Boron enolates salts

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

Further insight into the P-borylation reaction of a,P-enones (Scheme 2.32) showed that the reaction can be carried out in THF, and the catalyst generated in situ from CuCl (5 mol%), the imidazolium salt (5 mol%), and NaO Bu (10 mol%), to form the [Cu(O Bu) (NHC)] as the catalysis initiating species. In this case, stable boron enolate products are formed which need to be hydrolysed by methanol to the ketone products [114]. 

The final product 63 retains the Ph3P+ group from the first vinyl phosphonium salt 59 and in the example below, using a boron enolate, this was hydrolysed to the stable phosphine oxide11 66. Note the creation of a quaternary carbon atom at a spiro centre. 

In order to improve the stereoselectivity of the aldol process even further, metal salts of enolate anions other than those bearing lithium have been examined. For example, both magnesium and boron enolates have been prepared. Magnesium enolates are very much like lithium enolates in their stereoselectivity, while boron enolates, where there are relatively short metal-oxygen bonds, give improved selectivity. For the boron enolates, the (Z)-enolate is generally more stable than its E)-isomer, and erythro- or 5yn-products are developed. 

Various enolate anions were trifluoromethylated regioselectively in good yields by a combination of 5-salt 17 with boron 59 (Eqs. 33-35). 

Chlorodifluoromethylketones underwent aldol reactions (Eq. 124) via zinc enolates, to afford good yields of a,a-difluoro-/ -hydroxy ketones, in a study by the Kyoto group [327]. Copper(I) or silver salt catalysis was essential and boron-trifluoride additive appeared to exert a key role in the conversion to the enolate. Earlier [328], chlorodifluoromethyl ketones had been converted to the di-fluoroenoxy silanes by the action of zinc in the presence of chlorotrimethyl silane. A difluoroenoxy silane was used by McCarthy and co-workers [329] to synthesise a kynureninase inhibitor (Eq. 125) Lewis acid-mediated reaction with a chloroglycinate installed the key carbon-carbon bond. 

The plant bufadienolide scillarenin (500) has been synthesized. The starting material was 15a-hydroxycortexone (501), which was converted into the diketone ketal (502) by cupric acetate oxidation at C(21), followed by selective ketalization and tosylate elimination. Protection at C(3) as the dienol ether, oxiran formation at C(20) with dimethylsulphonium methylide, and regeneration of the C(3)- and C(21)-oxo-groups by acid hydrolysis then provided (503). Selective reaction at C(21) with the sodium salt of diethyl methoxycarbonyl-methylphosphonate, and boron trifluoride rearrangement of the epoxide ring to the aldehydo-unsaturated ester (504), was followed by enol lactonization to the bufadienolide (505). This was converted, in turn, to scillarenin (500) via the 14,15-bromohydrin, by standard reactions. Unsubstituted bufadienolides have also been prepared by the same method. 

The reaction of the lithium enolate of 2-methyl-1-indanone with the thiophenium salt (35) leading to the 2-trifluoromethyl derivative in 51% yield is an exception. With all other in situ generated enolates of ketones, no trifluoromethylation was observed. To moderate the reactivity of the enolates, a boron Lewis acid (40) was added to form the boron complexes. This made a regio-, diastereo- and enantio-selective trifluoromethylation possible in good to high yields. ... 

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