Chiral lithium phosphate

Antilla developed a catalytic enantioselective desymmetrisation of meso-epoxides with thiols by using chiral lithium phosphate 17. A wide range of epoxides and aromatic thiols were observed with high enantioselectivities (Scheme 2.12). ... 

Phosphate-derived a-oxycarbanions can rearrange into a-hydroxy phosphonates. This class of rearrangement is known to proceed with retention of configuration at the carban-ion terminus. The enantioselective version of this rearrangement has been developed using a chiral lithium amide as a base (equation 115) . The reaction of benzyl dimethyl phosphate 182 with amide R,R)-63 in THF gave the hydroxy phosphonate (5 )-183 in 30% in enantioenriched form (52% ee). 

Employing the chiral lithium amide (R,R)-3 as a base in THF at —78°C gave the hydroxy phosphonate 84 in 30% yield and 52% ee upon deprotonation of phosphate 83 (Scheme 60)102,103. The use of BuLi as base with (—)-sparteine as chiral ligand in ether at —78 °C resulted in a lower optical activity (8% ee) and 65% yield102. 

Based on acid-base combination chemistry, Ishihara developed a catalytic enantioselective cyanosilylation of ketones by using chiral (J )-Ph2-BINOL-derived lithium phosphate, which was prepared in situ from phosphoric acid... 

Scheme 2.11 Enantioselective cyanosilylation of ketones with the use of chiral lithium(i) phosphate.

A 100-mL round-bottom flask containing a magnetic stirrer is capped with a rubber septum and charged with 15 mmol of borinate. 15 mL of diethyl ether arc added and the reaction is cooled to 0°C. 2.04 mL (22.5 mmol) of dichloromethyl methyl ether are added followed by 16.2 mL (30 mmol) of lithium lert-bu-toxide. The ice bath is removed and the mixture stirred at r.t. for 1 h. A slightly exothermic reaction develops and a white precipitate forms. The reaction mixture is cooled to 03C and 18 mL (45 mmol) of pH 8 phosphate buffer arc added, followed by 5.1 mL (45 mmol) of 30% hydrogen peroxide. The ice bath is removed and the mixture stirred for 12 h. The phases are separated, the aqueous phase extracted with two 15-mL portions of diethyl ether, the combined extracts washed with two 15-mL portions of water, then aq NaCl, dried over MgS04 and filtered. The volatiles are removed under reduced pressure and the residual oil is purified by bulb-to-bulb distillation. The chemical purity of the ketones is determined by GC using a 5% SP 2100 on Chromosorb W column and is usually >95%. The chiral ketones are further purified by preparative GC. For further examples, see Table 2. 

In contrast to the number of studies on asynunetric HWE reactions using chiral phosphonates, only a few enantioselective HWE reactions using a combination of achiral phosphonates and chiral Ugands are known [69,70]. Koga and coworkers reported the first enantioselective HWE reaction of diethylphospho-noacetonitrile and 4-terf-butylcyclohexanone using a stoichiometric amount of lithium 2-aminoalkoxides as a chiral base [Eq. (23)] [71]. The a,P-unsaturated nitrile was obtained in 92% yield with 52% ee. When the racemic aldolate intermediate was treated with a chiral diamine, a similar result was obtained. These results show that dissociation of the Uthium aldolate to the a-hthiated phospho-noacetonitrile and recombination to the aldolate reversibly occurs during the reaction, and the enantioselectivity is controlled by the rate of the eUmination reaction of the phosphate. 

In this chapter, we reviewed recent developments regarding lithium, sodium, and potassium salt based-catalysis, with a particular focus on asymmetric catalysts. While these alkali-metal salts have traditionally been used as simple bases, recent advances based on chiral multifunctional acid-base combination chemistry, using chiral crown-alkali-metal complexes, chiral lanthanoid/alkali-metal complexes, chiral alkali-metal alkoxides, and chiral alkali-metal phosphates, have also been outstanding. These synergic acid-base catalyst systems should enable more efficient and/or new transformations that have not been possible thus far using conventional catalysts that only rely on Lewis acidity or Bronsted/Lewis basicity. 

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