1.7?-Eliminations heteroatoms from substrate

Reactions in which two atoms or atom groups X and Y are removed from a compound are referred to as eliminations (Figure 4.1). In many eliminations X and Y are removed in such a way that they do not become constituents of one and the same molecule. In other eliminations they become attached to one another such that they leave as a molecule of type X—Y or X=Y or as N=N. The atoms or groups X and Y can be bound to C atoms and/or to heteroatoms in the substrate. These atoms can be sp3 or sp2 hybridized. 

The facile elimination of -heterosubstituents in ketones allows for the ready construction of a,p-enones. Three different heteroatoms have been employed, chlorine, nitrogen and oxygen. The -chloro enones (products of Friedel-Crafts acylation) suffer Nazarov cyclization under standard conditions. -" Jacquier has prepared a series of -amino enones (31) from Mannich condensations." These substrates undergo cyclization in modest yields under standard conditions (equation 23). Takeda has found that the readily available" tetrahydro-4-pyranones (32) produce 2-cyclopentenone-4-carboxylates upon treatment with TMS-I (equation 24). " It is noteworthy that the putative a-carboalkoxy divinyl ketones have been independently cyclized by Marino using TMS-I. ... 

The pioneering studies in this area were reported in 1999 by Narasaka, who demonstrated intramolecular heteroatom Heck-type reactions of 0-pentafluorobenzoyl oximes [97]. As shown below, treatment of unsaturated substrate 97 with a catalytic amount of Pd(PPh,y in the presence of triethyl amine provided pyrrole 98 upon workup with chlorotrimethylsilane. The mechanism of this reaction proceeds via oxidative addition of the N—O bond to afford 99, which undergoes alkene insertion into the Pd—N bond to provide alkyl-palladium complex 100. The exo-methylene product 101 is generated by [i-hydride elimination from 100, and isomerization to the desired pyrrole 98 occurs when chlorotrimethylsilane is added. 

The Wacker-type addition is the anti-addition of (most commonly) a heteroatom and a Pd(II) species across a C-C double bond. The Wacker-type oxidations are Pd(II)-catalyzed transformations involving heteroatom nucleophiles and alkenes or alkynes as electrophiles.27 In most of these reactions, the Pd(II) catalyst is converted to an inactive Pd(0) species in the final step of the process, and use of stoichiometric oxidants is required to effect catalytic turnover. For example, the synthesis of furan 33 from a-allyl-p-diketone 32 is achieved via treatment of the substrates with a catalytic amount of Pd(OAc)2 in the presence of a stoichiometric amount of CuCh-28 This transformation proceeds via Pd(II) activation of the alkene to afford 34, which undergoes nucleophilic attack of the enol oxygen onto the alkene double bond to provide alkylpalladium complex 35. p-Hydride elimination of 35 gives 36, which undergoes... 

Another tandem possibility is to use oxidative addition to generate the palladium(II) species that initiates cyclization (Scheme 6.44). The result is formation of both a C-C bond and a bond between an alkene carbon and a heteroatom. The C-C bond is formed by reductive elimination that generates a palladium(O) species. This is then returned to the palladium(II) state by oxidative addition, hence no added oxidant is required. The reaction has often been used in an intramolecular fashion to ensure regioselectivity. If the nucleophilic attack is slow, a by-product may occur, which is the Heck product arising from alkene insertion. Alkynes may also be used as substrates. 

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