Nucleophilic reactions heteroatoms

Reaction of Heteroatom Nucleophiles. Reaction of A -tetraethylthiourea with nitrated -(trifluoromethyl)-diarylsulfonium salt proceeds smoothly without a base to provide a 5 -trifluoromethylated compound (eq 13). Sodium sulfinate readily converts into the corresponding aryl triflone in 81% yield (eq 14). Trivalent phosphorus compounds are also viable electrophiles in the electrophihc trifluoromethylation reaction, providing diethoxytrifluoromethylphosphonate with 70% yield (eq 15). 

Conjugate Addition of Heteroatom Nucleophiles and Subsequent Nef Reaction... 

Ring-opening with heteroatomic nucleophiles is certainly among the most thoroughly studied behavior of epoxides, and this reaction continues to be a versatile workhorse of synthetic utility. This is exemplified in the recent literature by the examples of the p-cyclodextrin-catalyzed aminolysis of simple epoxides by aniline derivatives (i.e., 53 - 54) <00SL339> and the synthesis of oxa-azacrown ethers through the treatment of Ws-epoxides 55 with diamines 56. Yields in the latter synthesis are sensitive to the size of the macrocycle and substitution on the bis-epoxide <00TL1019>. 

A review of the reaction of nitroalkanes RNO2 with carbon and heteroatom nucleophiles X to yield RX has appeared438. The nucleophilic displacement of a nitro group in benzylic and tertiary nitroalkanes by a thiophenyl group is exemplified in equation 130439. 

The regio- and diastereoselective rhodium-catalyzed sequential process, involving allylic alkylation of a stabilized carbon or heteroatom nucleophile 51, followed by a PK reaction, utilizing a single catalyst was also described (Scheme 11.14). Alkylation of an allylic carbonate 53 was accomplished in a regioselective manner at 30 °C using a j-acidic rhodium(I) catalyst under 1 atm CO. The resulting product 54 was then subjected in situ to an elevated reaction temperature to facilitate the PK transformation. 

The electrophile-induced cyclization of heteroatom nucleophiles onto an adjacent alkene function is a common strategy in heterocycle synthesis (319,320) and has been extended to electrophile-assisted nitrone generation (Scheme 1.62). The formation of a cyclic cationic species 296 from the reaction of an electrophile (E ), such as a halogen, with an alkene is well known and can be used to N-alkylate an oxime and so generate a nitrone (297). Thus, electrophile-promoted oxime-alkene reactions can occur at room temperature rather than under thermolysis as is common with 1,3-APT reactions. The induction of the addition of oximes to alkenes has been performed in an intramolecular sense with A-bromosuccinimide (NBS) (321-323), A-iodosuccinimide (NIS) (321), h (321,322), and ICl (321) for subsequent cycloaddition reactions of the cyclic nitrones with alkenes and alkynes. 

Reaction of nucleophiles with the polarized N=C bond of azines proceeds via dearomatization and formation of the corresponding 1,2-adduct. With alkyllithiums, for example, it is possible to isolate the dihydro products by careful neutralization of the reaction mixtures these are, in general, rather unstable, however, and can easily be reoxidized to the fully aromatic compounds (Scheme 4). The dihydro adducts formed in these direct nucleophilic addition reactions can also be utilized for the introduction of substituent groups /3 to the heteroatom. Thus, reaction of (35) with one of a number of electrophiles, followed by oxidation of the intermediate dihydro product, constitutes a simple and, in many cases, effective method for the introduction of substituent groups at both the 2- and 5-positions of the pyridine ring (Scheme 4). Use of LAH in this sequence, of course, results in the formation of 3-substituted pyridines. 

Because of their high reactivity, these complex salts react rapidly and regiospecifically, at low temperature, with a number of carbon and heteroatomic nucleophiles, including thiols, amines, and alcohols. Finally, exposure of the double bond takes place under particularly mild conditions so that isomerization of the (3,Y-unsaturated carbonyl system may be avoided. The present scope of reactions with these vinyl cation synthons is summarized in [able I. 

Typically, low temperatures are necessary to suppress these reactions. Additionally, other considerations, such as stabilization of the propagating centers, use of additives to suppress ion-pair dissociation and undesirable protic initiation, and the use of high purity reagents to prevent the deactivation of the carbenium by heteroatomic nucleophiles are often required. However, by careful... 

The major focus in this chapter will be on synthesis, with emphasis placed on more recent applications, particularly those where regiochemistry and stereochemistry are precisely controlled. The reader is referred to the earlier reviews for full mechanistic information and details of historic interest. Electrophilic addition of X—Y to an alkene, where X is the electrophile, gives products with functionality Y (3 to the heteroatom X. Further transformations of X and/or Y provide the basis for diverse synthetic applications. These transformations include replacement of Y by hydrogen, elimination to form a ir-bond (either including the carbon bonded to X or (3 to that carbon so that X is now in an allylic position), and nucleophilic or radical substitution. Representative examples of these synthetic methods will be given below. This chapter will include examples of heterocycles formed in one-pot reactions where the the initial alkene-electrophile adduct contains an electrophilic group that can react further. Examples of heterocycles formed in several steps from alkene-electrophile adducts will also be considered. Cases in which activation by an external electrophile directly results in addition of an internal heteroatom nucleophile are treated in Chapter 1.9 of this volume. 

This chapter on electrophilic heteroatom cyclizations covers reactions of carbon-carbon ir-bonds in which activation by an external electrophilic reagent results in addition of an internal heteroatom nucleophile. The general reaction is illustrated in Scheme 1. These cyclization reactions generate heterocyclic products, but many synthetic applications involve subsequent cleavage of the newly formed heterocyclic ring. 

The identity of the heteroatom present in a target molecule dictates the identity of the nucleophilic atom (Z) to be used in an electrophilic heteroatom cyclization reaction of the type shown in Scheme 1. However, successful application of this strategy to the synthesis of specific target molecules also requires selection of appropriate combinations of nucleophilic functionality (Z-R) and activating electrophile. Therefore, major subdivisions within this chapter are based on the identity of the heteroatom, although comparisons between results observed for the different heteroatoms will be made. 

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