Development of Catalytic Enantioselective Reactions Based on the Activation Technology by Chiral Ligands

我们已经开发了三种类型的新的活化技术;通过具有醚部分的手性氨基锂（1）来活化锂酯烯醇化物，通过手性氨基膦和过渡金属的络合物（2）来活化反应性较低的有机金属试剂，例如有机锌和有机硼烷，以及通过手性氨基醚（3）来活化锂硫醇。在含醚基的手性氨基锂存在下，烯醇化锂酯与亚胺的加成反应得到β-内酰胺，产率高达96%，ee值为74%，该技术也适用于烯醇化锂酯与α，β-不饱和酯的加成反应，产率高达67%，ee值为92%.在催化量的手性氨基膦和三氟甲磺酸铜（Ⅱ）存在下，4，4-二甲基-2-环己烯酮与二乙基锌反应，得到64%ee的乙基加合物.将此氨基膦-铜-二乙基锌体系应用于与亚胺的反应，得到97%ee的乙基加合物 关于我们 此外，该手性氨基膦配体适用于铑-芳基硼酸体系。在催化量的手性氨基膦和铑（I）存在下，芳基硼酸与2-烯酮反应生成3-芳基烷酮，产率高达99%，ee值为96%.在手性氨基醚存在下，硫醇锂与α，β-不饱和酯加成，生成的烯醇化酯锂对映选择性质子化。因此，用不含β-取代基的α，β-不饱和酯，可得到ee值高达92%的加成物。以带甲酰基的手性α，β-不饱和酯为受体，烯醇化锂与甲酰基以分子内方式反应，得到具有良好非对映选择性的环化产物。该环化反应很好地应用于（-）-neplanocin A的合成。少

We have developed three types of new activation technology ; the activation of lithium ester enolates by a chiral lithium amide having ether moiety (1), of less reactive organometallic reagents, such as organozinc and organoboran by a complex of a chiral amidophosphine and a transition metal (2), and of lithium thiolate by a chiral amino ether (3).1. In the presence of a chiral lithium amide having ether moiety, thereaction of lithium ester enolates with imines gave β-lactains in up to 96% yield and 74% ee. This technology was also applicable to the addition of lithium ester enolates to α,β-unsaturated esters to give the adducts in up to 67% yield and 92% ee.2. In the presence of a catalytic amount of a chiral amidophosphine and copper(II) triflate ; the reaction of 4,4-dimethyl-2-cyclohexenone and diethylzinc gave the ethyl adduct with 64% ee. The application of this amidophosphine-copper-diethylzinc system to the reaction with imine was successful, giving ethyl adducts in up to 97% y … More ield and 94% ee. Furthermore, the chiral amidophosphine ligand was applicable to the rhodium-arylboronic acid system. In the presence of a catalytic amount of the chiral amidophosphine and rhodium(I), aryl boronic acidsreacted with 2-alkenones to provide 3-arylalkanones in up to 99% yield and 96% ee. We are accumulating the experimental evidence that the chiral amidophosphine ligand is a so-called hemilabile ligand in this rhodium complex.3. In the presence of a chiral amino ether, lithium thiolates added to α,β-unsaturated esters and the resulting lithium ester enolate was enantioselectively protonated. Thus, using α,β-unsaturated esters having no β-substitoent, the addncts with up to 92% ee were obtained. When a chiral α,β-unsaturated ester having formyl group was used as an acceptor, the intermediate lithium enolate reacted withthe formyl group in the intramolecular fashion to give cyclized products in good diastereoselectivity. This cyclization was nicely applied to the synthesis of (-)-neplanocin A. Less