Alkyl anion synthons reagents

Although this method is not a general procedure, being specific for a-nitroketones, it has several merits to avoid the use of toxic reagents such as organotin compounds. Functionalized ketones have been prepared by this denitration reaction, in which functionalized nitroalkanes are used as alkyl anion synthons. For example, 3-nitropropanal ethylene acetal can be used as synthon of the 3-oxo-propyl anion and 1,4-dicarbonyl compounds are prepared, as shown in Eq. 7.88.135... 

Ballini, R. and Rosini, G. 1988. Functionalized nitroalkanes as useful reagents for alkyl anion synthons. Synthesis, 11 833 7. 

A C—N disconnection of a primary amine gives rise to the carbocation and amide anion synthons. It might be predicted therefore that treatment of an alkyl halide with ammonia (reagents equivalent to the above synthons) under pressure would constitute a suitable synthesis of a primary amine. In practice, however, the yield is poor since a mixture of all three classes of amines, together with some of the quaternary ammonium salt, is obtained, owing to more ready further alkylation of the sequentially formed products. 

An alternative reagent equivalent for the amide anion synthon is the potassium salt of phthalimide which can only react with one molecular proportion of alkyl halide. The resulting JV-alkylphthalimide is then cleaved to the primary amine (the Gabriel synthesis). The preliminary preparation of potassium phthalimide (from a solution of phthalimide in absolute ethanol and potassium hydroxide in 75% ethanol) may be avoided in some cases by boiling phthalimide with the halide in the presence of anhydrous potassium carbonate. The cleavage of the JV-substituted phthalimide is best effected by reaction with hydrazine hydrate and then heating the reaction mixture with hydrochloric acid. The insoluble phthalylhydrazide is filtered off, leaving the amine hydrochloride in solution from which the amine may be liberated and isolated in the appropriate manner. 

A sequence in which a carbonyl group has been masked as a sulfur derivative, alkylated with an electrophile, and then revealed again is a nucleophilic acylation. These nucleophilic equivalents of carbonyl compounds are known as acyl anion equivalents. In the retrosynthetic terms of Chapter 50 they are d1 reagents corresponding to the acyl anion synthon. 

Ketones. The reagent (1) is a propenoyl anion synthon. After alkylation, enones are released. On the other hand, the adducts undergo allylic displacement with Grignard reagents, and on hydrolytic workup, ketones are formed. The possibility of creating a-bromoalkyl ketones, 1,4-diketones, 2-ethoxy-2-cyclopentenones, and a-keto enamines bespeaks for the versatility of this synthesis. 

Alkyl-substituted allylmetals 1 usually cover the synthon A. Since oxidative cleavage of the C-C double bond in the products formed can be readily achieved, such reagents are often used as equivalents for the appropriate cnolatc synthons B and C or /1-hydroxycarbonyl anions D. Subsequent hydroboration extends their scope on y-hydroxyalkyl anions E. 

More usually, none of the substituents gives a stable anion and so we use the synthetic equivalent of the anion - the Grignard reagent or alkyl lithium. - We refer to "Et" " as a SYNTHON for which BtMgBr is the synthetic equivalent. 

Tosylmethyl isocyanide (TosMIC) (75 R = H), a versatile reagent in synthesis, can also be used as an acyl anion equivalent. For instance symmetrical and unsymmetrical diketones were prepared by using this TosMIC synthon (equation 40). Ketones are homologated to enones by alkylating the condensation product derived from TosMIC, followed by acid hydrolysis (Scheme 46). 1-Isocyano-l-tosyl-l-alkenes (76), formed by the reaction of TosMIC with an aldehyde or ketone, react with a primary amine or ammonia to give 1,5-disubstituted (or 5-monosubstituted) imidazoles in high yield (Scheme 47). ... 

Strategy d(ii) (see 4d) follows logically as similar methods are involved. The same enone 74 can be made by this strategy 74b if an acyl anion equivalent (a d1 reagent) for the synthon 79 can be alkylated at the carbon atom of the carbonyl group. 

Disconnection 4a to an enone 5 is still possible, but we should have to add a d1 reagent, or acyl anion equivalent 6 instead of an enolate. At the time of Stork s work, there were no d1 reagents which reliably added Michael fashion, so he invented one. It would obviously be convenient if the d1 reagent would also act as an alkylating agent in the synthesis of 6, that is if it would act as the doubly nucleophilic synthon 7. 

Alkylation of primary nitro compounds (23) is a simple way to make secondary nitro compounds. In this sequence, the starting material (23) has latent carbonyl functionality so that its anion is a reagent for the synthon R C0 —it is an acyl anion equivalent. We shall need this type of synthon in the next few chapters. 

The procedure for oxidation of the sulfide to the sulfone is based on that reported earlier by Bordwell and Pitt. The synthetic utility of phenyl vinyl sulfone and sulfoxide derives not only from their ability to serve as excellent Michael acceptors toward such reagents as enolate anions and organometallics, but also as moderately reactive dienophiles in Diels-Alder reactions. " The resulting adducts, in turn, can be chemically modified so that these electron-deficient olefins serve as useful synthons for acetylene,ethylene,terminal olefins,vinylsilanes, and ketene in [4 + 2] cycloadditions. Phenyl vinyl sulfone undergoes ready cycloaddition to Danishefsky s diene in the first step of a protocol for the regiospecific y-alkylation of 2-cyclohexenones. Furthermore, the ready lithiation of phenyl... 

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