β-氨基酮不对称还原反应的理论研究

本文用AM1半经验分子轨道方法,首次从热力学和动力学角度研究了(R)-4-苄基-5,5-二苯基-1,3,2口恶唑硼烷催化还原系列β-氨基酮的反应,获得了CBS 反应机理各步的反应热及第二、第四步骤的反应活化能,结果表明第二步(催化配合物的形成)和第四步(产物的形成和催化剂的释放)为吸热反应,且第四步反应吸热较多,且活化能远高于第二步,同时发现CBS反应机理中第二步为控制反应产物构型取向的决定步骤,根据第二步反应中生成R和S型催化配合物的活化能之差可推测β-氨基酮分子中羰基对位推电子基的存在有利于获得高光学活性的氨基醇产物。     

Enantioselective synthesis of (2R,3R)- and (2S,3S)-2- [(3-chlorophenyl)-(2-methoxyphenoxy)methyl]morpholine

The enantioselective synthesis of the (R,R)- and (S,S)-enantiomers of 1 from commercially available 3-chlorocinnamic acid is reported. The Sharpless asymmetric epoxidation was used to establish the stereocenters in the synthesis of both enantiomers of 1.     

Organocatalytic asymmetric total synthesis of (R)-rolipram and formal synthesis of (3S,4R)-paroxetine

An efficient enantioselective total synthesis of (R)-rolipram and an efficient enantioselective formal synthesis of (3S,4R)-paroxetine has been achieved using the highly enantioselective Michael addition of malonate nucleophiles as key steps in both cases.     

Straightforward synthesis of panaxytriol: an active component of Red Ginseng

A total synthesis of (3R,9R,10R)-panaxytriol (1) was accomplished enantioselectively (40% overall yield; 30% for the longest sequence). A key step was a Cadiot-Chodkiewicz cross-coupling reaction on two fragments containing, in the aggregate, three unprotected hydroxyl groups. One fragment was synthesized by a highly enantioselective reduction of an enynone. The other arose from a highly enantioselective dihydroxylation of an allylic alcohol.     

The kinetics of enantioselective hydrogenation of methyl acetoacetate using a modified Raney nickel catalyst

The kinetics of enantioselective hydrogenation of methyl acetoacetate using Raney nickel modified by (2R,3R)-(+)-tartaric acid were studied, thereby focusing on the effects of the reaction conditions on the enantioselectivity. Reactions were carried out in a liquid phase under atmospheric and increased hydrogen pressure. The reaction course was described by the exponential kinetics model and by Langmuir-Hinshelwood kinetics assuming the existence of two types of active sites on the catalyst surface, selective and non-selective. Using Langmuir-Hinshelwood kinetics, the acquired parameters were used for discussion of the effects of the reaction conditions on the enantioselectivity and the mechanism of the enantioselective hydrogenation.     

Enantioselective direct aminalization with primary carboxamides catalyzed by chiral ammonium 1,1'-binaphthyl-2,2'-disulfonates

A highly effective catalytic enantioselective direct aminal synthesis was developed. Chiral ammonium 1,1'-binaphthyl-2,2'-disulfonates, which were prepared in situ from (R)-BINSA and achiral amines, promoted the enantioselective addition of primary amides to aromatic aldimines.     

Study of the fluorescent properties of partially hydrogenated 1,1'-bi-2-naphthol-amine molecules and their use for enantioselective fluorescent recognition

The fluorescent properties of a series of H(8)BINOL-amine compounds are investigated. It is revealed that the intramolecular hydrogen bonds of these compounds contribute to the shift of the emission of their H(8)BINOL unit to a much longer wavelength. That is, the emission of H(8)BINOL is at λ = 323 nm, but that of the H(8)BINOL-amino alcohol (S)-5 is at λ = 390 nm. Binding of (S)-5 with mandelic acid suppresses its intramolecular hydrogen bonding and restores the short wavelength emission of the H(8)BINOL unit. When (S)-5 (1.0 × 10(-4) in CH(2)Cl(2)) was treated with (R)-mandelic acid (4.0 × 10(-3)), a large fluorescence enhancement at the short wavelength (λ(emi) = 330 nm) was observed with I(R)/I(0) = 11.7. When (S)-MA was used under the same conditions, the enhancement at the short wavelength emission was much smaller. Thus, a good enantioselective fluorescent response was observed with ef =3.5 [ef: enantioselective fluorescence enhancement ratio = (I(R) - I(0))/(I(S) - I(0))]. This study demonstrates that the H(8)BINOL-based molecules are promising as a new class of enantioselective fluorescent sensors.     

Synthesis of rare earth catalysts and their applications for enantioselective synthesis of heterocyclic β-amino alcohols

A new family of chiral lanthanide complexes derived from (R)-binaphthol has been synthesized by a one-pot procedure using only commercially available substrates. These complexes were evaluated for the aminolysis of meso-epoxides and proved to be efficient enantioselective catalysts. The samarium complex coordinated by two (R)-binaphthoxide ligands was the most enantioselective catalyst of this series. β-Amino alcohols including heterocycles have been isolated with enantiomeric excesses up to 84%.     

Unprecedented oxidation of a phenylglycinol-derived 2-pyridone: enantioselective synthesis of polyhydroxypiperidines

[reaction: see text]. The phenylglycinol-derived 2-pyridone 1 undergoes m-CPBA oxidation steroselectively leading to the chiral nonracemic unsaturated bicyclic hydroxylactam 2, from which the enantioselective synthesis of (3R,5R)-3,4,5-trihydroxypiperidine (16) and the formal synthesis of the azasugar epiisofagomine are described. The enantioselective synthesis of (S)-N-Boc-3-hydroxypiperidine and (3R,4S)-3,4-dihydroxypiperidine is also reported.     

Asymmetric iodocyclization catalyzed by salen-CrIIICl: its synthetic application to swainsonine

The previously developed enantioselective iodocyclization of gamma-hydroxy-cis-alkenes required 30 mol% of (R,R)-salen-Co(II) complex as chiral catalyst and 0.75 equivalent of N-chlorosuccinimide (NCS) as activator to produce 2-substituted tetrahydrofurans with 61 to 90% ee. Due to the considerable loading amount of the Co(II) complex, another more effective catalyst was pursued by screening (R,R)-salen-transition metal complexes. When 10 mol% of the catalysts were applied with 0.5 equivalent of NCS, a higher level of stereoselectivity was attained with the corresponding Cr(III)Cl (84% ee), Mn(II)Cl (52% ee) and Co(II) complexes (66% ee). Refinement of the conditions established a novel catalytic enantioselective iodocyclization protocol using iodine in the presence of 7 mol% of (R,R)-salen-Cr(III)Cl complex activated by 0.7 equivalent of NCS in toluene to induce 74 to 93% ee.     

铱(I)苯乙胺Schiff碱络合物催化苯乙酮的不对称氢转移反应

以光学活性的苯乙胺和吡啶－２－甲醛缩合而得到的Ｓｃｈｉｆ碱（ＰＰＥＩ）（ＰＰＥＩ＝２－［［Ｎ－（１－ｐｈｅｎｙｌｅｔｈｙｌ）ｉｍｉｎｏ］ｍｅｔｈｙｌ］ｐｙｒｉｄｉｎｅ或２－［［Ｎ－（１－苯乙基）亚胺］甲基］吡啶）为配体，进而与［Ｉｒ（ＣＯＤ）Ｃｌ］２（ＣＯＤ＝１，５－环辛二烯）反应，合成了８个光学活性铱络合物，考察了它们在异丙醇存在下催化苯乙酮不对称氢转移反应的光学活性，发现［Ｉｒ（ＣＯＤ）（ＰＰＥＩ）Ｉ］具有较好的立体选择性．其光学产率最高可达３５．７％ｅ．ｅ．．     

Enantioselective chromenone benzoxazole receptor for glutamic acid and its derivatives

Combination of a binaphthyl unit with chromenone benzoxazole fragments provided a chiral receptor that is enantioselective for glutamic acid and its derivatives. The receptor racemic mixture was resolved by TLCs impregnated with (R,R)-thiodilactic acid. High association constants were measured for dansylglutamic acid, using a fluorescent method. This receptor can be used for the resolution of the tosylglutamic acid racemic mixture.     

Total synthesis of (+)-trans-195A

[reaction: see text] The first enantioselective synthesis of (+)-trans-195A is described. The structure has been constructed by ring-rearrangement metathesis (RRM) and zirconium-mediated Negishi-coupling, used for the first time to prepare 6,6-membered heterocycles, as key steps. By comparison of the synthesized material with the isolated natural product, the absolute configuration of natural trans-195A was determined to be (2R,4aS,5R,8aS)-(-).     

Facile enantioseparation and recognition of mandelic acid and its derivatives in self‐assembly interaction with chiral ionic liquids

Mandelic acid and its derivatives are important medical intermediates in the pharmaceutical industry. Different stereoisomers exhibited distinct biological properties to human bodies. Given that, enantioselective recognition and separation of mandelic acid are of great importance. In this study, four novel different types of chiral ionic liquids bearing designed functional groups were synthesized and successful enantioselective precipitation with mandelic acid and its derivatives. That is, (R, R)‐chiral ionic liquid 1 can coprecipitated with S‐mandelic acid and its derivatives was observed. In addition, good correlation coefficient is achieved by using electrospray mass spectrum at negative ion pattern for quick analysis of the enantioselective precipitation, which could be served as a method of enantioselective recognition. The possible intermolecular interactions are established after systematical studies by NMR spectroscopy and DFT calculations.     

Function of an N-heterocyclic carbene ligand based on concept of chiral mimetic

Function of a new N-heterocyclic carbene ligand based on the concept of a chiral mimetic is described. With (4R,5R)-4,5-diphenyl-1,3-dialkyl-4,5-dihydro-3H-imidazol-1-ium tetrafluoroborates as N-heterocyclic carbene precursors, Rh-catalyzed enantioselective arylation (up to 27% ee) of aromatic aldehydes with arylboronic acids and Pd-catalyzed enantioselective intramolecular alpha-arylation (up to 66% ee) of N-(2-bromoaryl)-N-alkyl-2-arylpropanamides are investigated.     

Highly enantioselective synthesis of 2,6-disubstituted and 2,2,6-trisubstituted dihydropyrones: a one-step synthesis of (R)-(+)-hepialone and its analogues

An efficient enantioselective approach to chiral dihydropyrones has been developed by the hetero-Diels-Alder (HDA) reactions of (E)-4-methoxy-2-trimethylsiloxy-penta-1,3-diene (diene 1) with aldehydes and pyruvates. It has been found that the readily accessible (R)-BINOL-Ti(OiPr)(4) (1.1:1) complex was a very effective catalyst for this reaction. Aromatic, heteroaromatic, conjugated, and aliphatic aldehydes afforded the corresponding products in moderate to high isolated yields (up to 99%) with excellent enantioselectivities (up to 99% ee). The first example of highly enantioselective synthesis of 2,2,6-trisubstituted dihydropyrones by the catalytic reaction of diene 1 with pyruvates was reported. The isolated intermediates indicated that this asymmetric HDA reaction proceeded in a Mukaiyama aldol pathway. On the basis of the absolute configurations of the products, a possible mechanism was proposed. Moreover, the catalytic system could be used to synthesize a series of enantioenriched beta-hydroxyketones 4. Finally, this methodology was successfully applied for the one-step synthesis of the important natural product (R)-(+)-Hepialone with 88% isolated yield and 94% enantioselectivity.     

Unexpected change of the sense of the enantioselective hydrogenation of ethyl pyruvate catalyzed by a Pt-alumina-cinchona alkaloid system

In the enantioselective hydrogenation of ethyl pyruvate (EtPy) over beta-isocinchonine (beta-ICN) modified Pt-alumina catalysts, the major enantiomer was (R)-ethyl lactate ((R)-EtLt (ee 50%)) in toluene, while in AcOH (S)-EtLt (ee 60%) was formed; the (R) configuration is opposite to what is expected from the absolute configuration of the cinchonine backbone.     

(2R，3R)-和(2S，3S)-2-(4-羟基-3-甲氧基)-3-羟甲基-1，4-苯并二氧六环-6-醛的对映选择性合成

1,4-苯并二氧六环木脂素类天然产物多数具有增加胆碱乙酰化酶和抗肝毒等活性 ,其活性主要源于 1 ,4-苯并二氧六环官能团 [1] . 1 ,4-苯并二氧六环木脂素的消旋全合成已有报道 [2 ] ,但其不对称合成还是空白[3] .我们发展了一条对映选择性合成 1 ,4-苯并二氧六环木脂素的简捷有效的路线 .基于前面的工作 [4 ] ,我们发现 1 ,4-苯并二氧六环醛类衍生物是合成此类天然产物的关键中间体 ,选择 2 - (4-羟基- 3-甲氧基 ) - 3-羟甲基 - 1 ,4-苯并二氧六环 - 6-醛 (1 )作为目标分子 ,其合成路线如下 :Reagents and conditions:( ) Me OH,H2 SO4,9…     

Synthesis and highly enantioselective hydrogenation of exocyclic enamides: (Z)-3-arylidene-4-acetyl-3,4-dihydro-2H- 1,4-benzoxazines

Highly enantioselective hydrogenation of exocyclic enamides, (Z)-3-arylidene-4-acyl-3,4-dihydro-2H-benzoxazines, was achieved in up to 98.6% ee by using Rh/(R,R)-Me-Duphos complex as the catalytic system. The absolute configuration of the product was assigned as R by chemical interrelations.     

Catalytic enantioselective fluorination of oxindoles

We have developed a highly efficient catalytic enantioselective fluorination of oxindole derivatives. In the presence of a catalytic amount of chiral Pd complex 2 (2.5 mol %), various substrates, including aryl- and alkyl-substituted oxindoles, were fluorinated in a highly enantioselective manner (up to 96% ee). In addition, when R was a hydrogen atom, enantioselective fluorination followed by solvolysis gave a monofluorinated ester with up to 93% ee. To our knowledge, this is the first example of catalytic enantioselective fluorination of oxindoles.