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

我们开发了三种新的活化技术；具有醚部分(1)的手性锂酰胺对锂酯烯醇化的活化；反应性较低的有机金属试剂，如通过手性氨基膦和过渡金属(2)的配合物对有机锌和有机硼的活化；以及通过手性氨基醚(3)对硫代锂的活化。在具有醚段的手性锂酰胺存在下，锂酯与亚胺发生烯醇化反应，得到收率高达96%、ee达74%的β-乳酰胺。该工艺同样适用于α，β-不饱和酯与锂酯烯醇酯的加成反应，加成产物收率高达67%，ee达92%。在手性氨基膦和三酸铜（II）的催化量存在下；4,4-二甲基-2-环己酮与二乙基锌反应得到ee含量为64%的乙基加合物。该氨基膦-铜-二乙基锌体系在与亚胺的反应中得到了成功的应用，得到的乙基加合物的收率高达97%。此外，手性氨基膦配体适用于铑-芳基硼酸体系。在手性氨基膦和铑(I)的催化量存在下，芳基硼酸与2-烯酮反应生成3-芳基烷酮，收率高达99%，ee达96%。我们正在积累实验证据，证明手性氨基膦配体是这种铑络合物中所谓的半可溶配体。在手性氨基醚存在下，硫代酸锂加入到α、β-不饱和酯中，得到的锂酯烯酸酯被对映选择性质子化。因此，采用不含β取代基的α，β-不饱和酯，可以得到ee含量高达92%的加成物。以含甲酰基的手性α，β-不饱和酯为受体时，中间体烯酸锂与甲酰基发生分子内反应，生成具有良好非对映选择性的环化产物。这种环化很好地应用于(-)-neplanocin A. Less的合成

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