A dirhodium(II)-carbenoid route to (-)- and (+)-Geissman-Waiss lactone: synthesis of (1R,7R,8R)-(-)-turneforcidine.

(-)- and (+)-Geissman-Waiss lactone, 4b, was efficiently prepared via the intramolecular C-H insertion reaction of the chiral nonracemic diazoacetates (-)-5a and (+)-5b catalyzed by dirhodium(II) tetrakis[methyl (5R and 5S)-3-phenylpropanoyl-2-imidazolidinone-5-carboxylate]. The cyclization was found to proceed with excellent regioselectivity and cis-diastereoselectivity. The bicyclic lactone (-)-4b was successfully used in the synthesis of the necine base, (-)-turneforcidine 2.     

Totally selective synthesis of enantiopure (3S,5S)- and (3R,5R)-4-amino-3,5-dihydroxypiperidines from aminodiepoxides derived from serine

The transformation of enantiopure (2R,4R)- and (2S,4S)-N,N-dibenzyl-1,2:4,5-diepoxypentan-3-amine, 1 and 2, into the corresponding enantiopure (3S,5S)- and (3R,5R)-3,5-dihydroxy-3-aminopiperidines, 3 and 4 respectively, is described. The opening of the two epoxide rings with a range of amines takes place with total regioselectivity and high yields, in the presence of LiClO4. A mechanism to explain this transformation is proposed.     

(Z)-3-p-tolylsulfinylacrylonitriles as chiral dipolarophiles: reactions with diazoalkanes

[reaction: see text] The dipolarophilic reactivity of enantiopure (Z)-3-p-tolylsulfinylacrylonitriles (1) has been evaluated with diazoalkanes. 3-Cyanopyrazoles are obtained when R = H, but with R = alkyl (Bn, n-Bu, and t-Bu) only one cycloadduct (4 or 5) is formed in high yield under mild conditions, therefore evidencing a complete control of the regioselectivity and the endo/exo and pi-facial selectivities. These reactions are a new straightforward entry to the synthesis of pyrazolines and related structures and reveal the excellent dipolarophilic features of (Z)-sulfinylacrylonitriles.     

Synthesis and Crystal Structure of Ethyl 1-（2-bromoethyl）-3-（4-meth-oxyphenyl）-1H-pyrazole-5-carboxylate

The title compound ethyl 1-(2-bromoethyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate 1 has been synthesized and structurally characterized by single-crystal X-ray diffraction.The crystal is of monoclinic(C15H17BrN2O3,Mr = 353.22),space group C21 with a = 24.691(7),b = 6.7678(17),c = 17.884(5) ,β = 97.184(5)o,V = 2965.1(13) 3,Z = 8,Dc = 1.583 g.cm-3,F(000) = 1440,μ = 2.784 mm-1,the final R = 0.0260 and wR = 0.0596 for 2684 observed reflections with I > 2σ(I).All the carbon atoms in the molecule are nearly coplanar except C(15),with a large conjugated system among the carbonyl group,pyrazole ring and the benzene ring.Three non-classical intermolecular hydrogen bonds help to stabilize the crystal lattice.The regioselectivity was rationalized based on the coordination of potassium ion with the N-anion and the carbonyl oxygen atom.     

Molecular basis for enantioselectivity of lipase from Chromobacterium viscosum toward the diesters of 2,3-dihydro-3-(4'-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol

2,3-Dihydro-3-(4'-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol, 1, is a chiral bisphenol useful for preparation of polymers. Previous screening of commercial hydrolases identified lipase from Chromobacterium viscosum (CVL) as a highly regio- and enantioselective catalyst for hydrolysis of diesters of 1. The regioselectivity was > or =30:1 favoring the ester at the 5-position, while the enantioselectivity varied with acyl chain length, showing the highest enantioselectivity (E = 48 +/- 20 S) for the dibutanoate ester. In this paper, we use a combination of nonsymmetrical diesters and computer modeling to identify that the remote ester group controls the enantioselectivity. First, we prepared nonsymmetrical diesters of (+/-)-1 using another regioselective, but nonenantioselective, reaction. Lipase from Candida rugosa (CRL) showed the opposite regioselectivity (>30:1), allowing removal of the ester at the 4'-position (the remote ester in the CVL-catalyzed reaction). Regioselective hydrolysis of (+/-)-1-dibutanoate (150 g) gave (+/-)-1-5-dibutanoate (89 g, 71% yield). Acylation gave nonsymmetrical diesters that varied at the 4'-position. With no ester at the 4'-position, CVL showed no enantioselectivity, while hindered esters (3,3-dimethylbutanoate) reacted 20 times more slowly, but retained enantioselectivity (E = 22). These results indicate that the remote ester group can control the enantioselectivity. Computer modeling confirmed these results and provided molecular details. A model of a phosphonate transition state analogue fit easily in the active site of the open conformation of CVL. A large hydrophobic pocket tilts to one side above the catalytic machinery. The tilt permits the remote ester at the 4'-position of only the (S)-enantiomer to bind in this pocket. The butanoate ester fits and fills this pocket and shows high enantioselectivity. Both smaller and larger ester groups show low enantioselectivity because small ester groups cannot fill this pocket, while longer ester groups extend beyond the pocket. An improved large-scale resolution of 1-dibutanoate with CVL gave (R)-(+)-1-dibutanoate (269 g, 47% yield, 92% ee) and (S)-(-)-1-4'-monobutanoate (245 g, 52% yield, 89% ee). Methanolysis yielded (R)-(+)-1 (169 g, 40% overall yield, >97% ee) and (S)-(-)-1 (122 g, 36% overall yield, >96% ee).     

Trialkylsilyl group-directed regioselective transformations of 2-(alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3-dithianes to alkynylcyclopropanes and enynes

[reaction: see text] The Cp(2)Ti[P(OEt)(3)](2)-promoted reaction of 2-(alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3-dithianes with 1-alkenes regioselectively produced [(trialkylsilyl)ethynyl]cyclopropanes with a formal allylic rearrangement. The reaction of the thioacetals with ketones proceeded with the same regioselectivity to produce 1-(trialkylsilyl)alk-3-en-1-ynes predominantly. It is suggested that these reactions proceed via the formation of titanium alpha-(silylethynyl)carbene complexes Cp(2)Ti=C(R)CCSi in preference to their regioisomers, alpha-silylalkynylcarbene complexes Cp(2)Ti=C(Si)CCR.     

1-(5-苄基四唑-2-乙酰基)-4-芳酰胺基硫脲及其环化产物的合成

据报道,酰胺基硫脲及其相应环化产物具有广泛的生理活性。如可消炎止痛,镇静,降血压,抗细菌和调节植物生长等。我们曾经通过α-苯基氰乙酰肼与芳酰基异硫氰酸酯缩合制备出一些新的酰胺基硫脲和相应的杂环衍生物,观察到它们在很低浓度下具有调节小麦芽鞘生长的活性。以前的一些研究结果得知,许多5-芳基四唑-2-烷基酸和它们的酰     

First syntheses of 2,2-dimethyl-7-(2'-methylbut-3'-en-2'-yl)-2H-chromen-6-ol and 2-(3'-methylbut-2'-enyl)-5-(2'-methylbut-3'-en-2'-yl)-1,4-benzoquinone, novel prenylated quinone derivatives from the New Zealand brown alga Perithalia capillaris

The first syntheses of 2,2-dimethyl-7-(2'-methylbut-3'-en-2'-yl)-2H-chromen-6-ol (1) and 2-(3'-methylbut-2'-enyl)-5-(2'-methylbut-3'-en-2'-yl)-1,4-benzoquinone (2), novel prenylated quinone derivatives from the New Zealand brown alga Perithalia capillaris, are reported, in which the key steps are consecutive Claisen rearrangements that proceed with both high chemo- and regioselectivity.     

Cycloisomerization of γ- and δ-acetylenic acids catalyzed by gold(I) chloride

We have developed a gold(I)-catalyzed intramolecular cyclization of γ- and δ-alkyne acids in mild conditions yielding various alkylidene lactones. Whereas a slight electronic effect of the R group was observed on the regioselectivity, bulky substituents on the R group bearing the alkyne strongly modify the reactivity. The cycloisomerization of o-alkynylbenzoic methyl esters was achieved rather with AuCl₃ as catalyst owing the presence of water affording exclusively the isocoumarins.     

Stereochemistry of Delta4 dehydrogenation catalyzed by an ivy (Hedera helix) Delta9 desaturase homolog

The stereochemistry of palmitoyl-ACP Delta(4) desaturase-mediated dehydrogenation has been examined by tracking the fate of deuterium atoms located on stereospecifically monodeuterated substrates-(4S)- and (4R)-[4-(2)H(1)]-palmitoyl-ACP and (5S)- and (5R)-[5-(2)H(1)]-palmitoyl-ACP. It was found that the introduction of the (Z)-double bond between C-4 and C-5 of a palmitoyl substrate occurs with pro-R enantioselectivity-a result which matches that obtained for a closely related homolog-castor stearoyl-ACP Delta(9) desaturase. These data show that despite the difference in regioselectivity between the two enzymes, the stereochemistry of hydrogen removal is conserved.     

Organocatalyzed regioselective and enantioselective synthesis of 1,4- and 1,2-dihydropyridines

Abstract

Herein, we introduce one of the first examples of asymmetric organocatalyzed synthesis of 1,2-dihydropyridines, affording enantioselective access to and partially solving regioselectivity challenges in the synthesis of dihydropyridines. We demonstrate that through modification of organocatalysts both 1,2- and 1,4-dihydropyridines (1,2- and 1,4-DHPs) can be obtained with high regioselectivity (ratio of 1,2-DHP/1,4-DHP from 95/5 to 0/100) and enantioselectivity (33% ee for 1,2-DHPs and up to 98% ee for 1,4-DHPs) in good yields (up to 87%).     

The complete characterization of a rhodium Lewis acid-dipolarophile complex as an intermediate for the enantioselective catalytic 1,3-dipolar cycloaddition of C,N-diphenylnitrone to methacrolein

The 1,3-dipolar cycloaddition reaction of C,N-diphenylnitrone with methacrolein is efficiently catalyzed by the rhodium diphosphine compound (SRh,RC)-[(eta5-C5Me5)Rh(R-Prophos)(H2O)](SbF6)2 [R-Prophos = (R)-(+)-1,2-bis(diphenylphosphino)-propane, 1.SbF6]; the asymmetric catalytic process occurs with reversal of regioselectivity, perfect endo selectivity, and up to 92% ee. The complete (NMR and X-ray analysis) characterization of the involved intermediate (SRh,RC)-[(eta5-C5Me5)Rh(R-Prophos)(methacrolein)](SbF6)2 (7.SbF6) allows us to interpret the observed selectivity.     

Calculated effect of substitutions on the regioselectivity of cyclization of alpha-sulfenyl-, alpha-sulfinyl-, and alpha-sulfonyl-(5R)-5-hexenyl radicals

Calculations of the activation energy of cyclization of alpha-sulfenyl-, alpha-sulfinyl-, and alpha-sulfonyl-5-hexenyl radicals and their respective 5-methyl-5-hexenyl counterparts at the G3MP2B3 level agree quite well with experimental data. The alpha-sulfinyl-5-hexenyl radical exhibits unexpected regioselectivity (93.99:6.01) via the 5-exo mode, whereas the alpha-sulfenyl- and alpha-sulfonyl-5-hexenyl radicals show increasing branching ratios of the 6-endo product. In contrast, the cyclization of the alpha-sulfur-based 5-methyl-substituted counterparts yields essentially the 6-endo products in all cases; in particular, the alpha-SO2-5-CH3-5-hexenyl radical gives high regioselectivity (98.85:1.15) via the 6-endo mode. Several other 5-substituted moieties, including the electron-withdrawing (CN and NO2) or electron-donating substituents (NH2), also proceed preferentially to 6-endo closure. The alpha-sulfonyl-5-amine-5-hexenyl radical is calculated to proceed to exclusively the 6-endo product, a demonstration of the high synthetic value of this reactant.     

Elucidating the Mechanism and Chemoselectivity in the PBu3-Catalyzed Rauhut-Currier Reaction of Chalcone with Ethyl Acrylate

Disclosing the chemoselectivity and regioselectivity of phosphine-catalyzed Rauhut-Currier (R−C) reaction remains a challenge. Here, a comprehensive study on the possible mechanisms and origins of the chemoselectivity and regioselectivity of PBu₃-catalyzed R−C reactions between ethyl acrylate and chalcone is performed by DFT. Both cross and homo R−C reactions are investigated and compared. The computational results show that the cross R−C reaction is energetically favorable than the homo R−C reaction, with head-to-tail product being generated preferentially. Moreover, the C−C bond formation process is identified to be the regioselectivity- and chemoselectivity-determining step. The CDFT and Parr function analyses are successfully used to predict the origins of chemoselectivity and regioselectivity, respectively. This work would provide a valuable case for exploring the origins of the chemoselectivity and regioselectivity of the phosphine catalyzed reactions, which should be helpful to understand and control the selectivities by rational design.     

Total regioselective and diastereospecific iodolysis of 2,3-epoxyamides promoted by SmI2: synthesis of (2R*,3R*)- or (2R,3S)-2-hydroxy-3-iodoamides

The use of samarium diiodide as a source of iodides is reported. Thus, 2-hydroxy-3-iodoamides were obtained, with total regioselectivity, by treatment of 2,3-epoxyamides, in which the oxirane ring is 2,3-disubstituted or 2,2,3-trisubstituted, with SmI2. The ring-opening reaction was diastereospecific and (2R*,3R*)- or (2R*,3S*)-2-hydroxy-3-iodoamides were obtained from cis- or trans-epoxyamides, respectively. The relative configuration of 2-hydroxy-3-iodoamides was established by X-ray analysis. A mechanism to explain this transformation has been proposed. The starting compounds 1 are easily prepared by the reaction of enolates derived from 2-chloroamides with aldehydes at -78 degrees C.     

Regioselective addition of nucleophiles to 1-(phenoxycarbonyl)-3-trialkylstannylpyridinium salts

The regioselectivity of nucleophilic addition to 1-(phenoxycarbonyl)-3-trialkylstannylpyridinium salts was studied.     

Cobalt catalysts for the alternating copolymerization of propylene oxide and carbon dioxide: combining high activity and selectivity

Synthetic pathways to (salcy)CoX (salcy = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminocyclohexane; X = halide or carboxylate) complexes are described. Complexes (R,R)-(salcy)CoCl, (R,R)-(salcy)CoBr, (R,R)-(salcy)CoOAc, and (R,R)-(salcy)CoOBzF(5) (OBzF(5) = pentafluorobenzoate) are highly active catalysts for the living, alternating copolymerization of propylene oxide (PO) and CO(2), yielding poly(propylene carbonate) (PPC) with no detectable byproducts. The PPC generated using these catalyst systems is highly regioregular and has up to 99% carbonate linkages with a narrow molecular weight distribution (MWD). Inclusion of the cocatalysts [PPN]Cl or [PPN][OBzF(5)] ([PPN] = bis(triphenylphosphine)iminium) with complex (R,R)-(salcy)CoCl, (R,R)-(salcy)CoBr, or (R,R)-(salcy)CoOBzF(5) results in remarkable activity enhancement of the copolymerization as well as improved stereoselectivity and regioselectivity with maximized reactivity at low CO(2) pressures. In the case of [PPN]Cl with (R,R)-(salcy)CoOBzF(5), an unprecedented catalytic activity of 620 turnovers per hour is achieved for the copolymerization of rac-PO and CO(2), yielding iso-enriched PPC with 94% head-to-tail connectivity. The stereochemistry of the monomer and catalyst used in the copolymerization has dramatic effects on catalytic activity and the PPC microstructure. Using catalyst (R,R)-(salcy)CoBr with (S)-PO/CO(2) generates highly regioregular PPC, whereas using (R)-PO/CO(2) with the same catalyst gives an almost completely regiorandom copolymer. The rac-PO/CO(2) copolymerization with catalyst rac-(salcy)CoBr yields syndio-enriched PPC, an unreported PPC microstructure. In addition, (R,R)-(salcy)CoOBzF(5)/[PPN]Cl copolymerizes (S)-PO and CO(2) with a turnover frequency of 1100 h(-1), an activity surpassing that observed in any previously reported system.     

Synthesis of enantiopure (alphaS,betaS)- or (alphaR,betaS)-beta-amino alcohols by complete regioselective opening of aminoepoxides by organolithium reagents LiAlH4 or LiAlD4

The reaction of chiral (2R,1'S)- or (2S,1'S)-2-(1-aminoalkyl)epoxides, 1 or 2 with a variety of organolithium compounds to obtain the corresponding (alphaS,betaS)- or (alphaR,betaS)- beta-amino alcohols in enantiopure form is reported. In both cases, the opening of the oxirane ring at C-3 proceeded with total regioselectivity. Moreover, the ring opening of aminoepoxides 1 or 2 by hydride (utilizing LiAlH4) to obtain the corresponding (2S,3S)- or (2R,3S)-3-aminoalkan-2-ols is also described. The reaction of 1 or 2 with LiAlD4 in place of LiAlH4 gave the corresponding (2S,3S)- or (2R,3S)-3-amino-1-deuterioalkan-2-ols.     

Regiochemical Control and Suppression of Double Bond Isomerization in the Heck Arylation of 1-(Methoxycarbonyl)-2,5-dihydropyrrole

Arylation of 1-(methoxycarbonyl)-2,5-dihydropyrrole under standard Heck reaction conditions produces a mixture of compounds. The olefin undergoes two types of palladium-catalyzed reactions: (a) arylation to provide C-3 arylated derivatives and (b) competing double bond isomerization. Addition of silver carbonate and thallium acetate fully suppressed the isomerization, and good yields of C-3 substituted compounds were achieved after arylation with aryl halides. With regard to aryl triflates as arylating agents, addition of lithium chloride was necessary to promote the Heck reaction. This additive excluded the use of silver and thallium salts, but high regioselectivity and good yields could be obtained by employing tri-2-furylphosphine as ligand. Arylation was rendered both regioselective and enantioselective (58% ee) with 1-naphthyl triflate as substrate utilizing a (R)-BINAP/thallium acetate combination. The C-3 arylated enamides were converted further into the corresponding 3-arylpyrrolidines.     

Absolute configuration and conformational stability of (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane

Enantiopure (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane were prepared using literature procedures and investigated using vibrational circular dichroism (VCD). Experimental absorption and VCD spectra of (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane in CCl(4) solution in the 2000-900 cm(-)(1) region were compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using the B3LYP/6-311G(2d, 2p) basis set for different conformers of (2R,5R)-2,5-dimethylthiolane and (2R,5R)-2,5-dimethylsulfolane. This comparison indicates that (+)-2,5-dimethylthiolane is of the (2R,5R)-configuration and has two predominant conformations in CCl(4) solution. In addition, (-)-2,5-dimethylsulfolane is of (2R,5R)-configuration and has only one predominant conformation. The stereochemical assignment is in agreement with literature.