Chiral bidentate tertiary

Stelzer and co-workers reported a number of chiral water-soluble secondary phosphines [14], prepared by nucleophilic phosphination of primary phosphines with fluorinated aryl sulfonates in the superbasic medium DMSO/KOH. Further reaction with alkyl halides gives bidentate tertiary phosphines with P-chirality, but only racemic versions have been reported so far. Hanson et al. introduced so-called surface-active phosphines into asymmetric aqueous-phase catalysis. One of the main problems inherent to two-phase catalysis is the often very low miscibility of the substrates in the aqueous phase. Insertion of long alkyl chains between phosphorus atoms and phenyl groups in sulfonated phosphine ligands has been proven to increase reaction rates in the Rh-catalyzed hydroformylation of 1-octene [15], This concept was extended to a number of chiral ligands, i.e., the monoden-... 

Access to optically pure phosphine oxides is important for the preparation of chiral bidentate ligands that have found application in asymmetric hydrogenation. Tertiary phosphine oxides are available in high enantiomeric excess using menthyl 2-phosphinylacetate 1... 

Catalytic enantioselective allylic substitutions of aiyl- and alkyl- substituted phosphates (63) with commercially available allenylboronic acid pinacol ester (64) resulted in the formation of tertiary or quaternary C-C bonds. Reactions were promoted by sulfonate-bearing chiral bidentate Af-heterocyclic carbene (NHC) complexes of copper (66), which exhibited the unique ability to furnish chiral products arising from the Sj.,2 mode of addition. Allenyl-containing products (65) were generated in up to 95% yield, >98% 8 2 selectivity and 99 1 enantiomeric ratio (Scheme 21). ... 

Nucleophilic addition to less reactive ketone carbonyls by Lewis acid activation is also possible. Evans and co-workers have reported enol silane addition to pyruvate esters mediated by chiral copper Lewis acids (Sch. 36) [72]. The aldol reactions proceed with high facial selectivity to provide the tertiary alcohol products 153. The chemical efficiency is, however, reduced when a bulky alkyl group is present at the ketone carbonyl. Addition of more functionalized enol silanes (155) to keto esters enables the establishment of two contiguous chiral centers, a substitution pattern present in a variety of natural products. The stereochemistry of the major product is syn, irrespective of the enol silane geometry. Once again, bidentate coordination of the substrate to the Lewis acid was essential for obtaining high selectivity. 

This study constitutes a further example of how efficient catalytic reactions can be developed despite the presence of complex solution equilibria. Originally, this chemistry was developed in a non-donor solvent rather than using an excess of donor as solvent. By so doing, the critical effects of additives, both chiral and achiral, are more readily appreciated. Indeed, incorporation of lithium bromide and an achiral, bidentate ligand in addition to 5 are essential for selectivity. The effects of these additives are particularly interesting. Tertiary diamines, e.g. 6 and its analogues,... 

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