Active methylene compounds organometallics

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. 

The reaction of A-acyliminium ions with nucleophilic carbon atoms (also called cationic x-amidoalkylation) is a highly useful method for the synthesis of both nitrogen heterocycles and open-chain nitrogen compounds. A variety of carbon nucleophiles can be used, such as aromatic compounds, alkcncs, alkyncs, carbcnoids, and carbanions derived from active methylene compounds and organometallics. 

In general, examples of substitution of sodium and potassium in organometallic derivatives by fluorine are limited to the salts of active methylene compounds. Their fluorination is achieved with perchloryl fluoride.fluorine, N-F reagents. " and xenon difluoride " (Table 10). The fluorination of metal enolates is discussed under metal-assisted substitution ot... 

The Michael-type addition reaction of a carbonucleophile with an activated olefin constitutes one of the most versatile methodologies for carbon-carbon bond formation [1]. Because of the usefulness of the reaction as well as the product, many approaches to the asymmetric Michael-type addition reactions have been reported, especially using chirally modified olefins [2-8]. However, the approach directed towards the enantioselective Michael-type addition reaction is a developing area. In this Chapter, the recent progress of the enantioselective Michael-type addition reaction of active methylene compounds and also organometallic reagents with achiral activated olefins under the control of an external chiral ligand or chiral catalysts will be summarized [9]. 

In most cases, treatment of allylic halides containing one ASG with a nucleophile does not result in formation of electrophilic cyclopropanes (MIRC product) instead, other reaction pathways are followed, e.g. addition, substitution, rearrangement and elimination reactions.However, with certain alkenes or nucleophiles or under the appropriate conditions a conjugate addition-nucleophilic substitution pathway is favored, resulting in cyclopropanes substituted with one ASG. Representative examples are compiled in Tables 20 and 21 where organometallic compounds or active methylene compounds are used as the nucleophilic species in combination with allyl bromides containing an ester or a sulfone as ASG. 

Organosodium compounds are prepared from sodium and other organometallic compounds or active methylene compounds by reaction with organic halides, cleavage of ethers, or addition to unsaturated compounds. Some aromatic vinyl compounds and allyhc compounds also give sodium derivatives. 

Stereochemistry of Pd-catalyzed allylation of nucleophiles has been studied extensively. In the first step, formation of 7r-allylpalladium complexes 37 by the attack of Pd(0) on allylic compounds 36 proceeds with inversion of configuration (anti attack). Subsequent reaction of 37 with nucleophiles occurs in different stereochemistry depending on the nature of the nucleophiles. The soft (stabilized) nucleophiles which are derived from conjugate acids with < 25, such as active methylene compounds, attack 37 from the backside of the Pd atom to give 38 with inversion of stereochemistry. Thus overall retention is observed. On the other hand, hard nucleophiles (pK > 25), typically organometallic compounds of main group metals (Mg, Zn, B, Sn and others) generate 39 by transmetallation, and subsequent reductive elimination affords 40. Both the transmetallation and... 

Finally, a homogeneous heterobimetallic Pd(COD)Cl-SnCl3 catalyst for the 5 reactions that form a new C-C bond between primary and secondary allylic alcohols and nucleophiles such as arenes, heteroarenes, active methylene-, and organometallic compounds has been reported. Yields range from 60 to 92%. The Sf 2/Sj 2 ratio is usually high, even up to 100/0, although exceptions occur. The reaction is successful when ben-zylic and propargylic alcohols or symmetric and unsymmetric allyl ethers are used in place of allylic alcohols. 

The a-amidoalkylation reaction, which involves the addition of carbon nucleophiles (primarily aromatic rings, alkenes, cyanides, isocyanides, alkynes, organometallic and active methylene-containing compounds) to substituted amides (89) where X is a leaving group (Scheme 17), has been extensively re-viewed. A variety of organometallic condensations have since been reported which extend the scope of this reaction. The reactive intermediates in these reactions are considered to be N-acylimines (88) or N-acyliminium salts (SKI). Direct displacement of the a-haloalkylamide precursors (89 X = halogen) cannot in certain cases be discounted. 

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