Barnes, David M. published the artcileDevelopment of a catalytic, asymmetric Michael addition in the synthesis of endothelin antagonist ABT-546, Recommanded Product: (3aS,3a’S,8aR,8a’R)-2,2′-(Cyclobutane-1,1-diyl)bis(3a,8a-dihydro-8H-indeno[1,2-d]oxazole), the publication is ACS Symposium Series (2002), 45-59, database is CAplus.
The selective endothelin A antagonist ABT-546 I is prepared enantioselectively on large (13 mol) scale using the catalytic addition of ketoester II to nitrostyrene III in the presence of bisoxazoline IV and magnesium triflate as the key step. E.g., magnesium triflate is hydrated in chloroform; ligand IV is added and the mixture stirred for about 1 h to generate the active catalyst. E.g., II and III are added with mol. sieves to give a 0.2 M solution; N-methylmorpholine is added as an amine cocatalyst when the mixture is dry and the reaction is stirred to give intermediate V in 83% yield and 88% ee on 13 mol scale. The Michael addition reaction was extensively optimized. No other bisoxazoline ligand tested was as effective as IV. Other magnesium salts with coordinating anions are less effective as catalysts. An amine cocatalyst is necessary for high stereoselectivity in the Michael addition Chloroform is the best solvent for the Michael addition, although toluene also is effective. The presence of water during the generation of the active catalyst is necessary for high yields, but the presence of water during the reaction inhibits the reaction and decreases selectivity; the use of mol. sieves is necessary to obtain product in high yields. The purity of the substrates in the enantioselective Michael addition is important for good rates and selectivities. The scope of the asym. Michael addition reaction of ketoesters to nitroolefins to give nitroketoesters is extended to other ketoester and malonate nucleophiles such as di-Et malonate, and to other nitroolefins such as β-nitrostyrene and 1-nitro-1-heptene.
ACS Symposium Series published new progress about 182122-10-7. 182122-10-7 belongs to isoxazole, auxiliary class BOX or PyBox,BOX or PyBox, name is (3aS,3a’S,8aR,8a’R)-2,2′-(Cyclobutane-1,1-diyl)bis(3a,8a-dihydro-8H-indeno[1,2-d]oxazole), and the molecular formula is C24H22N2O2, Recommanded Product: (3aS,3a’S,8aR,8a’R)-2,2′-(Cyclobutane-1,1-diyl)bis(3a,8a-dihydro-8H-indeno[1,2-d]oxazole).
Referemce:
https://en.wikipedia.org/wiki/Isoxazole,
Isoxazole | C3H3NO – PubChem