Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Hetero‐triarylmethanes from Racemic Indolyl Alcohols

The direct enantioselective 1,4‐ and 1,8‐arylations of 7‐methide‐7H‐indoles and 6‐methide‐6H‐indoles, respectively, generated in situ from diarylmethanols, with electron‐rich arenes as nucleophiles, has been achieved in the presence of chiral phosphoric acids (CPAs). These two remote activation protocols provide an efficient approach for the construction of diverse hetero‐triarylmethanes in high yields (up to 97 %) and with excellent enantioselectivities (up to 96 %). Mechanistically inspired experiments tentatively indicate that the catalytic enantioselective 1,4‐addition as well as the formal S_N1 substitution could proceed efficiently in the similar catalytic systems. Furthermore, the modification of the catalytic system and diarylmethanol structure successfully deviates the reactivity toward a remote, highly enantioselective 1,8‐arylation reaction. This flexible activation mode and novel reactivity of diarylmethanols expand the synthetic potential of chiral phosphoric acids.     

手性磷酸催化剂在不对称合成中的应用

手性磷酸是2004年报道的一类具有新型结构的强酸性Bronsted酸催化剂,近几年来的研究取得了很大的进展,已经成为有机小分子催化剂的一个重要分支。手性磷酸在催化一系列亚胺的加成和还原反应比如Mannich、亚胺的氢转移、亚胺的膦酰化、Pictet-Spengler、 Strecker、aza-Diels-Alder、 Friedel-Craft和α-重氮酯的烷基化等反应时都表现出了非常好的催化活性和立体选择性。本文主要综述了手性磷酸催化剂应用于亚胺相关反应的研究进展。     

BINOL衍生的手性磷酸催化的不对称反应研究进展

综述了近年来BINOL衍生的手性磷酸作为一类强酸性Brφnsted酸催化剂,在不对称氢转移反应、Friedel-Crafts, Mannich, Aza Diels-Alder, Aza-ene-type, Pictet-Spengler等反应中的研究进展.参考文献37篇.     

Enantioselective Robinson‐Type Annulation Reaction Catalyzed by Chiral Phosphoric Acids

Let′s resolve our differences : Implementation of an enantioselective Michael addition followed by an intramolecular aldol reaction catalyzed by two phosphoric acids has enabled the synthesis of cyclohexenone derivatives with excellent enantioselectivities. Prominent kinetic resolution was observed in the latter reaction. Ar=aromatic group, X=H, halogen, Y=H, Me, halogen.

     

手性磷酸催化的吲哚与乙醛酸乙酯亚胺的不对称傅克烷基化反应

在20%手性磷酸催化下,吲哚及其衍生物与乙醛酸乙酯亚胺发生不对称傅克烷基反应,合成了9个吲哚取代的甘氨酸衍生物(其中两个为新化合物),其结构经1H NMR表征。     

手性磷酸在不对称反应中的应用

手性磷酸催化剂因其在不对称催化反应中表现出的高效、高对映选择性而受到人们越来越多的关注.含1,1'-联二萘酚(BINOL)骨架的手性磷酸类催化剂已被广泛用于亚胺的不对称氢转移、Friedel-Crafts反应和Mannich反应等许多重要的有机合成反应.手性磷酸具有同时提供质子和接受质子的双功能作用,因此可以同时活化两个反应底物.含BINOL骨架的手性磷酸可以通过改变BINOL骨架3,3'-位上的取代基调控空间位阻和手性磷酸的酸性,因此可以调节反应的对映选择性.为了合理地设计新的手性磷酸催化剂,扩大其应用范围,最近人们对手性磷酸不对称催化反应机理进行了初步的理论计算研究并取得了显著进展.综述了手性磷酸在不对称反应中的部分研究工作,尤其是理论研究领域的最新成果.     

Phosphoric Acid Catalyzed Asymmetric [2+2] Cyclization/Penicillin–Penillonic Acid Rearrangement

Enantioselective synthesis of imidazolidin‐5‐ones through a phosphoric acid catalyzed reaction between azlactones and N‐substituted β‐carbolines is reported. The reaction takes place via an initial formal [2+2] cycloaddition to generate an α‐amino‐β‐lactam, which subsequently undergoes an acid‐catalyzed asymmetric penicillin–penillonic acid (PPA) rearrangement with high diastereo‐ and enantioselectivity. To the best of our knowledge, this represents the first [2+2] cyclization of azlactones with imines and the first asymmetric PPA rearrangement, which are linked together by the phosphoric acid catalyst.     

Gold(I)‐Catalyzed Asymmetric Desymmetrization of meso‐Alkynyl Diols and Kinetic Resolution of the Corresponding dl‐Diols: Effects of Celite Filtration and Silver Salts

The asymmetric desymmetrization of meso‐2‐alkynylbenzenediols through the use of a combination of axially chiral diphosphine(AuCl)₂ precatalysts and silver salt co‐catalysts gave optically active isochromene compounds with high enantioselectivities in good yields. The corresponding dl ‐diol isomers underwent efficient kinetic resolution to give the cyclized isochromenes and recovered diols with high enantioselectivities under similar conditions. The high reactivity and selectivity in the desymmetrization of the meso‐diols is independent of the combination of axially chiral diphosphine(AuCl)₂ precatalyst and silver salt co‐catalyst, whereas the corresponding tricarbonylchromium complexes of alkynylbenzenediols were affected by the combination of the diphosphine(AuCl)₂ and silver salt. The reactivity was largely dependent on the nature of the gold(I) species.     

Stereocontrolled Synthesis of syn‐β‐Hydroxy‐α‐Amino Acids by Direct Aldolization of Pseudoephenamine Glycinamide

β‐Hydroxy‐α‐amino acids figure prominently as chiral building blocks in chemical synthesis and serve as precursors to numerous important medicines. Reported herein is a method for the synthesis of β‐hydroxy‐α‐amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one‐flask protocol. Enolization of (R,R)‐ or (S,S)‐pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of LiCl followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L ‐ or D ‐threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55–98 %, and are readily transformed into β‐hydroxy‐α‐amino acids by mild hydrolysis or into 2‐amino‐1,3‐diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes.     

Lewis Acid Catalyzed Enantioselective Desymmetrization of Donor–Acceptor meso‐Diaminocyclopropanes

The first Lewis acid catalyzed enantioselective ring‐opening desymmetrization of a donor–acceptor meso‐diaminocyclopropane is reported. The copper(II)‐catalyzed Friedel–Crafts alkylation of indoles and one pyrrole with an unprecedented meso‐diaminocyclopropane delivered enantioenriched, diastereomerically pure urea products, which are structurally related to natural and synthetic bioactive compounds. The development of a new ligand through the investigation of an underexplored subclass of bis(oxazoline) ligands was essential for achieving high enantioselectivities.     

Chiral Phosphoric Acid Dual‐Function Catalysis: Asymmetric Allylation with α‐Vinyl Allylboron Reagents

We report a dual function asymmetric catalysis by a chiral phosphoric acid catalyst that controls both enantioselective addition of an achiral α‐vinyl allylboronate to aldehydes and pseudo‐axial orientation of the α‐vinyl group in the transition state. The reaction produces dienyl homoallylic alcohols with high Z‐selectivities and enantioselectivities. Computational studies revealed that minimization of steric interactions between the alkyl groups of the diol on boron and the chiral phosphoric acid catalyst influence the orientation of α‐vinyl substituent of the allylboronate reagent to occupy a pseudo‐axial position in the transition state.     

Brønsted Acid Catalyzed,Conjugate Addition of β‐Dicarbonyls to In Situ Generated ortho‐Quinone Methides—Enantioselective Synthesis of 4‐Aryl‐4H‐Chromenes

We describe herein a catalytic, enantioselective process for the synthesis of 4H‐chromenes which are important structural elements of many natural products and biologically active compounds. A sequence comprising a conjugate addition of β‐diketones to in situ generated ortho‐quinone methides followed by a cyclodehydration reaction furnished 4‐aryl‐4H‐chromenes in generally excellent yields and high optical purity. A BINOL‐based chiral phosphoric acid was employed as a Brønsted acid catalyst which converted ortho‐hydroxy benzhydryl alcohols into hydrogen‐bonded ortho‐quinone methides and effected the carbon–carbon bond‐forming event with high enantioselectivity.     

Brønsted Acid Catalyzed Addition of Enamides to ortho‐Quinone Methide Imines—An Efficient and Highly Enantioselective Synthesis of Chiral Tetrahydroacridines

The direct and highly enantioselective synthesis of tetrahydroacridines was achieved through the phosphoric acid catalyzed addition of enamides to in situ generated ortho‐quinone methide imines and subsequent elimination. This novel one‐step process constitutes a very efficient, elegant, and selective synthetic approach to valuable N‐heterocycles with a 1,4‐dihydroquinoline motif. By subsequent highly diastereoselective hydrogenation and N‐deprotection the reaction products were easily converted into free hexahydroacridines with a total of three new stereogenic centers.