Copper-Catalyzed Addition of Grignard Reagents to in situ Generated Indole-Derived Vinylogous Imines

Chiral indole derivatives are ubiquitous motifs in pharmaceuticals and alkaloids. Herein, the first protocol for catalytic asymmetric conjugate addition of Grignard reagents to various sulfonyl indoles, offering a straightforward approach for the synthesis of chiral 3-sec-alkyl-substituted indoles in high yields and enantiomeric ratios is presented. This methodology makes use of a chiral catalyst based on copper phosphoramidite complexes and in situ formation of vinylogous imine intermediates.     

Catalytic Enantioselective Addition of Alkylzirconium Reagents to Aliphatic Aldehydes

A catalytic methodology for the enantioselective addition of alkylzirconium reagents to aliphatic aldehydes is reported here. The versatile and readily accessible chiral Ph-BINMOL ligand, in the presence of Ti(OⁱPr)₄ and a zinc salt, facilitates the reaction, which proceeds under mild conditions and is compatible with functionalized nucleophiles. The alkylzirconium reagents are conveniently generated in situ by hydrozirconation of alkenes with the Schwartz reagent. This work is a continuation of our previous work on aromatic aldehydes.     

Highly Enantioselective Catalytic Addition of Grignard Reagents to N‐Heterocyclic Acceptors

General methods to prepare chiral N‐heterocyclic molecular scaffolds are greatly sought after because of their significance in medicinal chemistry. Described here is the first general catalytic methodology to access a wide variety of chiral 2‐ and 4‐substituted tetrahydro‐quinolones, dihydro‐4‐pyridones, and piperidones with excellent yields and enantioselectivities, utilizing a single catalyst system.     

铜催化二乙基锌对亚胺的不对称加成反应研究进展

潜手性物质亚胺的不对称催化加成反应是近年来不对称催化反应中的热点研究领域之一,本文对近十年来铜催化二乙基锌对亚胺类化合物的不对称加成反应研究进展进行了综述。     

二乙基锌对原位产生吲哚亚胺的对映选择性加成反应

发展了乙基锌对原位产生的不饱和亚胺的对映选择性共轭加成,磺酰吲哚衍生物在乙基锌存在下原位生成不饱和亚胺,手性亚磷酰胺配体-铜络合物催化二乙基锌对该原位产生的不饱和亚胺反应以最高99%的产率和80%的对映选择性得到了一系列3位取代的光学活性的吲哚衍生物.     

Regioselective Addition of Grignard Reagents to Substituted Tropones

Methyl magnesium bromide has been reacted with a variety of substituted tropones to establish addition regioselectivity patterns. High levels of selectivity were observed in each case examined, and the resultant dihydrotropones were easily converted into highly substituted cycloheptatrienes.     

Copper‐Catalyzed Regio‐ and Enantioselective Addition of Silicon Grignard Reagents to Alkenes Activated by Azaaryl Groups

A new application of silicon Grignard reagents in C(sp³)?Si bond formation is reported. With the aid of BF₃?OEt₂, these silicon nucleophiles add across alkenes activated by various azaaryl groups under copper catalysis. An enantioselective version employing benzoxazole‐activated alkenes as substrates and a CuI‐josiphos complex as catalyst has been developed, forming the C(sp3)?Si bond with good to high enantiomeric ratios (up to 97:3). The method expands the toolbox for “conjugate addition” type C(sp³)?Si bond formation.     

Conjugate Addition of Grignard Reagents to Substituted Isopropylidene Methylenemalonates

The conjugate addition of various nucleophilic reagents to unsaturated Knoevenagel-type products derived from Meldrum's acid (the cyclic isopropylidene ester of malonic acid) has been the subject of several investigations¹. In most cases the addition occurs rapidly and the adducts are obtained in high yield. The ease with which these conjugate additions take place can be attributed to the special stability of the carbanionic intermediates. The intermediates formed in these reactions are formally anions of monosubstituted isopropylidene malonates and their low basicity can be attributed to the six-membered ring which holds the two carbonyl groups co-planar causing a high degree of conjugative stabilization¹.     

Enantioselective Addition of Chiral Organotitanium Derivatives to Aldehydes

Alkoxy- and aryloxy-organotitanium compounds 2–4 derived from (S)-2-methyl-1-butanol, (R)-2-butanol, (-)-menthol, quinine, cinchonine, and (S)-1.1′-binaphthol are added to aromatic aldehydes to give optically active alcohols 5–10 in enantioselectivities of up to 88% e. e., with nucleophilic transfer of methyl, phenyl, and 1-naphthyl groups. The Tables 1–3 list the effects of varying the reagents, the substrates, and the reaction conditions of the new asymmetric synthesis.     

Development of Highly Active Chiral Titanium Catalysts for the Enantioselective Addition of Various Organometallic Reagents to Aldehydes

The catalytic enantioselective carbonyl addition reaction has long attracted the interest of chemists because of its synthetic importance. Although many highly enantioselective reactions have been developed, with few exceptions the reactions are carried out at relatively high catalyst loadings, making them less practical for scale‐up applications. In addition, organometallic reagents employed as carbon nucleophiles have been limited to those with relatively low reactivity, such as diorganozincs and arylboronic acids. In an effort to enhance the practicality, a highly active and enantioselective chiral titanium catalyst system was recently developed in our laboratory, enabling the enantioselective carbonyl addition reaction to aldehydes using various organometallic reagents (RM; M = MgX, Li, BY₂, ZnX, AlMe₂) at lower catalyst loadings (≤5 mol %).

     

Using Natural Cinchona Alkaloids to Promote the Enantioselective Addition of Dialkylzinc to N－Diphenylphosphinylimines

Cinchona alkaloids are utilized as chiral ligands to promote the enantioselective addition of dialkylzinc to N-diphenyiphosphinylirnlnes affording enantiomerically enriched N-diphenyiphosphinylamines in up to 91% ee.     

不对称合成中手性杂环配体的结构与催化活性

总结了烷基锌对醛的不对称加成中手性杂环配体的结构与催化活性的关系,并讨论了若干影响配体催化活性的因素。