非螯合型手性双膦/钌催化的不对称氢化反应

对RuCl₃和手性双膦(2S,5S)-2,5-双-(二苯膦)-1,4∶3,6-双脱水-2,5-双去氧-L-艾杜醇(BDPI)催化的不对称氢化反应进行了研究,反应的转化率为100%,光学收率受[双膦]/[RuCl₃]比值的影响较大.在α-乙酰胺基肉桂酸的催化氢化反应中,[双膦]/[RuCl₃]=2.0时e.e.值最大,为68%;对衣糠酸的催化氢化,[双膦]/[RuCl₃]=3时e.e.值最大,为92%.     

Studies on the identification and syntheses of insect pheromones: XX. Synthesis of (7R, 8S)-(+)-sex pheromone of gypsy moth through the kinetic resolution of (±) allylic alcohol by Sharpless asymmetric epoxidation

The chiral epoxy alcohol 3 was synthesized in 92% e.e through the kinetic resolution of (±)-l-tridecen-3-ol 2 by Sharpless asymmetric epoxidation. 3 was then transformed to (7R, 8S)-1a, the sex pheromone of gypsy moth, in an overall yield of 60% in 5 steps.     

手性膦酸二酯类化合物的合成与结构

手性呋喃酮1a1b与亚磷酸三酯2a2b通过串联的不对称Michael加成/分子内Michalis-Arbazov重排反应,得到含磷官能团的新手性化合物5-(S)-(1S)-冰片氧基-4-膦酸二酯基-3-卤素-2(5H)-呋喃酮(3a～3d).该反应具有条件温和,产率高(69%～93%),光学纯度单一(d.e.≥98%)等特点.通过元素分析,IR,UV¹HNMR¹³CNMR,MS,[α]_D²⁰等分析数据以及X射线四圆衍射确定了它们的化学结构和绝对构型.     

Asymmetric Synthesis of Potential Precursors of the HIV Drug MC1220 and Its Analogues by Hydrogenation of (1‐Arylvinyl)pyrimidines

Because MC1220 is a promising microbicide with anti‐HIV‐1 activity, the possibility for asymmetric synthesis of its potential precursors is explored. Here, we investigate asymmetric reduction of the vinyl double bond of 6‐(1‐arylvinyl)pyrimidine derivatives to their corresponding ethylidene analogues. Catalysts with ligands bearing trivalent phosphorus ligating the soft metals rhodium(I), ruthenium(II), or iridium(I) are used for asymmetric reduction of the vinyl derivatives 5a – e . The enantioselective reduction reaches 92% ee and about 71% conversion for reduction of the 6‐(1‐(3,5‐dimethylphenyl)vinyl)pyrimidine derivative 5b using the asymmetric catalyst catASium M(R)Rh ( 7m ). However, for the more sterically hindered double bond in the corresponding 2,6‐difluorophenyl derivative 5e , the enantioselective reduction dropped to 30% ee and 14% conversion.     

Zinc-Catalyzed Asymmetric Formal [4+3] Annulation of Isoxazoles with Enynol Ethers by 6π Electrocyclization: Stereoselective Access to 2H-Azepines

6π electrocyclization has attracted interest in organic synthesis because of its high stereospecificity and atom economy in the construction of versatile 5–7-membered cycles. However, examples of asymmetric 6π electrocyclization are quite scarce, and have to rely on the use of chiral organocatalysts, and been limited to pentadienyl-anion- and triene-type 6π electrocyclizations. Described herein is a zinc-catalyzed formal [4+3] annulation of isoxazoles with 3-en-1-ynol ethers via 6π electrocyclization, leading to the site-selective synthesis of functionalized 2H-azepines and 4H-azepines in good to excellent yields with broad substrate scope. Moreover, this strategy has also been used to produce chiral 2H-azepines with high enantioselectivities (up to 97:3 e.r.). This protocol not only is the first asymmetric heptatrienyl-cation-type 6π electrocyclization, but also is the first asymmetric reaction of isoxazoles with alkynes and the first asymmetric catalysis based on ynol ethers.     

Optically active phenanthrolines in asymmetric catalysis. IV. Enantioselective hydrosilylation of acetophenone by rhodium/chiral alkyl phenanthroline catalysts.

The in situ catalysts prepared from [Rh(Cod)Cl]₂ (Cod = 1,5-cyclooctadiene) and chiral alkylphenanthroline ligands 1–6 display a remarkable activity in the asymmetric hydrosilylation of acetophenone affording, after hydrolysis, the expected 1-phenylethanol in high yield and complete selectivity. High enantioselectivities, up to 76%, were obtained in the presence of 2-substituted derivatives 5 and 6, whereas 3-alkylphenanthrolines 1–4 gave e.e.'s not higher than 6%. High chemical yields, but modest enantioselectivities (10–20% e.e.) were recorded with the potentially terdentate ligands 7–10. Chiral alkylphenanthrolines were poorly efficient ligands in the asymmetric Ni-catalysed cross-coupling of -methylbenzylmagnesium chloride with vinyl bromide.     

Simple synthesis of all of the four stereoisomers of 5-hydroxy-4-decanolide (l-factors), the proposed autoregulators from streptomyces griseus

All of the four possible stereoisomers (ca. 95 % e.e.) of 5-hydroxy-4-decanolide (L-factors), the proposed autoregulator from $\text{Streptomyces griseus}$, were synthesized from (±)-1-octen-3-ol in two or four steps employing the Sharpless asymmetric epoxidation as the keystep.     

Zinc‐Catalyzed Asymmetric Formal [4+3] Annulation of Isoxazoles with Enynol Ethers by 6π Electrocyclization: Stereoselective Access to 2H‐Azepines

6π electrocyclization has attracted interest in organic synthesis because of its high stereospecificity and atom economy in the construction of versatile 5–7‐membered cycles. However, examples of asymmetric 6π electrocyclization are quite scarce, and have to rely on the use of chiral organocatalysts, and been limited to pentadienyl‐anion‐ and triene‐type 6π electrocyclizations. Described herein is a zinc‐catalyzed formal [4+3] annulation of isoxazoles with 3‐en‐1‐ynol ethers via 6π electrocyclization, leading to the site‐selective synthesis of functionalized 2H‐azepines and 4H‐azepines in good to excellent yields with broad substrate scope. Moreover, this strategy has also been used to produce chiral 2H‐azepines with high enantioselectivities (up to 97:3 e.r.). This protocol not only is the first asymmetric heptatrienyl‐cation‐type 6π electrocyclization, but also is the first asymmetric reaction of isoxazoles with alkynes and the first asymmetric catalysis based on ynol ethers.     

Asymmetric autocatalysis of pyrimidyl alkanol and related compounds. Self-replication,amplification of chirality and implication for the origin of biological enantioenriched chirality

We discovered asymmetric autocatalysis in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde, where the product 5-pyrimidyl alkanol acts as a highly efficient asymmetric autocatalyst to afford more of itself (Soai reaction). Asymmetric autocatalysis proceeded quantitatively (>99% yield), affording itself as a near enantiomerically pure (>99.5% ee) product. An extremely low enantiomeric excess (ca. 0.00005% ee) can automultiply during three rounds of consecutive asymmetric autocatalysis to >99.5% ee by asymmetric amplification. Circularly polarized light, and inorganic and organic crystals, act as the origin of chirality to trigger asymmetric autocatalysis. Asymmetric autocatalysis has enormous power to recognize and amplify the chirality of hydrogen, carbon, oxygen, and nitrogen isotopomers. Moreover, absolute asymmetric synthesis, i.e., the formation of enantioenriched compounds without the intervention of any chiral factor, is realized by asymmetric autocatalysis. By using designed molecules based on 5-pyrimidyl alkanol, the intramolecular asymmetric control, self-replication, and improvement of chiral multifunctionalized large molecules has been developed by applying asymmetric autocatalysis.     

Spontaneous symmetry breaking in the formation of a dinuclear gadolinium semiquinonato complex: synthesis, high-field EPR studies, and magnetic properties

The synthesis and characterisation of an asymmetric dinuclear gadolinium(III) semiquinonato complex, namely [Gd2(HBPz3)2(dtbsq)4] CHCl3 (1; HBPz3 = hydrotris(pyrazolyl)borate, dtbsq = 3,5-di-tert-butyl-O-semiquinone), is reported. The crystal structure of 1 was determined at room temperature. It crystallises in the triclinic system P1, with a = 16.735(5) A, b = 17.705(5) A, c = 19.553(5) A, alpha = 99.680(5) degrees, beta = 109.960(5), gamma = 107.350(5) degrees, Z = 2 and R = 9.96. The structure of 1 consists of a dinuclear asymmetric unit in which the two gadolinium(III) ions have coordination numbers of eight and nine. Three of the dioxolene molecules act as asymmetric bridging ligands, while the fourth molecule behaves as a bidentate ligand towards a single metal ion. The magnetic properties of 1 were investigated by means of susceptibility measurements and high-field electron paramagnetic resonance (HF-EPR) spectroscopy. They revealed an S = 0 ground spin state with excited states of higher spin very close in energy and a small negative zero-field splitting with a transverse anisotropy term for a S = 7 state.     

Expeditious synthesis of a key C9–C21 subunit of the aplyslatoxine and oscillatoxins

The C₉–C₂₁ portion of the aplysiatoxin/oscillatoxin bluegreen algal metabolites was synthesized as the 9-aldehyde bearing a tert-butyldimethylsilyl ether group on the C₁₁ hydroxyl and a trimethylsilylethoxymethyl ether group on the C₂₀ hydroxyl. Featuring an asymmetric aldol and an asymmetric oxazaborolldine reduction, the synthesis proceeded with high (>90%) stereoselectivity in 13 steps and 5–7% overall yield from commercial starting material.     

Catalytic asymmetric borane reduction of prochiral ketones using chiral camphor-derived mercapto-alcohols

Easily available D-(+)-camphor-derived chiral mercapto-alcohols 2 and 3 were employed for catalytic asymmetric borane reduction of aromatic ketones. Moderate enantioselectivities with e.e. 20.2-72.1% were obtained with 10 mol% catalyst. Opposite asymmetric induction was achieved when mercapto-alcohols 2 and 3 were used.     

对位取代的1,2-二苯基乙烯的合成及其不对称二羟基化反应

近年来,人们对催化不对称二羟基化反应进行了广泛和深入的研究.前文曾报道了邻位取代的(E)-1,2-二苯乙烯的不对称二羟基化反应.本文探讨了对位取代的(E)-1,2-二苯乙烯类化合物的合成.     

Synthesis of the enantiomers of cis-2-methyl-5-hexanolide,the major component of the sex pheromone of the carpenter bee

(2R,5S)-2-Methyl-5-hexanolide and its antipode were synthesized in highly optically pure state (?98–99% e.e.) starting from ethyl (S)-lactate and the enantiomers of methyl β-hydroxyisobutyrate. The specific rotations of our samples were [α]_D±91.0-93.5° (CHCl₃), while the reported values of the samples prepared by resolution or asymmetric synthesis were ±64.5–65.6°.     

Cytotoxicity of asymmetric platinum complexes against L-1210 cells. Effect of bulky substituents

The asymmetric platinum complexes cis-Pt(LL')Cl2 (L = NH3, L' = CH3NH2, (CH3)2NH, C2H5NH2 and (C2H5)2NH and LL' = N,N-dimethylethylenediamine),--one of the NH3 groups of cis-Pt(NH3)2Cl2 was substituted by alkylamine--, were synthesized and their cytotoxic effects have been measured using L-1210 cells. The IC50 values of the asymmetric platinum complexes,--being obtained after 24 h exposure of L-1210 cells to the platinum complexes--, are almost comparable to the corresponding value of cis-Pt(NH3)2Cl2. In 2 h exposure, however, the IC50 values of the platinum complexes were dramatically changed, i.e., a marked difference was observed between those of L' = RNH2 and L' = R2NH. On the other hand, the amounts of platinum taken into the L-1210 cells is little affected by the alkylamino substitution. The results suggest that the bifunctional platinum binding to the target molecule may be responsible for the cytotoxicity.     

Reduction of carbonyl compounds via hydrosilylation: V. Synthesis of optically active allylic alcohols via regioselective asymmetric hydrosilylation

Regioselective asymmetric reduction of prochiral α,β-unsaturated ketones to optically active allylic alcohols was performed via hydrosilylation catalyzed by a rhodium(I) complex with (+)-BMPP, (+)-DIOP and (?)-DIOP as chiral ligands. The allylic alcohols with optical purity up to 69% e.e. were obtained in good yields. The extent of asymmetric induction was found to depend on the stereo-electronic matching of the chiral ligand, ketone and hydrosilane employed. In the asymmetric reduction of (R)-carvone, leading to carveol, the extent of asymmetric induction was found to depend markedly on the ligand/rhodium ratio. Either trans-(5R,1S)-carveol or cis-(5R,1R)-carveol was obtained with good stereoselectivity by using (?)-DIOP or (+)-DIOP as chiral ligand, and it turned out that the chiral center present in carvone had only a slight influence on the asymmetric induction by the chiral catalysts.     

Asymmetric synthesis of the cis- and trans-stereoisomers of 4-aminopyrrolidine-3-carboxylic acid and 4-aminotetrahydrofuran-3-carboxylic acid

The diastereoselective conjugate addition of lithium (S)-N-benzyl-N-[small alpha]-methylbenzylamide has been successfully applied to the first asymmetric syntheses of cis-(3S,4R)- and trans-(3R,4R)-4-aminotetrahydrofuran-3-carboxylic acids (26% and 25% overall yield respectively, >98% d.e. and >97% e.e. in each case). Furthermore, the most efficient asymmetric synthesis to date of cis-(3R,4R)- and trans-(3R,4S)-4-aminopyrrolidine carboxylic acids is delineated: for cis-(3R,4R), four steps, >98% d.e., 52% overall yield; for trans-(3R,4S), five steps, >98% d.e., 50% overall yield.     

芳香酮的高效对映选择性转移氢化

手性芳香醇在制药工业上有重要的应用,因而利用芳香酮的对映选择性氢化制备相应的手性醇已引起人们极大关注.近10年来,用手性金属配合物为催化剂,利用种种有机物作氢源,实现芳香酮的不对称氢转移氢化取得了很大进展.但这些反应过程的催化活性仍然较低,底物酮与催化剂.     

Asymmetric Synthesis XI: Stereoselective Synthesis of α-Alkyl-2-Furfurylamines Via d-Camphor Ketimine Intermediate

(R)-α-alkyl-2-furfurylamines (7), ranging from 5–67%d.e., are obtained by asymmetric alkylation of d-camphor ketimine (3). Using 1,3-diiodopropane and dibromoxylene as alkylating reagents, diimine derivatives (6f) and (6g) are formed. However, 1,2-dibromoethane gives coupling product (6h).     

Asymmetric Hydroboration of 1,1‐Disubstituted Alkenes

A breakthrough in the asymmetric hydroboration of notoriously difficult 1,1‐disubstituted alkenes using a new family of highly effective hydroboration reagents is described (see scheme). The intermediate boranes can be oxidized to alcohols or used in Suzuki–Miyaura cross‐coupling reactions.