Asymmetric halolactonisation reaction—1 : Asymmetric synthesis of optically active α,α-disubstituted-α-hydroxy acids from α,β-unsaturated acids by the novel use of halolactonisation r

Considering the usefulness of optically active α,α-disubstituted -α -hydroxy acids (1) andα,α- disubstituted-α-hydroxy ketones (2) readily accessible from 1 exploitation of a new asymmetric synthesis of 1 from α,β-unsaturated acids (3) which utilised halolactonisation reaction as its key step, was studied.The asymmetric bromolactonisation of (S) N-(α, β-unsaturated)acylproline((S) 5) derivable from 3 such as tiglic acid (3a) and trans-α methylcinnamic acid (3b), with N-bromosuccinimide in N,N dimethylformamide was found to proceed in a highly stereoselective and regiospecific manner giving a mixture of the two diastereomeric bromolactones (8) in which one diastereomer (8A) was highly predominant. Debromination of 8 followed by acidic hydrolysis readily afforded (R)-1 being 89-98% optically pure.     

A novel facet of the halolactonisation reaction

Steric versus acidity-controlled change during lactonisation of monosubstituted maleic anhydride-cyclopentadiene adducts has been studied to eliminate some confusion in the literature arising from the use of limited information. The transannular lactonisation of proximately aligned, yet dissymmetric, dicarboxylic acid is controlled under acidic conditions by bulk effects and under basic conditions by pK_a, effects.     

Asymmetric halolactonisation reaction—4: Asymmetric synthesis of optically active α,β-epoxyaldehydes from α,β-unsaturated acids

The bromolactones (5) stereoselectively produced by the asymmetric bromolactonisation of (S)-N-(α,β-unsaturated) acylprolines(3), were elaborated to highly optically active 2(R),3(S)-epoxyaldehydes(8)(84–98% ee) by successive epoxide formation and reductive cleavage of the proline moiety. The overall process constitutes a highly efficient asymmetric synthesis of 8 from α,β-unsaturated acids(1).     

Elucidating the mechanism of the asymmetric aza-Michael reaction

The mechanism of the palladium-catalysed asymmetric aza-Michael addition of aniline to alpha,beta-unsaturated N-imide was examined from several aspects using a combination of techniques, including X-ray crystallography, mass spectrometry, NMR, UV/Vis spectroscopy, and kinetic studies. The binding of aniline to the dicationic palladium(II) metal centre was found to occur in two consecutive steps: The binding of the first aniline is fast and reversible, whereas the binding of the second aniline is slower and irreversible. This occurs in competition with the binding of the N-imide, which forms a planar six-membered chelate ring with the metal centre; coordinating through the 1,3-dicarbonyl moiety. Isotopic labelling revealed that the addition of N-H occurs in a highly stereoselective manner, allowing the synthesis of optically active beta(2)- and beta(2,3)-amino acid derivatives. The stereochemistry of the addition is postulated to be syn. In situ kinetic studies provided evidence for product inhibition. The binding of the N-imide to the catalyst was found to be the rate-limiting step. Aniline was found to be an inhibitor of the pre-catalyst. The study culminated in the design of a new reaction protocol. By maintaining a low concentration of the aniline substrate during the course of the reaction, significant enhancement of yield and enantioselectivity can be achieved.     

Elucidation of the reaction mechanism for the synthesis of ZnGeN2 through Zn2GeO4 ammonolysis

Ternary II–IV–N₂ materials have been considered as a promising class of materials that combine photovoltaic performance with earth-abundance and low toxicity. When switching from binary III–V materials to ternary II–IV–N₂ materials, further structural complexity is added to the system that may influence its optoelectronic properties. Herein, we present a systematic study of the reaction of Zn₂GeO₄ with NH₃ that produces zinc germanium oxide nitrides, and ultimately approach stoichiometric ZnGeN₂, using a combination of chemical analyses, X-ray powder diffraction and DFT calculations. Elucidating the reaction mechanism as being dominated by Zn and O extrusion at the later reaction stages, we give an insight into studying structure–property relationships in this emerging class of materials.

Combining chemical analyses with detailed structural work, we decipher the reaction pathway in the ammonolysis of Zn₂GeO₄ towards ZnGeN₂.     

Stereochemistry of the halolactonisation reaction The reaction of cis- and trans- stilbene-2-carboxylic acids with halogens

The stereochemistry of the reaction of cis- and trans-stilbene-2-carboxylic acids with chlorine and bromine, yielding the two diastereoisomeric 3-phenyl-4-halo-3:4-dihydroisocoumarins (III) and (IV) has been investigated. The reactions are entirely stereospecific and involve intramolecular attack by the carboxyl group on an intermediate carbonium or halonium ion. The lactones (III) and (IV) yield the two 3-(-hydroxybenzyl) phthalides (V) and (VI), with retention of configuration. Thionyl chloride transforms (V) and (VI) into the 3-(-chlorobenzyl) phthalides (IX) and (X), with inversion. Steric effects are mainly responsible for the alternative formation of halolactones or normal dihalogenated derivatives in the reactions between unsaturated acids and halogens.     

过氧化物酶在不对称氧化中的应用及氧化反应机理

过氧化物酶尤其是从Caldariomyces fumago中得到的氯过氧化物酶（GPO）能 催化多种底物的氧化和环氧化反应，表现出良好的立体选择性，近年在此领域内的 应用有若干重要的进展。由于CPO与细胞色素P450单加氧酶的相似性，它们的反应 机理与活性部位的研究也十分引人瞩目。     

Asymmetric total synthesis of (-)-laulimalide: exploiting the asymmetric glycolate alkylation reaction

A concise total synthesis of the potent antitumor macrolide (-)-laulimalide is described. The observation that homoallylic (or latent homoallylic) C-O bonds are present at C5, C9, C15, C19, and C23 led to the strategic decision to rely heavily on the asymmetric glycolate alkylation to construct both the C1-C14 fragment 3 and the C15-C27 subunit 4. A diastereoselective addition of a C1-C14 allylstannane to a C15-C27 alpha,beta-epoxyaldehyde served to join the two advanced fragments. A Mitsunobu macrolactonization of hydroxy acid 2 avoided isomerization of the sensitive 2,3-Z-enoate, which has been observed in base-catalyzed macrolactonizations. Removal of two TBS protecting groups to reveal the C15 and C20 hydroxyls occurred without rearrangement to isolaulimalide.     

Asymmetric synthesis of polyhydroxy alpha-amino acids with the sulfinimine-mediated asymmetric strecker reaction: 2-amino 2-deoxy L-xylono-1,5-lactone (polyoxamic acid lactone)

Polyhydroxylated sulfinimines derived from protected 1,2-O-isopropyliden-L-threoses undergo the sulfinimine-mediated Strecker syntheses to give alpha-amino nitriles in good yield and de. A double stereodifferentiation effect was not observed and the diastereoselectivity is controlled by the absolute configuration of the sulfinyl group. Hydrolysis of the amino nitriles afforded the lactone rather than polyoxamic acid.     

Elucidation of the mechanism of the reaction between phenylboronic acid and a model diol, Alizarin Red S

In this work, the reaction between phenylboronic acid and the diol-containing, fluorescent dye Alizarin Red S (ARS) was probed. Fluorescence titrations, (11)B NMR measurements, and both pre- and steady-state kinetic experiments were used for the characterization of this reaction over a large pH range (4-10.5). It was shown that ARS preferentially reacted with the boronic (neutral, trigonal) form of phenylboronic acid; however, the boronate (anionic, tetrahedral) form was also reactive. All in all, four reactant species were implicated in the formation of four different adduct species. The rate of a given adduct formation depended on the combination of the solution pH and the pK(a)'s of both ARS and the arylboronic acid. The reaction was found to proceed in two distinct kinetic steps with the products and starting materials in facile exchange. In addition, the elucidation of the mechanism indicated the presence of two fluorescent products with the structure of the major contributor differing from what had been cited in the literature.     

Asymmetric synthesis of a chiral arsinophosphine via a metal template promoted asymmetric Diels-Alder reaction between diphenylvinylphosphine and 2-furyldiphenylarsine

The asymmetric Diels-Alder reaction between 2-furyldiphenylarsine and diphenylvinylphosphine was achieved stereospecifically by utilizing an organoplatinum reaction promoter containing the ortho-metalated (R)-(1-(dimethylamino) ethyl)-naphthalene as the chiral auxiliary. The optically pure (+)-As-P heterobidentate cycloadduct could be liberated from the template product by successive treatment with concentrated hydrochloric acid and aqueous potassium cyanide.     

A bifunctional rosin-derived thiourea catalyzed asymmetric tandem reaction and its new mechanism

A direct asymmetric tandem reaction of a-nitro ketones with b g-unsaturated a-ketoesters was found to be catalyzed by a bifunctional rosin-derived thiourea and gave 5-nitro-2-actoxyl-2-pentenates in excellent ee values and yields,a much better result than previously reported.Furthermore,through theoretical analysis,literature research and experimental verifications,a new mechanism involving an inverse-electron-demand Diels–Alder(IEDDAR) and a retro-Henry reaction was proposed.     

Hydrogen-bond-mediated asymmetric cascade reaction of stable sulfur ylides with nitroolefins: scope, application and mechanism

A hydrogen-bond-mediated asymmetric [4+1] annulation/rearrangement cascade of stable sulfur ylides and nitroolefins was developed. This reaction provides a facile route to enantioenriched 4,5-substituted oxazolidinones in moderate to excellent isolated yields (65-96?%) with excellent stereocontrol (up to more than 95:5 d.r. and 97:3 e.r.). This methodology was successfully applied to the concise synthesis of two bioactive molecules. The stereocontrolled modes and mechanism have been proposed to explain the origin of this stereochemistry.     

Combining prolinamides with 2-pyrrolidinone: Novel organocatalysts for the asymmetric aldol reaction

Peptides and especially prolinamides have been identified as excellent organocatalysts for the aldol reaction. The combination of prolinamides with derivatives bearing the 2-pyrrolidinone scaffold, deriving from pyroglutamic acid, led to the identification of novel organocatalysts for the intermolecular asymmetric aldol reaction. The new hybrids were tested both in organic and aqueous media. Among the compounds tested, 22 afforded the best results in petroleum ether, while 25 afforded the products in brine in high yields and selectivities. Then, various ketones and aldehydes were utilized and the products of the aldol reaction were obtained in high yields (up to 100%) with excellent diastereo- (up to 97:3 dr) and enantioselectivities (up to 99% ee).     

催化不对称反应新发展: 不对称活化

介绍了催化不对称催化反应中的一个新概念－不对称活化(asymmetricactivation)及其研究的最新发展。运用不对称活化策略,一个光学活性的整或者甚至外消旋的催化剂可以被另一种手性活化剂(chiralactivator)选择性的活化,从而催化反应生成非外消旋产物。该方法较不对称活化(asymmetricactivation)方法的优点是被活化的催化剂能够产生较使用光学纯催化剂更高对映体过量的产物。