Catalytic asymmetric cross-coupling reactions with secondary alkyl halides

3 Catalytic Asymmetric Cross-Coupling Reactions with Secondary Alkyl Halides 

and DMF, is critically important for the reactions. The exact mechanism of these transformations still remains to be elucidated. 

The Pd- or Ni-catalyzed alkyl couphng involving alkylmetals and/or alkyl electrophiles has been widely apphed to the synthesis of natural products both in terms of producing their intermediates and the final targets. Only some representative examples of those that involve the use of a Negishi coupling are listed in Table 3.16. 

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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]. 

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