mixed in MeOH with KOH at room temperature tHelv. Chim. Acta. 1931,14, 783). 

Synthesis Control will be needed in the condensation as the ketone C is more reacfiye than the acid D both in enolisation and electrophilic power. The Reformatsky looks a good method. Again we don t know how this commercial product is actually made ... 

Synthesis Since a-halo-carbonyl compounds are very reactive electrophiles, we can use a short cut ... 

The first reaction was involved in a synthesis of morphine, the starting ketone being made by reduction of a substituted naphthalene O. Amer. Chem. Soc., 1950, 72, 3704). No doubt an epoxide could have been used as the electrophile. 

The next example uses another carbon electrophile how can you use the relationship of the two functional groups in TM 249 to design a synthesis of the molecule ... 

You will have noticed that, throughout this chapter, the heteroatom has always been hie nucleophile. There is one way to use nitrogen as an electrophile however and this provides a good synhion for ammo acid synthesis ... 

One of the most versatile methods for the synthesis of derivatives with the acetylene or cumulene system consists In deprotonatlon of the starting acetylene or cumulene and subsequent reaction of the anionic or organometal1ic intermediate with an electrophilic reagent. 

The synthesis of spiro compounds from ketones and methoxyethynyl propenyl ketone exemplifies some regioselectivities of the Michael addition. The electrophilic triple bond is attacked first, next comes the 1-propenyl group. The conjugated keto group is usually least reactive. The ethynyl starting material has been obtained from the addition of the methoxyethynyl anion to the carbonyl group of crotonaldehyde (G. Stork, 1962 B, 1964A). 

A completely different, important type of synthesis, which was developed more recently, takes advantage of the electrophilicity of nitrogen-containing 1,3-dipolar compounds rather than the nucleophilicity of amines or enamines. Such compounds add to multiple bonds, e.g. C—C, C C, C—O, in a [2 + 3 -cycioaddition to form five-membered heterocycles. 

Application of 7r-allylpalladium chemistry to organic synthesis has made remarkable progress[l]. As deseribed in Chapter 3, Seetion 3, Tt-allylpalladium complexes react with soft carbon nucleophiles such as maionates, /3-keto esters, and enamines in DMSO to form earbon-carbon bonds[2, 3], The characteristie feature of this reaction is that whereas organometallic reagents are eonsidered to be nucleophilic and react with electrophiles, typieally earbonyl eompounds, Tt-allylpalladium complexes are electrophilie and reaet with nucleophiles such as active methylene compounds, and Pd(0) is formed after the reaction. 

Another variation of the Madelung synthesis involves use of an O-alkyl or O-silyl imidate as the C2 electrophile. The mechanistic advantage of this modification stems from avoiding competing N-deprotonation, which presumably reduces the electrophilicity of the amide group under the classical conditions. Examples of this approach to date appear to have been limited to reactants with a EW substituent at the o-alkyl group[15,16]. 

Retrosynthetic path b in Scheme 3.1 corresponds to reversal of the electrophilic and nucleophilic components with respect to the Madelung synthesis and identifies o-acyl-iV-alkylanilines as potential indole precursors. The known examples require an aryl or EW group on the iV-alkyl substituent and these substituents are presumably required to facilitate deprotonation in the condensation. The preparation of these starting materials usually involves iV-alkyla-tion of an o-acylaniline. Table 3.3 gives some examples of this synthesis. 

Donor substituents on the vinyl group further enhance reactivity towards electrophilic dienophiles. Equations 8.6 and 8.7 illustrate the use of such functionalized vinylpyrroles in indole synthesis[2,3]. In both of these examples, the use of acetyleneic dienophiles leads to fully aromatic products. Evidently this must occur as the result of oxidation by atmospheric oxygen. With vinylpyrrole 8.6A, adducts were also isolated from dienophiles such as methyl acrylate, dimethyl maleate, dimethyl fumarate, acrolein, acrylonitrile, maleic anhydride, W-methylmaleimide and naphthoquinone. These tetrahydroindole adducts could be aromatized with DDQ, although the overall yields were modest[3]. 

Directed thallation has been useful for synthesis of some 4- and 7-substituted indoles. Electrophilic thallation directed by 3-substituents is a potential route to 4-substituled indoles. 3-Formyl[7], 3-acetyi[8] and 3-ethoxycarbonyl[7] groups can all promote 4-thallation. 1-Acetylindoline is the preferred starting... 

Sometimes the orientation of two substituents m an aromatic compound precludes Its straightforward synthesis m Chloroethylbenzene for example has two ortho para directing groups m a meta relationship and so can t be prepared either from chloroben zene or ethylbenzene In cases such as this we couple electrophilic aromatic substitution with functional group manipulation to produce the desired compound... 

Isoprene has sometimes been used as a starting matenal in the laboratory synthesis of ter penes In one such synthesis the first step is the electrophilic addition of 2 moles of hydrogen bromide to isoprene to give 1 3 dibromo 3 methylbutane... 

These compounds perform a dual function in synthesis procedures. The introduction of a complex anion assists in the stabilization of the desired product and the generation of unique intermediates by chloride displacement, eg, silver hexafluorophosphate, AgPF, forms adducts with neutral diamagnetic organometaHics which can act as controUed sources of highly reactive cations (29). Silver hexafluoroantimonate, AgSbF, is an electrophilic... 

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

However, the vast majority of research has been devoted to synthesis involving electrophilic substitution on the aromatic ring of hydroquinone. Hence, phenylhydroquinone can be obtained by the reaction of phenyl dia onium salts (18) with hydroquinone (82). 

Reaction with Halogen Electrophiles. The synthesis of l-haloa2iridines, which are prone to explosion, has been carried out using hypohahtes (290,291). l-Chloroa2iridine [10165-13-6] produced in this way reacts with l-Hthiated ethyleneimine to give l,l -dia2iridine [4388-03-8]. Perchloryla2iridine [112405-46-6] has been prepared by reaction of ethyleneimine with dichlorine heptoxide at —20° C (292). 

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