Enantioselective and Z/E-Selective Conjugate Addition of α-Substituted Cyanoacetates to Acetylenic Esters Catalyzed by Bifunctional Ruthenium and Iridium Complexes
Enantioselective and Z/E-Selective Conjugate Addition of α-Substituted Cyanoacetates to Acetylenic Esters Catalyzed by Bifunctional Ruthenium and Iridium Complexes
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DOI：
10.1002/anie.201003585
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发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Ikariya, Takao
中科院分区：
文献类型：
--
作者：
Hasegawa, Yasuharu;Gridnev, Ilya D.;Ikariya, Takao
Catalytic and stereoselective formation of quaternary carbon centers remains a significant challenge in organic synthetic chemistry.[1] Metal-based catalytic methods including asymmetric alkylation and arylation of carbonyl compounds as well as enantioselective Diels–Alder reactions have been successfully applied for the creation of compounds with chiral quaternary carbon centers.[2] Asymmetric conjugate addition of pronucleophiles to α, β-unsaturated carbonyl groups presents one of the most powerful and atom-economic synthetic approaches to access enantiomerically enriched quaternary carbon skeletons for the synthesis of biologically active compounds. However, the chiral metal-based catalyst systems for enantioselective conjugate addition remain relatively rare, being limited to multimetal chiral catalysts [1f, g, 3] and chiral metal–enolates.[4] Our research group has developed a highly efficient asymmetric conjugate addition of 1, 3-dicarbonyl groups to cyclic enones and nitroalkenes with our bifunctional chiral amido Ru catalysts 1 [5][Ru (Tsdpen)(η6-arene)](Tsdpen: N-(p-toluenesulfonyl)-1, 2-diphenylethylenediamine).[6] The use of α-cyanoacetate as a pronucleophile combined with diazoesters in the presence of bifunctional chiral Ir amido catalysts 2 [7][Cp* Ir (Tsdpen)](Cp*= η5-C5-(CH3) 5) also resulted in the direct amination of activated cyanoacetate to provide products with enantiomerically enriched tertiary carbon centers.[8] Preliminary mechanistic studies showed that the key stage of the catalytic cycle is the deprotonation of the acidic pronucleophile with the chiral amido catalyst which leads to the stereoselective formation of an N-bound amine complex.[6c] The resulting amine complex bearing a metal-bound nucleophile readily reacts with suitable electrophiles to give CÀN bond-formation products in a highly stereoselective manner.[8] We reasoned that other electrophiles may also react with this catalyst–substrate complex in a similar way to afford new enantioselective catalytic transformations. Herein, we report an enantioselective and Z/E-selective catalytic CÀC bond-forming reaction between α-substituted cyanoacetates and acetylenic esters using bifunctional Ru (1) and Ir (2) catalysts to yield chiral adducts having a quaternary carbon center. Moreover, NMR and computational studies revealing the origin of enantioselectivity in this reaction are also reported. We have found that the conjugate addition of cyanoacetate 3 to acetylenic diester 4a in the presence of bifunctional Ru (1) or Ir (2) catalysts (cyanoacetate/acetylenic ester/cat.= 100: 100: 1) at 08C gave the corresponding chiral adducts 5 with good to excellent enantiomeric excess and Z/E selectivity in almost quantitative yields (Scheme1). Table1 lists representative results for the reaction (see the Supporting Information for more details). Chiral Ru and Ir complexes work equally well for this reaction, in contrast to the reaction of cyanoacetate 3a and diazoesters,[8] in which the chiral Ir catalyst was far superior to the Ru catalyst.As seen in Table 1, the stereochemical outcome of the reaction is significantly influenced by the structures of the catalysts as well as the reaction conditions. The optimal catalysts are 1b and 2b with the Tsdpen ligand (entries 1 and 2; aryl= hexamethylbenzene for the Ru catalyst and aryl= Cp* for the Ir catalyst). Other Ru complexes with mesitylene (1d) and p-cymene (1e) aryl groups gave unsatisfactory
