Heteroatom-centered nucleophiles

Addition ofN-, S- and P-Nucleophiles The reaction of nitrones with heteroatom centered nucleophiles has been little investigated and are mainly applied to the synthesis of new heterocyclic systems and stable nitroxyl radicals, containing a heteroatom at the a-carbon atom. 

The addition of anionic heteroatom-centered nucleophiles (HO, MeO, pyr-azolate, etc.) and carbanions (CN , enolates, aUcyl or alkynyl reagents) to the cationic allenylidenes [Ru( 7 -C9H7)(=C=C=CR R )(PPh3)2][PF6] [125-128,... 

Propargylic Substitution Reactions with Heteroatom-Centered Nucleophiles... 

In the presence of a catalytic amount of methanethiolate-bridged diruthenium complex (la abbreviated as met-DIRUX), reactions of propargylic alcohols (2) with a variety of heteroatom-centered nucleophiles such as alcohols, thiols, amines, amides, and diphenylphosphine oxide gave the corresponding propargylic substituted... 

Scheme 7.5 Propargylic substitution reactions of propargylic alcohols with a variety of heteroatom-centered nucleophiles.

Hundreds of carbon- and heteroatom-centered nucleophilic agents have been involved in Sn reactions, which proved to be both a convenient and powerful synthetic tool for applicatimi in heterocyclic and medicinal chemistry, polymer chemistry, and other branches of chemistiy. It should be noted, however, that C-nucleophiles are still prevailing in the Sn reactimis over heteroatom-centered ones because of the following reasons (1) the C-C bond formation is one of the main of tasks of organic synthesis (2) as a rule, the C-adducts are more stable in comparison with the o -adducts derived from additimi of heteroatom-centered nucleophiles to the same aromatic substrates. 

Various carbon- and heteroatom-centered nucleophiles have been successfully used in the SrnI arylation. Hence, carbanions readily obtained by deprotonation can be employed as nucleophiles. The reaction with phenolates leads to the formation of carbon-carbon bonds (ortho-arylation) [5], while aryl-heteroatom bond formation occurs when using Sn, P, As, Sb, S, Se and Te-centered anions. SrnI reactions are not sensitive to steric hindrance, and good yields are usually obtained for ortho-substituted aryl radicals [6]. Many functional groups such as OR, SAr, CF3, NH2, SO2R and CN are tolerated however, the niho group as aryl substituent leads to chain termination [7]. 

Many heteroatom-centered nucleophiles can be arylated by the SrnI mechanism. For example, Ar-Cl and NMesAr react with MesSn" in liquid ammonia to provide the corresponding stannylated arenes in high yields [16,17]. Di- and tri-stannylated aromatic compounds can be prepared using di- and tri-chlorobenzenes as radical precursors [16]. The fact that Ar-Cl reacts easily with MesSn" by SsNl-typs chemistry and that Ar-1 bonds are much more reactive than Ar-Cl bonds in the Stille reaction allowed for the development of an attractive iterative approach to the synthesis of poly-aryl compounds, as shown in Scheme 13.2. 

Whereas the earher examples about anionic cychzation reactions refer to heteroatom-centered nucleophiles, the formation and cychzation of aryne-tethered oiganohthiums have been independently explored by Bailey and Sanz and involves the formation of a new C—C bond in the cychzation step... 

Different carbon- or heteroatom-centered nucleophilic positions a-bonded to a suitable electrophilic functionality can undergo facile cleavage by adding to arynes and by further intramolecular nucleophilic substitution in the initially formed aryl anion or zwitterion intermediate. The overall process results in the insertion of an aryne into a nucleophilic-electrophilic o-bond. 

The design of this new class of trifluoromethylation reagents led to the development of a vast number of specific methodologies addressing a broad array of organic nucleophilic substrates. These cover heteroatom-centered nucleophiles such as thiols, phosphines, alcohols, and azoles, as well as carbon-centered nucleophiles in their virtually unlimited diversity. The formation of the new X-CF3 or C-CF3 bond relies on several different strategies as discussed below, in what is intended to be a brief overview. A more exhaustive account has recently appeared in the form of a comprehensive review article [2]. 

On using enamine activation, nucleophiles were limited to aldehydes and ketones but the emergence of H-bonding activation [31] has expanded considerably this scope. With this mode of activation other carbon-centered nucleophiles and also heteroatom-centered nucleophiles could be considered. During the period 2003-2012, growing interest was focused on the ability to perform catalytic enantioselechve reactions with small organic molecules able to produce such weak interachons. 

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