Electrophilic reactions background

Catalytic symmetric synthesis of P-stereogenic phosphines by cross-coupling of secondary phosphines with benzyl or other alkyl halides was promoted by chiral ft and Ru complexes [112-114]. The key step is believed to be the nucleophilic attack of a metal-phosphido complex on a free electrophile the background reaction of the unactivated nucleophilic substrate is much slower. The origin of enantioselec-tivity, as in the Pd-catalyzed asymmetric cross-couplings described above, is the interconversion of diastereomeric phosphido complexes, whose speciation and relative rates of nucleophilic attack determine the product ratio. In the case of ft ((R./ )-Me-DuPhos)(Ph)(PMels), as with the Pd analog in Scheme 43 above, the major product phosphine was formed from the major diastereomeric phosphido complex (Scheme 63) [112-113]. 

With this as background let us now examine each of the electrophilic aromatic substitution reactions presented m Table 12 1 m more detail especially with respect to the electrophile that attacks benzene... 

In 1999, the group of Lygo reported that the use of N-anthracenylmethyl-dihydrocinchonidinium chloride (6e) significantly improved the enantioselectivity of the alkylations with substituted benzyl bromides, enhancing the utility of this approach to a,a-dialkyl-a-amino acids [30]. For reproducible results, the mixed solid base KOH/K2CO3 must be freshly prepared before use. The lack of stereoselectivity in the reactions with other electrophiles was ascribed to competing, non-selective background alkylation (Scheme 2.10). 

Protonation does not only catalyze the isomerization, but also contributes to the nonselective background reaction by enhancing the electrophilicity of the imines (via 53). Therefore, the H+ concentration must be kept relatively low and acetic add (up to 1 equiv) was identified as an acceptable compromise. Stronger acids promote the nonenantioselective background reaction, whereas addition of bases resulted in a dramatic deceleration [12h]. 

To be accurate, the definition should be restricted to asymmetric reactions catalyzed by a combination of l,r-binaphthalene-2,2 -diol (BINOL, 4) and Ti(0 -Pr)4. Nonetheless, this chapter will give some background on non-chiral Lewis acid promoters, and include other asymmetric catalytic systems. We will not discuss the allylations that are promoted by Lewis bases, which are reviewed elsewhere, nor cover the reactions with other electrophiles. Excellent reviews already exist on "Selective Reactions Using Allylic MetaM and Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , as well as in the comprehensive monograph "Modern Carbonyl Chemistry. The use of BINOL-based catalysts in other fields of organic synthesis has also been reviewed. ... 

This chapter focused upon reactions at unsaturated centers alkenes, alkynes, arenes, and carbonyls. A large variety of additions and eliminations was examined. The complexity in the examples showed how diverse the possibilities are for additions and eliminations to such centers. One can have electrophilic, nucleophilic, and radical pathways for almost all reaction classes, and the dominant product depends upon the structures of the reactants and the experimental conditions. You should now be able to write the electron pushing for the standard reaction mechanisms (El, E2, SeAr, etc.), as well as be able to predict and examine experimentally the variations that are possible. Given this background on unsaturated centers, we turn our attention to reactions that occur at saturated centers, which is the first major topic of the next chapter. 

The iodoaminocyclization of hydrazones proceeded under very mild conditions to generate pyrazolines with high selectivity (Scheme 7.33 and Example 7.13) [56]. The organocataly tic reaction was promoted by the use of a bifunctional thiourea catalyst Using A -iodopyrrolidinone as the source of electrophilic iodine leads to the highest selectivity for the reaction. Control reactions were carried out and the authors noted that strict control of the temperature was needed to prevent a background reaction. Additionally, including molecular sieves in the reaction mixture led to an increase in the selectivity. 

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