One-Pot Chemo<i>-</i>, Regio<i>-</i>, and Stereoselective Double-Differential Glycosidation Mediated by Lanthanide Triflates

Nuanced activation of n-pentenyl, thioglycoside, and trichloroacetimidate donors by lanthanide salts coupled with donor/acceptor matching can simplify oligosaccharide assembly. Thus, a one-pot, double-differential glycosidation process can be designed, in which an n-pentenyl acceptor-diol is chemo- and regioselectively glycosidated by using an n-pentenyl ortho ester under the agency of Yb(OTf)3/NIS followed by in situ addition of a 2-O-acylated trichloroacetimidate or ethyl thioglycoside to effect stereoselective glycosidation at the remaining OH

One-Pot Chemo<i>-</i>, Regio<i>-</i>, and Stereoselective Double-Differential Glycosidation Mediated by Lanthanide Triflates

Nuanced activation of n-pentenyl, thioglycoside, and trichloroacetimidate donors by lanthanide salts coupled with donor/acceptor matching can simplify oligosaccharide assembly. Thus, a one-pot, double-differential glycosidation process can be designed, in which an n-pentenyl acceptor-diol is chemo- and regioselectively glycosidated by using an n-pentenyl ortho ester under the agency of Yb(OTf)3/NIS followed by in situ addition of a 2-O-acylated trichloroacetimidate or ethyl thioglycoside to effect stereoselective glycosidation at the remaining OH

Synthesis and Reactivity of the Octahedral d⁶ Parent Amido Complexes TpRu(L)(L‘)(NH₂) (Tp = Hydridotris(pyrazolyl)borate; L = L‘ = PMe₃, P(OMe)₃; L = CO, L‘ = PPh₃) and [TpRu(PPh₃)(NH₂)₂][Li]

A series of octahedral ruthenium(II) parent amido complexes of the type TpRu(L)(L‘)(NH2) (L/L‘ = neutral and two-electron-donor ligands) and [TpRu(PPh3)(NH2)2][Li] (Tp = hydridotris(pyrazolyl)borate) have been prepared. Preliminary reactivity studies indicate that the amido moieties are highly basic:  for example, TpRu(L)(L‘)(NH2) complexes deprotonate phenylacetylene at room temperature to form [TpRu(L)(L‘)(NH3)][PhC2] ion pairs, as determined by 1H NMR spectroscopy

Preparation of the Octahedral d⁶ Amido Complex TpRu(CO)(PPh₃)(NHPh) (Tp = Hydridotris(pyrazolyl)borate): Solid-State Structural Characterization and Reactivity

The reaction of TpRu(CO)(PPh3)(OTf) (2) with LiNHPh affords the amido complex TpRu(CO)(PPh3)(NHPh) (3) in 88% isolated yield. The amido complex 3 has been characterized by 1H NMR, 13C NMR, 31P NMR, elemental analysis, cyclic voltammetry, and a solid-state X-ray diffraction study. Variable temperature NMR studies have revealed a rotational barrier around the ruthenium−amido nitrogen bond of 3 of 12 kcal/mol (transformation of the major isomer to the minor isomer). The solid-state structure of 3 discloses a pyramidal amido moiety. Heating benzene solutions of the amido complex 3 and 1,4-cyclohexadiene or 9,10-dihydroanthracene results in no observable reaction. Reaction of complex 2 with excess aniline yields [TpRu(CO)(PPh3)(NH2Ph)][OTf] (4)

Synthesis of a Malaria Candidate Glycosylphosphatidylinositol (GPI) Structure: A Strategy for Fully Inositol Acylated and Phosphorylated GPIs

A congener of the glycosylphosphatidylinositol (GPI) membrane anchor present on the cell surface of the malaria pathogen Plasmodium falciparum has been synthesized. This GPI is an example of a small number of such membrane anchors that carry a fatty acyl group at O-2 of the inositol. Although the acyl group plays crucial roles in GPI biosynthesis, it rarely persits in mature molecules. Other notable examples are the mammalian GPIs CD52 and AchE. The presence of bulky functionalities at three contiguous positions of the inositol moiety creates a very crowded environment that poses difficulties for carrying out selective chemical manipulations. Thus installations of the axial long-chain acyl group and neighboring phosphoglyceryl complex were fraught with obstacles. The key solution to these obstacles in the successful synthesis of the malarial candidate and prototype structures involved stereoelectronically controlled opening of a cyclic ortho ester. The reaction proceeds in very good yields, the desired axial diastereomer being formed predominantly, even more so in the case of long-chain acyl derivatives. The myoinositol precursor was prepared from methyl α-d-glucopyranoside by the biomimetic procedure of Bender and Budhu. For the glycan array, advantage was taken of the fact that (a) n-pentenyl ortho ester donors are rapidly and chemospecifically activated upon treatment with ytterbium triflate and N-iodosuccinimide and (b) coupling to an acceptor affords α-coupled product exclusively. A strategy for obtaining the GPI's α-glucosaminide component from the corresponding α-mannoside employed Deshong's novel azide displacement procedure. Thus all units of the glycan array were obtained from a β-d-manno-n-pentenyl ortho ester, this being readily prepared from d-mannose in three easy, high-yielding steps. The “crowded environment” at positions 1 and 2, noted above, could conceivably be relieved by migration of the acyl group to the neighboring cis-O-3-hydroxyl in the natural product. However, study of our synthetic intermediates and prototypes indicate that the O-2 acyl group is quite stable, and that such migration does not occur readily

Synthesis and Reactivity of a Coordinatively Unsaturated Ruthenium(II) Parent Amido Complex: Studies of X−H Activation (X = H or C)

The five-coordinate parent amido complex (PCP)Ru(CO)(NH2) (2) (PCP = 2,6-(CH2PtBu2)2C6H3) has been prepared by two independent routes that involve deprotonation of Ru(II) ammine complexes. Complex 2 reacts with phenylacetylene to yield the Ru(II) acetylide complex (PCP)Ru(CO)(C⋮CPh) (5) and ammonia. In addition, complex 2 rapidly activates dihydrogen at room temperature to yield ammonia and the previously reported hydride complex (PCP)Ru(CO)(H). The ability of the amido complex 2 to cleave the H−H bond is attributed to the combination of a vacant coordination site for binding/activation of dihydrogen and a basic amido ligand. Complex 2 also undergoes an intramolecular C−H activation of a methyl group on the PCP ligand to yield ammonia and a cyclometalated complex. The reaction of (PCP)Ru(CO)(Cl) with MeLi allows the isolation of (PCP)Ru(CO)(Me) (8), and complex 8 undergoes an intramolecular C−H activation analogous to the amido complex 2 to produce methane and the cyclometalated complex. Determination of activation parameters for the intramolecular C−H activation transformations of 2 and 8 reveal identical ΔH⧧ {18(1) kcal/mol} with ΔS⧧ = −23(4) eu and −18(4) eu, respectively. Density functional theory has been applied to the study of intermolecular activation of methane and dihydrogen by (PCP‘)Ru(CO)(NH2) to yield (PCP‘)Ru(CO)(NH3)(X) (X = Me or H; PCP‘ = 2,6-(CH2PH2)2C6H3). The results indicate that the activation of dihydrogen is both exoergic and exothermic. In contrast, the addition of a C−H bond of methane across the Ru−NH2 bond has been calculated to be endoergic and endothermic. The surprising endoergic nature of the methane C−H activation has been attributed to a large and unfavorable change in Ru−N bond dissociation energy upon conversion from Ru-amido to Ru-ammine

Synthesis of a Malaria Candidate Glycosylphosphatidylinositol (GPI) Structure: A Strategy for Fully Inositol Acylated and Phosphorylated GPIs

A congener of the glycosylphosphatidylinositol (GPI) membrane anchor present on the cell surface of the malaria pathogen Plasmodium falciparum has been synthesized. This GPI is an example of a small number of such membrane anchors that carry a fatty acyl group at O-2 of the inositol. Although the acyl group plays crucial roles in GPI biosynthesis, it rarely persits in mature molecules. Other notable examples are the mammalian GPIs CD52 and AchE. The presence of bulky functionalities at three contiguous positions of the inositol moiety creates a very crowded environment that poses difficulties for carrying out selective chemical manipulations. Thus installations of the axial long-chain acyl group and neighboring phosphoglyceryl complex were fraught with obstacles. The key solution to these obstacles in the successful synthesis of the malarial candidate and prototype structures involved stereoelectronically controlled opening of a cyclic ortho ester. The reaction proceeds in very good yields, the desired axial diastereomer being formed predominantly, even more so in the case of long-chain acyl derivatives. The myoinositol precursor was prepared from methyl α-d-glucopyranoside by the biomimetic procedure of Bender and Budhu. For the glycan array, advantage was taken of the fact that (a) n-pentenyl ortho ester donors are rapidly and chemospecifically activated upon treatment with ytterbium triflate and N-iodosuccinimide and (b) coupling to an acceptor affords α-coupled product exclusively. A strategy for obtaining the GPI's α-glucosaminide component from the corresponding α-mannoside employed Deshong's novel azide displacement procedure. Thus all units of the glycan array were obtained from a β-d-manno-n-pentenyl ortho ester, this being readily prepared from d-mannose in three easy, high-yielding steps. The “crowded environment” at positions 1 and 2, noted above, could conceivably be relieved by migration of the acyl group to the neighboring cis-O-3-hydroxyl in the natural product. However, study of our synthetic intermediates and prototypes indicate that the O-2 acyl group is quite stable, and that such migration does not occur readily

Synthesis and Reactivity of a Coordinatively Unsaturated Ruthenium(II) Parent Amido Complex: Studies of X−H Activation (X = H or C)

The five-coordinate parent amido complex (PCP)Ru(CO)(NH2) (2) (PCP = 2,6-(CH2PtBu2)2C6H3) has been prepared by two independent routes that involve deprotonation of Ru(II) ammine complexes. Complex 2 reacts with phenylacetylene to yield the Ru(II) acetylide complex (PCP)Ru(CO)(C⋮CPh) (5) and ammonia. In addition, complex 2 rapidly activates dihydrogen at room temperature to yield ammonia and the previously reported hydride complex (PCP)Ru(CO)(H). The ability of the amido complex 2 to cleave the H−H bond is attributed to the combination of a vacant coordination site for binding/activation of dihydrogen and a basic amido ligand. Complex 2 also undergoes an intramolecular C−H activation of a methyl group on the PCP ligand to yield ammonia and a cyclometalated complex. The reaction of (PCP)Ru(CO)(Cl) with MeLi allows the isolation of (PCP)Ru(CO)(Me) (8), and complex 8 undergoes an intramolecular C−H activation analogous to the amido complex 2 to produce methane and the cyclometalated complex. Determination of activation parameters for the intramolecular C−H activation transformations of 2 and 8 reveal identical ΔH⧧ {18(1) kcal/mol} with ΔS⧧ = −23(4) eu and −18(4) eu, respectively. Density functional theory has been applied to the study of intermolecular activation of methane and dihydrogen by (PCP‘)Ru(CO)(NH2) to yield (PCP‘)Ru(CO)(NH3)(X) (X = Me or H; PCP‘ = 2,6-(CH2PH2)2C6H3). The results indicate that the activation of dihydrogen is both exoergic and exothermic. In contrast, the addition of a C−H bond of methane across the Ru−NH2 bond has been calculated to be endoergic and endothermic. The surprising endoergic nature of the methane C−H activation has been attributed to a large and unfavorable change in Ru−N bond dissociation energy upon conversion from Ru-amido to Ru-ammine

Ruthenium(II) Anilido Complexes TpRuL₂(NHPh): Oxidative 4,4‘-Aryl Coupling Reactions (Tp = Hydridotris(pyrazolylborate); L = PMe₃, P(OMe)₃, or CO)

Reactions of the Ru(II) amido complexes TpRuL2(NHPh) (L = CO, PMe3, or P(OMe)3) with AgOTf (OTf = trifluoromethanesulfonate) yield the binuclear complexes [TpRuL2NH(C6H4−)]2[OTf]2 along with the Ru(II) amine complexes [TpRuL2(NH2Ph)][OTf] in an approximate 1:1 molar ratio. In these reactions, the two ruthenium fragments are coupled via C−H bond cleavage and C−C bond formation at the para position of anilido ligands. A resonance structure corresponding to Ru(II) metal centers linked by a diimine ligand contributes significantly to the bonding. Evidence for such a contribution comes from the diamagnetic nature of the binuclear complexes and a solid-state X-ray crystallographic study of [TpRu{P(OMe)3}2NH(C6H4−)]2[OTf]2. It is proposed that the coupled products are formed via initial single-electron oxidation followed by C−C bond formation. Variable-temperature NMR spectra of the aryl-coupled complexes are consistent with two geometrical isomers around the rigid HN−C6H4−C6H4NH bridges

Ruthenium(II) Anilido Complexes TpRuL₂(NHPh): Oxidative 4,4‘-Aryl Coupling Reactions (Tp = Hydridotris(pyrazolylborate); L = PMe₃, P(OMe)₃, or CO)

Reactions of the Ru(II) amido complexes TpRuL2(NHPh) (L = CO, PMe3, or P(OMe)3) with AgOTf (OTf = trifluoromethanesulfonate) yield the binuclear complexes [TpRuL2NH(C6H4−)]2[OTf]2 along with the Ru(II) amine complexes [TpRuL2(NH2Ph)][OTf] in an approximate 1:1 molar ratio. In these reactions, the two ruthenium fragments are coupled via C−H bond cleavage and C−C bond formation at the para position of anilido ligands. A resonance structure corresponding to Ru(II) metal centers linked by a diimine ligand contributes significantly to the bonding. Evidence for such a contribution comes from the diamagnetic nature of the binuclear complexes and a solid-state X-ray crystallographic study of [TpRu{P(OMe)3}2NH(C6H4−)]2[OTf]2. It is proposed that the coupled products are formed via initial single-electron oxidation followed by C−C bond formation. Variable-temperature NMR spectra of the aryl-coupled complexes are consistent with two geometrical isomers around the rigid HN−C6H4−C6H4NH bridges