Ir-catalyzed allylic amination/ring-closing metathesis: a new route to enantioselective synthesis of cyclic beta-amino alcohol derivatives

Ir-catalyzed allylic aminations of (E)-4-benzyloxy-2-butenyl methyl carbonate with benzylamine using Feringa's (Sa,Sc,Sc)-phosphoramidite as a chiral ligand afforded linear-aminated achiral product N,O-dibenzyl-4-amino-2-buten-1-ol regioselectively (linear/branched = >99/1), whereas the (E)-5-benzyloxy-2-pentenyl methyl carbonate showed completely opposite regioselectivity (linear/branched = >1/99) and afforded the optically active (3R)-N,O-dibenzylated 3-amino-1-penten-5-ol with very high enantioselectivity (96% ee), which was used as a key intermediate for the effective synthesis of various cyclic beta-amino alcohol derivatives through ring-closing metathesis in high yields.     

Stereoselective reactions of acyclic allylic phosphates with organocopper reagents

A series of acyclic allylic alcohols of general structure R(1)CH==CHCH(OH)R(2) were resolved by Sharpless kinetic resolution. The hydroxyl groups of these enantiomerically enriched alcohols were derivatized to diethyl phosphates, and the derivatives were reacted with organocopper reagents. Cleanest substitution reactions were observed with reagents R(3)(2)CuCNLi(2). With R(1) = Me and R(3) = n-Bu, the size of R(2) affected both the regioselectivity and stereoselectivity of the displacement. Larger R(2) groups gave higher regio- and stereoselectivities: with R(2) = 3-pentyl, >98% S(N)2' regioselectivity and >98% anti stereoselectivity were observed. Bn(2)CuCNLi(2) gave stereoselectivities comparable to those observed with n-Bu(2)CuCNLi(2) but t-Bu(2)CuCNLi(2) exhibited much lower diastereofacial preference.     

Diastereoselective Ni-catalyzed Negishi cross-coupling approach to saturated, fully oxygenated C-alkyl and C-aryl glycosides

A Ni-catalyzed Negishi cross-coupling approach to C-glycosides is described with an emphasis on C-aryl glycosides. The combination of NiCl2/PyBox in N,N'-dimethylimidazolidinone (DMI) enabled the synthesis of C-alkyl glycosides under mild reaction conditions. Moderate yields and beta-selectivities were obtained for C-glucosides, and good yields and high alpha-selectivities were the norm for C-mannosides. For C-aryl glycosides, reactions employing Ni(COD)2/(t)Bu-Terpy in N,N-dimethylformamide (DMF) were typically high yielding and provided C-glucosides with high beta-selectivities (1:>10 alpha:beta) and C-mannosides in moderate alpha-selectivities (3:1 alpha:beta); alpha-C-aryl glycosides could be obtained by the combination of Ni(COD)2/PyBox in DMF (>20:1 alpha:beta). The collective studies suggest that stereochemical control of the C-glycosides is dependent on the substrate and catalysts combination. The Negishi protocol displays excellent functional group tolerance, as demonstrated by its use in the first total synthesis of the natural product salmochelin SX.     

Fluorinated alcohol mediated displacement of the C10 acetoxy group of benzo[a]pyrene-7,8,9,10-tetrahydrotetraol tetraacetates: a new route to diol epoxide-deoxyguanosine adducts

We describe a novel trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP) mediated substitution reaction of the bay-region C10 acetoxy group in four stereoisomeric 7,8,9,10-tetraacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (tetraol tetraacetates, two pairs of cis and trans isomers at the 9,10 positions) by the exocyclic N2-amino group of O6-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine (3). The tetraacetates are derived from cis and trans hydrolysis of (+/-)-7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-1) and of (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-2) at C-10 followed by acetylation. Excellent yields and high regioselectivity were observed. Similar cis/trans product ratios were observed for each set of cis and trans tetraol tetraacetates derived from DE-1 ( approximately 75/25) and from DE-2 (approximately 67/33) in HFP. This strongly suggests that the substitution proceeds via an SN1 mechanism involving a carbocation intermediate that is common to the cis and trans tetraacetates. Since it is likely that the cis and trans products from 3 arise from different conformations of the carbocation, its lifetime must be sufficiently long to permit conformational equilibration before its capture by the purine nucleophile. The corresponding reaction of (+/-)-9alpha-bromo-7beta,8alpha,10beta-triacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrene with 3 in HFP was highly regio- and stereoselective and gave exclusively trans 10beta-adducts. This newly developed substitution reaction provides an attractive alternative synthetic strategy for the preparation of polycyclic hydrocarbon adducted oligonucleotide building blocks.     

Synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a class of potent nicotinic acetylcholine receptor-ligands

In an attempt to generate nicotinic acetylcholine receptor (nAChR) ligands selective for the alpha4beta2 and alpha7 subtype receptors we designed and synthesized constrained versions of anabasine, a naturally occurring nAChR ligand. 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, and several of their derivatives have been synthesized in both an enantioselective and a racemic manner utilizing the same basic synthetic approach. For the racemic synthesis, alkylation of N-(diphenylmethylene)-1-(pyridin-3-yl)methanamine with the appropriate bromoalkyltetrahydropyran gave intermediates which were readily elaborated into 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane and 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via a ring opening/aminocyclization sequence. An alternate synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via the alkylation of N-(1-(pyridin-3-ylethylidene)propan-2-amine has also been achieved. The enantioselective syntheses followed the same general scheme, but utilized imines derived from (+)- and (-)-2-hydroxy-3-pinanone. Chiral HPLC shows that the desired compounds were synthesized in >99.5% ee. X-ray crystallography was subsequently used to unambiguously characterize these stereochemically pure nAChR ligands. All compounds synthesized exhibited high affinity for the alpha4beta2 nAChR subtype ( K i < or = 0.5-15 nM), a subset bound with high affinity for the alpha7 receptor subtype ( K i < or = 110 nM), selectivity over the alpha3beta4 (ganglion) receptor subtype was seen within the 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane series and for the muscle (alpha1betagammadelta) subtype in the 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane series.     

Efficient and beta-Stereoselective Synthesis of 4(5)-(beta-D-Ribofuranosyl)- and 4(5)-(2-Deoxyribofuranosyl)imidazoles(1)

A synthetic route to 4(5)-(beta-D-ribofuranosyl)imidazole (1), starting from 2,3,5-tri-O-benzyl-D-ribose (5), was developed via a Mitsunobu cyclization. Reaction of 5 with the lithium salt of bis-protected imidazole afforded the corresponding 5-ribosylimidazole 7RS. Hydrolysis of 7RS gave a 1:1 mixture of diol isomers 8R and 8S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8RS using N,N,N',N'-tetramethylazodicarboxamide and Bu(3)P exclusively afforded benzylated beta-ribofuranosyl imidazole 9beta in 92% yield, accompanied by alpha-anomer 9alpha, in a ratio of 26.3:1. The configuration of 9beta was established by X-ray crystallography of ethoxycarbonyl derivative 10beta. Reductive debenzylation of 9beta over Pd/C was carried out, and the synthesis of 1 was attained from starting 5 in four steps and 87% overall yield. This synthetic methodology was extended to the synthesis of 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole (2). Mitsunobu cyclization of a 1:1 mixture of the corresponding diol isomers 14RS produced 15beta and 15alpha in a ratio of 5.4:1. The synthesis of 2 was attained in a 59% overall yield from the starting 3,5-di-O-benzyl-2-deoxy-D-ribose (12). beta-Stereoselective glycosylation in the key step is discussed and explained by intramolecular hydrogen bonding between an NH in the imidazole and the oxygen functional group in the sugar moiety.     

Controlling substitution chemistry in ruthenium(II) systems. Synthesis of heteroleptic complexes incorporating the [Ru([9]aneS3)]2+ metal center

The complex [Ru(py)3([9]aneS3)][PF6]2, 1 (py = pyridine), has proved to be a suitable starting material for the synthesis of heteroleptic Ru(II) complexes. By exploiting unfavorable steric interactions between 2-H and 6-H hydrogens of coordinated pyridyl ligands, we have synthesized half-sandwich complexes incorporating the thiocrown [9]aneS3 and a variety of facially coordinated N-donor ligands. Such complexes are easily prepared: Stirring 1 at room temperature in the presence of a suitable nitrile ligand leads to the exclusive substitution of one py ligand to produce complexes such as [([9]aneS3)Ru(py)2(NCMe)][PF6]2, 2. However, if the same reaction is carried out at higher temperatures, two py ligands are substituted, leading to complexes such as [([9]aneS3)Ru(py)(NCMe)2][PF6]2, 3. An alternative approach to such heteroleptic species has also been developed which exploits the restricted ability of thioethers to neutralize positive charges through sigma-donation. This phenomenon allows the synthesis of heteroleptic complexes in a two-step procedure via monocationic species. By variation of the donor/acceptor properties of ligands incorporated into the [Ru([9]aneS3)]2+ metal center, it is possible to tune the Ru(III)/Ru(II) redox couple over a range of > 700 mV. The solid-state structures of 1-3 were confirmed by X-ray crystallography studies. Crystal data: C22H30F12N4O2P2RuS3 (1.CH3NO2), monoclinic, Cc, a = 23.267(5) A, b = 11.5457(18) A, c = 26.192(5) A, alpha = 90 degrees, beta = 114.836(10) degrees, gamma = 90 degrees, Z = 8; C18H25F12N3P2RuS3 (2), triclinic, P1, a = 11.3958(19) A, b = 11.4280(19) A, c = 11.930(2) A, alpha = 100.518(3) degrees, beta = 100.542(3) degrees, gamma = 112,493(3) degrees, Z = 2; C15H23F12N3P2RuS3 (3), orthorhombic, Pna2(1)), a = 14.748(5) A, b = 18.037(18) A, c = 10.341(5) A, alpha = 90 degrees, beta = 90 degrees, gamma = 90 degrees, Z = 4.     

Synthesis, characterization, and substitution chemistry of [Bu4N]2[W6Cl8(OSO2CF3)6]. A versatile precursor for axially substituted clusters containing the (W6Cl8)4+ core

The new cluster [Bu4N]2[W6Cl8(OSO2CF3)6] (1) has been prepared and structurally characterized. This material is an effective precursor for the generation of cluster ions with the general formula [W6C18L6]n (L = Cl-, Br-, I-, NCS-, NCO-, NCSe-, and O=PPh3; n = 2- or 4+). The last three clusters are new. The products have been characterized by IR spectroscopy, NMR spectroscopy, and FAB mass spectrometry. In addition to 1, the products [Bu4N]2[W6C18(NCS)6] (5) and [Bu4N]2[W6C18(NCO)6] (7) were structurally characterized. Crystal data for 1: space group, P2(1/c) (No. 14); a = 11.116(5) A; b = 27.952(1) A; c = 24.516(1) A; beta = 95.182(9) degrees; V = 7586.3(5) A3; Z = 4. Crystal data for 5: space group, P2(1/n) (No. 14); a = 11.3323(9) A; b = 12.3404(9) A; c = 44.583(3) A; beta = 97.089(1) degrees ; V = 6187.1(7) A3; Z = 4. Crystal data for 7: space group, P1 (No. 2); a = 11.8009(8) A; b = 11.9332(8) A; c = 11.9522(8) A; alpha = 77.904(1) degrees; beta = 95.182(9) degrees; gamma = 62.574(1) degrees V = 1450.5(2) A3; Z = 1.     

Highly stereoselective radical carbonylations of gem-dihalocyclopropane derivatives with CO

A couple of radical carbonylations of gem-dihalocyclopropanes 1 using CO and Bu3SnH (formylation) or Bu3Sn(CH2CH=CH2) (allylacylation) successfully proceeded to give trans and cis adducts (2 and 3) with good to excellent stereoselectivity (trans/cis = >99/1-75/25 or 17/83-1/99). The formylation of 2,3-cis-disubstituted 1,1-dihalocyclopropanes enhanced trans selectivity (trans/cis = >99/1-95/5), whereas both 2,3-cis-disubstituted and 2-monosubstituted 1,1-dihalocyclopropanes underwent allylacylation with nearly complete trans selectivity (trans/cis = >99/1). Inherently less reactive gem-dichloro- and bromochlorocyclopropanes than gem-dibromocyclopropanes served as favorable substrates. [reaction: see text].     

Solid-phase synthesis of alpha-Gal epitopes: on-resin analysis of solid-phase oligosaccharide synthesis with 19F NMR spectroscopy

A route for solid-phase synthesis of the alpha-Gal epitopes Gal(alpha1-3)Gal(beta1-4)Glc and Gal(alpha1-3)Gal(beta1-4)GlcNAc is described. These trisaccharide antigens are responsible for hyperacute rejection in xenotransplantation of porcine organs. Optimization of the solid-phase synthesis relied on use of fluorinated protective groups for the carbohydrate building blocks and use of a fluorinated linker. This allowed convenient on-resin analysis of the reactions with gel-phase (19)F NMR spectroscopy. Conditions were established which allowed reductive ring-opening of 4,6-O-benzylidene acetals to be performed on the solid phase with high regioselectivity to furnish the corresponding 6-O-benzyl ethers. It was found that glycosylations could be conveniently carried out by using thioglycosides as donors with N-iodosuccinimide and trifluoromethanesulfonic acid as the promoter system. With use of these conditions a challenging alpha-glycosidic linkage was successfully installed with complete stereoselectivity in the final glycosylation. It was also established that fluorinated benzoates, benzyl ethers, and benzylidene acetals display almost identical chemical properties as their nonfluorinated counterparts, a finding that is essential for future use of fluorinated protective groups in solid-phase oligosaccharide synthesis.     

Improved scalable syntheses of mono- and bis-urethane derivatives of ornithine

In the search for a practical route to ornithine bisurethane derivatives useful for peptide synthesis, we elaborated the simple and efficient (86% yield) synthesis of N(epsilon)-tert-butoxycarbonyl-L-ornithine copper(II) complex (1). This served as substrate for obtaining N(epsilon)-tert-butoxycarbonyl-L-ornithine (2), N(alpha)-benzyloxycarbonyl-N(epsilon)-tert-butoxycarbonyl-L-ornithine (3) and N(alpha)-(9-fluorenyl)methoxycarbonyl-N(epsilon)-tert-butoxycarbonyl-L-ornithine (4). These were synthesized in 94-95% yields and with a purity above 99%.     

New framework connectivity patterns in templated networks: the creatinine zinc phosphites C4N3OH7.ZnHPO3, C4N3OH7.Zn(H2O)HPO3, and (C4N3OH7)2.ZnHPO3.H2O

The syntheses, crystal structures, and properties of C(4)N(3)OH(7).ZnHPO(3), C(4)N(3)OH(7).Zn(H(2)O)HPO(3), and (C(4)N(3)OH(7))(2).ZnHPO(3).H(2)O are reported. These new creatinine zinc phosphites are built up from networks of vertex-sharing HPO(3) pseudopyramids and various types of ZnO(2)N(2), ZnO(3)N, and ZnO(2)N(H(2)O) tetrahedra, resulting in extended structures of different dimensionalities (as sheets, clusters, and chains, respectively). They demonstrate the structural effect of incorporating "terminal" (nonnetworking) Zn-N and Zn-OH(2) moieties into zinc centers. Crystal data: C(4)N(3)OH(7).ZnHPO(3), triclinic, P1 (No. 2), a = 8.9351(4) A, b = 9.5011(4) A, c = 9.9806(4) A, alpha = 87.451(1) degrees, beta = 85.686(1) degrees, gamma = 89.551(1) degrees, Z = 4; C(4)N(3)OH(7).Zn(H(2)O)HPO(3), monoclinic, P2(1)/c (No. 14), a = 10.1198(7) A, b = 7.2996(5) A, c = 13.7421(9) A, beta = 107.522(1) degrees, Z = 4; (C(4)N(3)OH(7))(2).ZnHPO(3).H(2)O, triclinic, P1 (No. 2), a = 10.7289(6) A, b = 10.9051(6)A, c = 13.9881(8) A, alpha = 89.508(1) degrees, beta = 74.995(1) degrees, gamma = 74.932(1) degrees, Z = 4.     

Imide Transfer Properties and Reactions of the Magnesium Imide ((THF)MgNPh)(6): A Versatile Synthetic Reagent

Imide transfer properties of ((THF)MgNPh)(6) (1) and the synthesis of the related species {(THF)MgN(1-naphthyl)}(6).2.25THF (2), via the reaction of dibutylmagnesium with H(2)N(1-naphthyl), in a THF/heptane mixture are described. Treatment of 1 with Ph(2)CO, 4-Me(2)NC(6)H(4)NO, t-BuNBr(2) (3), PCl(3), or MesPCl(2) (Mes = 2,4,6-Me(3)C(6)H(2)-) leads to the isolation of Ph(2)CNPh (4), 4-Me(2)NC(6)H(4)NNPh (5), t-BuNNPh (6), (PhNPCl)(2) (7), or (MesPNPh)(2) (8) in moderate yield. Reaction between 1 and GeCl(2).dioxane, SnCl(2), or PbCl(2) affords the M(4)N(4) (M = Ge, Sn, Pb) cubane imide derivative (GeNPh)(4) (9), [(SnNPh)(4).{MgCl(2)(THF)(4)}](infinity) (10), (SnNPh)(4).0.5PhMe (11), or (PbNPh)(4).0.5PhMe (12). Interaction of 1 with Ph(3)PO, (Me(2)N)(3)PO, or Ph(2)SO furnishes the complex (Ph(3)POMgNPh)(6) (13), {(Me(2)N)(3)POMgNPh}(6).2PhMe (14), or (Ph(2)SOMgNPh)(6) (15). The addition of 3 equiv of MgBr(2) to 1 gives 1.5 equiv of ((THF)Mg)(6)(NPh)(4)Br(4) (16) in quantitative yield, whereas treatment of 16 with 4 equiv of 1,4-dioxane is an alternative synthetic route to 1. Compounds 2, 3, 9, 10, and 14 were characterized by X-ray crystallography. The reactions demonstrate that 1 is a versatile and useful reagent for the synthesis of a variety of main group imides. Crystal data at 130 K with Mo Kalpha (lambda = 0.710 73 ?) radiation for 3 or Cu Kalpha (lambda = 1.541 78 ?) radiation for 2, 9, 10, and 14: 2, C(93)H(108)Mg(6)N(6)O(7.25), a = 28.101(7) ?, b = 35.851(7) ?, c = 36.816(7) ?, Z = 2, space group Fddd, R = 0.068 for 3500 (I > 2sigma(I)) data; 3, C(4)H(9)Br(2)N, a = 6.682(2) ?, b = 10.834(3) ?, c = 11.080(3) ?, alpha = 66.25(2) degrees, beta = 89.88(2) degrees, gamma = 82.53(2) degrees, Z = 4, space group P&onemacr;, R = 0.038 for 2043 (I > 2sigma(I)) data; 9, C(24)H(20)Ge(4)N(4), a = 10.749(2) ?, b = 12.358(3) ?, c = 35.818(7) ?, Z = 8, space group Pbca, R = 0.040 for 2981 (I > 2sigma(I)) data; 10, C(40)H(52)Cl(2)MgN(4)O(4)Sn(4), a = 12.770(3) ?, b = 13.554(3) ?, c = 25.839(5) ?, Z = 4, space group P2(1)2(1)2(1), R = 0.040 for (I > 2sigma(I)) data; 14, C(86)H(154)Mg(6)N(4)O(6)P(6), a = 22.478(4) ?, b = 16.339(3) ?, c = 29.387(6) ?, Z = 4, space group Pbcn, R = 0.081 for 4696 (I >2sigma(I)) data.     

Strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays based on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides: application to natural product synthesis

We describe a new strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays. This strategy relies on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides promoted by the Sm-BINOL-Ph(3)As[double bond]O (1:1:1) complex, followed by a conversion of morpholinyl amides into ketones and diastereoselective ketone reduction. Highly enantio- (up to >99 % ee) or diastereoselective (up to >99.5:0.5) epoxidation was achieved using 5-10 mol % of the Sm complex to afford synthetically very useful, nearly optically pure alpha,beta-epoxy morpholinyl amides. Stereoselectivity of the epoxidation was controlled by the chirality of BINOL with overwhelming inherent diastereofacial preference for the substrate. Combination with the syn- and anti-selective ketone reduction with the highly catalyst-controlled epoxidation allowed for an iterative strategy for the syntheses of all possible stereoisomers of 1,3-polyol arrays. Eight possible stereoisomers of 1,3,5,7-tetraol arrays were synthesized with high to excellent stereoselectivity. Moreover, the efficiency of the present strategy was successfully demonstrated by enantioselective syntheses of several 1,3-polyol/alpha-pyrone natural products, for example, cryptocaryolone diacetate.     

Construction of highly glycosylated mucin-type glycopeptides based on microwave-assisted solid-phase syntheses and enzymatic modifications

A MUC1-related glycopeptide having five core-2 hexasaccharide branches (C330H527N46O207, MW = 8450.9) was synthesized by a new strategy using a combination of microwave-assisted solid-phase synthesis (MA-SPGS) and enzymatic sugar elongation. Synthesis of a key glycopeptide intermediate was best achieved in a combination of PEGA [poly(ethylene glycol)-poly-(N,N-dimethylacrylamide) copolymer] resin and MA-SPGS using glycosylated amino acid building blocks with high speed and high purity. Deprotection of the glycopeptide intermediate and subsequent glycosyltransferase-catalyzed sugar elongations were performed for generation of the additional diversities with the sugar moieties of glycopeptides using beta1,4-galactosyltransferase (beta1,4-GalT) and two kinds of alpha2,3-sialyltransferases [ST3Gal III; alpha2,3-(N)-SiaT and ST3Gal II; alpha2,3-(O)-SiaT]. These reactions proceeded successfully in the presence of 0.2% Triton X-100 to convert the chemically synthesized trisaccharide glycans to disialylated hexasaccharide.     

Highly alpha- and beta-selective radical C-glycosylation reactions using a controlling anomeric effect based on the conformational restriction strategy. A study on the conformation-anomeric effect-stereoselectivity relationship in anomeric radical reactions.

We hypothesized that, because the stereoselectivity of anomeric radical reactions was significantly influenced by the anomeric effect, which can be controlled by restricting the conformation of the radical intermediate, the proper conformational restriction of the pyranose ring of the substrates would therefore make highly alpha- and beta-stereoselective anomeric radical reactions possible. Thus, the conformationally restricted 1-phenylseleno-D-xylose derivatives 9 and 10, restricted in a (4)C(1)-conformation, and 11 and 12, restricted in a (1)C(4)-conformation, were designed and synthesized by introducing the proper protecting groups on the hydroxyl groups on the pyranose ring as model substrates for the anomeric radical reactions. The radical deuterations with Bu(3)SnD and the C-glycosylation with Bu(3)SnCH(2)CH [double bond] CH(2) or CH(2) [double bond] CHCN, using the (4)C(1)-restricted substrates 9 and 10, afforded the corresponding alpha-products (alpha/beta = 97:3-85:15) highly stereoselectively, whereas the (1)C(4)-restricted substrates 11 and 12 selectively gave the beta-products (alpha/beta = 1:99-0:100). Thus, stereoselectivity was significantly increased by conformational restriction and was completely inverted by changing the substrate conformation from the (4)C(1)-form into the (1)C(4)-form. Ab initio calculations suggested that the radical intermediates produced from these substrates possessed the typical (4)C(1)- or (1)C(4)-conformation, which was similar to that of the substrates, and that the anomeric effect in these conformations would be the factor controlling the transition state of the reaction. Therefore, the highly alpha- and beta-selective reactions would occur because of the anomeric effect, which could be manipulated by conformational restriction of the substrates, as expected. This would be the first radical C-glycosylation reaction to provide both alpha- and beta-C-glycosides highly stereoselectively.     

Syntheses,structures, and properties of the bis(cyclopentadienyl) rare-earth imidodiphosphinochalocogenido compounds Cp2Ln[N(QPPh2)2] (Ln = La,Gd, Er,or Yb for Q = Se; Ln = Yb for Q = S)

The compounds Cp2Ln[N(QPPh2)2] (Ln = La (1), Gd (2), Er (3), or Yb (4) for Q = Se, Ln = Yb (5) for Q = S) have been synthesized from the corresponding rare-earth tris(cyclopentadienyl) compound and H[N(QPPh2)2]. The structures of compounds 1, 2, 3, and 5, as determined by X-ray crystallography, consist of a Cp2Ln fragment, coordinated eta 3 through two chalcogen atoms and an N atom of the imidodiphosphinochalcogenido ligand [N(QPPh2)2]-. In compound 4, the Cp2Yb moiety is coordinated eta 2 through the two Se atoms of the [N(SePPh2)2]-ligand. 31P and 77Se (for 1) NMR spectroscopies lend insight into the solution nature of these species. Crystal data: 1, C34H30LaNP2Se2, triclinic, P1, a = 9.7959(10) A, b = 12.4134(13) A, c = 13.9077(14) A, alpha = 88.106(2) degrees, beta = 88.327(2) degrees, gamma = 68.481(2) degrees, V = 1572.2(3) A3, T = 153 K, Z = 2, and R1(F) = 0.0257 for the 5947 reflections with I > .2 sigma(I); 2, C34H30GdNP2Se2, triclinic, P1, a = 9.7130(14) A, b = 12.2659(17) A, c = 13.953(2) A, alpha = 88.062(2) degrees, beta = 87.613(2) degrees, gamma = 69.041(2) degrees, V = 1550.7(4) A3, T = 153 K, Z = 2, and R1(F) = 0.0323 for the 5064 reflections with I > 2 sigma(I); 3, C34H30ErNP2Se2, triclinic, P1, a = 9.704(2) A, b = 12.222(3) A, c = 13.980(4) A, alpha = 88.230(4) degrees, beta = 87.487(4) degees, gamma = 69.107(4) degrees, V = 1547.4(7) A3, T = 153 K, Z = 2, and R1(F) = 0.0278 for the 6377 reflections with I > 2 sigma(I); 4, C34H30NP2Se2Yb.C4H8O, triclinic, P1, a = 12.087(4) A, b = 12.429(4) A, c = 23.990(7) A, alpha = 89.406(5) degrees, beta = 86.368(5) degrees, gamma = 81.664(5) degrees, V = 3558.8(18) A3, T = 153 K, Z = 4, and R1(F) = 0.0321 for the 11,883 reflections with I > 2 sigma(I); and 5, C34H30NP2S2Yb, monoclinic, P21/n, a = 13.8799(18) A, b = 12.6747(16) A, c = 17.180(2) A, beta = 91.102(3) degrees, V = 3021.8(7) A3, T = 153 K, Z = 4, and R1(F) = 0.0218 for the 6698 reflections with I > 2 sigma(I).     

Xanthene-bridged cofacial bisporphyrins

The synthesis and characterization of cofacial bisporphyrins juxtaposed by xanthene-bridged pillars are presented. The one-pot preparation of the xanthene dialdehyde avoids the lengthy bridge synthesis accompanying other cofacial porphyrin systems, thus allowing for the facile preparation of homobimetallic zinc (10), copper (11), and nickel (12) complexes. The cofacial orientation of the two porphyrin macrocycles was confirmed by X-ray crystallography. Structural data are provided for bisporphyrins 10-12: 10 (C79H82N8OZn2), triclinic, space group P1, a = 11.2671(2) A, b = 14.9809(2) A, c = 20.4852(2) A, alpha = 101.6680(10) degrees, beta = 100.8890(10) degrees, gamma = 101.8060(10) degrees, Z = 2; 11 (C79H82N8OCu2), triclinic, space group P1, a = 11.21410(10) A, b = 14.9539(5) A, c = 20.6915(7) A, alpha = 101.810(2) degrees, beta = 101.044(2) degrees, gamma = 101.722(2) degrees, Z = 2; 12 (C79H82N8ONi2), monoclinic, space group C2/c, a = 24.1671(4) A, b = 10.669 A, c = 50.5080(9) A, beta = 99.553(2) degrees, Z = 8. Exciton interactions between the porphyrin rings are apparent in electronic spectra, consistent with the cofacial superstructure. The combination of structural and spectroscopic data provides a basis for the design of additional metal derivatives for the activation of dioxygen and other small molecules.     

Highly enantioselective reduction of beta,beta-disubstituted aromatic nitroalkenes catalyzed by Clostridium sporogenes

This is the first report of the use of Clostridium sporogenes extracts for enantioselective reduction of CC double bonds of beta,beta-disubstituted (1) and alpha,beta-disubstituted nitroalkenes (3). Crude enzyme preparations reduced aryl derivatives 1a-e and 1h, in 35-86% yield with > or =97% ee. Reduction of (E)- and (Z)-isomers of 1c gave the same enantiomer of 2c (> or =99% ee). In contrast, alpha,beta-disubstituted nitroalkene 3a was a poor substrate, yielding (S)- 4a in low yield (10-20%), and the ee (30-70% ee) depended on NADH concentration. An efficient synthesis of a library of nitroalkenes 1 is described.     

Synthesis and characterization of diverse coordination polymers. Linear and zigzag chains involving their structural transformation via intermolecular hydrogen-bonded, interpenetrating ladders polycatenane, and noninterpenetrating square grid from long, rigid N,N'-bidentate ligands: 1,4-bis[(x-pyridyl)ethynyl]benzene (x = 3 and 4)

The long, rigid ligands 1,4-bis[(3-pyridyl)ethynyl]benzene (L1) and 1,4-bis[(4-pyridyl)ethynyl]benzene (L2) were used in the synthesis of 10 new organic-inorganic coordination frameworks, each of them adopting different structural motifs. Synthesis, single-crystal X-ray structure determination, and spectroscopic and thermogravimetric analyses are presented. The reactions between M(NO3)2 x xH2O; M = Cd(II), Cu(II), and Co(II); x = 3-6 and Cu(hfac)2 x H2O [hfac = bis(hexafluoroacetylacetonato)] with L1 afforded the following one-dimensional zigzag chain structures: [Cd(C20H12N2)0.5(NO3)(CH3OH)]n (1, monoclinic, C2/c; a = 7.586(1) A, b = 23.222(1) A, c = 13.572(1) A, beta = 92.824(1), Z = 4); [{Cu(C20H12N2)(NO3)2(CH3OH)} x CH3OH]n (2, orthorhombic, P2(1)2(1)2(1); a = 8.589(1) A, b = 15.766(1) A, c = 17.501(1) A, Z = 4); [Co(C20H12N2)2(NO3)2(H2O)2] (5, triclinic, P1; a = 7.493(1) A, b = 8.948(1) A, c = 14.854(1) A, alpha = 100.427(1), beta = 97.324(1), gamma = 110.901(1), Z = 1); [Cu(C20H12N2)(hfac)2]n (4, monoclinic, C2/c, a = 18.828(1) A, b = 14.671(1) A, c = 13.427(1) A, beta = 90.447(1) degrees, Z = 4). Moreover, the minority phase compound formed from Cu(NO3)2 x 3H2O and L1 yielded a metallocyclic chain structure, [Cu(C20H12N2)(NO3)]n (3, triclinic, P; a = 8.728(1) A, b = 10.018(1) A, c = 11.893(1) A, alpha = 109.991(1), beta = 97.109(1), gamma = 115.542(1), Z = 1). In addition to the dinuclear coordination complex 5, all other polymeric structures (1-4) from L1 are composed of interpenetrating 2D and 3D cross-linked zigzag chains via hydrogen-bonding interactions. The reactions between M(NO3)2 x xH2O; M = Cd(II), Cu(II), and Co(II); x = 3-6 and Cu(hfac)2 x H2O [hfac = bis(hexafluoroacetylacetonato)] and L2 were dependent on the nature of the metal center and resulted in the formation of four different interpenetrating and noninterpenetrating compounds (6-10): [Co(C20H12N2)1.5(NO3)2]n (6, triclinic, P; a = 14.172(1) A, b = 15.795(1) A, c = 18.072(1) A, alpha = 115.380(1), beta = 101.319(1), gamma = 93.427(2), Z = 4), which consists of T-shaped building blocks assembled into three-dimensional interpenetrating polycatenated ladders; [Cd(C20H12N2)2(NO3)2]n (7, monoclinic, I2/a; a = 11.371(1) A, b = 20.311(2) A, c = 15.240(2) A, beta = 100.201(2) degrees, Z = 4), which adopts a two-dimensional noninterpenetrating square-grid motif; [Cu(C20H12N2)(hfac)2]n (8, monoclinic, I2/a; a = 11.371(1) A, b = 20.311(2) A, c = 15.240(2) A, beta = 100.201(2) degrees, Z = 4), composed of three sets of distinct one-dimensional linear chains; [Cu(C20H12N2)(EtOH)(NO3)2] [Cu(C20H12N2)1.5(NO3)2] x 2EtOH (9, triclinic, P; a = 12.248(2) A, b = 13.711(3) A, c = 18.257(4) A, alpha = 108.078(4) degrees, beta = 97.890(4) degrees, gamma = 103.139(5) degrees, Z = 2) and [Cu(C20H12N2)(MeOH)(NO3)2] [Cu(C20H12N2)1.5(NO3)2] x 2MeOH (10, triclinic, P; a = 12.136(1) A, b = 13.738(2) A, c = 17.563(3) A, alpha = 107.663(3) degrees, beta = 94.805(4) degrees, gamma = 104.021(4) degrees, Z = 2). Both 9 and 10 stack into infinite interpenetrating ladders through bundles of infinite chains and are described in our preliminary communication.