Followers Gives The Boast On GANT61SC144

62 One example is shown in eq GANT61 39. The hydroboration of 120 followed by directed hydrogenation utilizing Crabtrees catalyst, Ir ] PF6 ), gives a reduced product with extremely high stereoselectivity. 7. Asymmetric Hydrovinylation of Norbornene We've already alluded towards the initial outcomes on hydrovinylation of norbornene as one of many 1st metal catalyzed asymmetric C C bond forming reactions as well as the remarkable dependence of the reaction on the cone angle of the phosphine employed . 11b,19 The results obtained with the new ligands are shown in eq 40 and Table 13. 28 Ozonolysis of 18 followed GANT61 by oxidation of the resulting aldehyde gave norbonane 2 carboxylic acid, the enantiomers of which were converted into esters of methyl mandelate by the normal procedure utilizing DCC.
The absolute configuration of these diastereomers had been totally established before. 64 As expected, phosphines with big cone angles give exclusively the 1:1 adduct in almost quantitative yield and modest enantioselectivity . Note the use of highly dissociated counteranions in these SC144 reaction. No trace of the 2:1 adduct 19 is observed under these conditions. The selectivity with the phosphoramidite ligands depends upon both the counteranion as well as the nature of the secondary amine appendage. Whereas the isomer is really a very good ligand , the corresponding diastereomer 80 gives less than 2% of the product . Suprisingly, for the ligand 80 , the counter anion determines whether or not 1:1 or 1:2 adduct is made. With NaBARF only 1:1 adduct is made , whereas AgSbF6 , now gives exclusively the 2:1 adduct 19 in almost quantitative yield ! Phospholane 15 gives mostly the 2:1 adduct .
A modest enantioselectivity of 33% has been observed for this product as determined by the Mosher ester approach. 28 As we have documented before, Protein precursor the use of AgOTf as an additive is vital for the ligands like 15 with no hemilabile side chain. Chelating ligands inhibit the reaction under the common conditions reported here. 8. Applications of Asymmetric Hydrovinylation Reactions 8. 1 or 2 Arylpropionic Acids 2 Arylpropionic acids are the most extensively applied non steroidal antiinflammatory agents . 65 Naproxen, 2 2 propionic acid, which is the only NSAID at present sold in enantiomerically pure form is resolved by a classical resolution. 66 Most members of this critical class of compounds can in principle be synthesized by oxidative cleavage of the double bond of the hydrovinylation products of vinylarenes .
With SC144 our recent syntheses of various 3 arylbutenes of extremely high enantiomeric purity 47 this becomes a viable route. Hence Table 9 shows highly enantioselective syntheses of compounds 89, 90, 91 and 92, precursors of ibuprofen, naproxen, flurbiprofen and fenoprofen respectively, via hydrovinylation of the appropriate vinylarene utilizing the ligand 87. 66 We've because carried out the HV of 3 bromostyrene in extremely high ee as well as the product from this reaction has been converted into ketoprofen via 125. 67 Oxidative cleavage by ozone of the double bond in the HV products followed by further oxidation of the resulting aldehydes by KMnO4 or NaClO2 give ibuprofen and flurbiprofen in acceptable yield without having any racemization at the intermediate aldehyde stage .
More electron rich naproxen substrate 90 was very best oxidized with NaIO4 and KMnO4. These GANT61 conditions also gave the top yields for the oxidation of the ketoprofen precursor 3 1 butene. Likewise, the fenoprofen precursor 125 was obtained utilizing RuCl3/NaIO4 from the corresponding 3 arylbutene. In each case the ee of the final product was confirmed by chiral stationary phase gas chromatography of the menthyl esters. 28b,43a 8. 2 Curcumene and ar Turmerone 68 Several critical classes of all-natural products, among them, bisabolanes, heliannanes, serrulatanes and pseudopterosins are characterized by a benzylic chiral center, generally carrying a methyl group at this position.
69 Diverse biological activities exhibited by these compounds include antiinflammatory, antiviral and antimycobacterial properties and they have attracted SC144 considerable interest from synthetic chemists. No less than 12 non racemic syntheses of the simplest member of this class of compounds, curcumene are recognized. curcumene and associated ar turmerone are the constituents of a sizable number of GANT61 vital oils and it has been amply demonstrated that intermediates for their synthesis could in principle be applied to get a number of other bisabolane along with other associated terpenes. 69a In spite of their rather straightforward structures, the stereo center at the benzylic position poses a considerable challenge in the asymmetric synthesis of even curcumene. 70 SC144 Arguably, the shortest route starts with citronellal and involves 6 steps and multiple chromatographic separations to generate curcumene in 28% overall yield. 71 An exceptionally brief synthesis based on asymmetric hydrovinylation of 4 methylstyrene is shown in Scheme 10. This synthesis starts with hydrovinylation of 4 methylstyrene. In the racemic series, the hydrovi