Synthesis of the Salmonella Type E₁ Core Trisaccharide as a Probe for the Generality of 1-(Benzenesulfinyl)piperidine/Triflic Anhydride Combination for Glycosidic Bond Formation from Thioglycosides

A synthesis of a chromogenic glycoside of the Salmonella anatum group E1 core trisaccharide is presented in which all three glycosidic bonds, a 1,2-cis-equatorial, a 1,2-trans-axial, and a 1,2-trans-equatorial linkage representing three of the four main classes of glycosidic bond, are formed with thioglycoside donors activated under a single set of conditions by the combination of 1-(benzenesulfinyl)piperidine and trifluoromethanesulfonic anhydride. 2,3-O-Carbonyl- and 2,3-O-isopropylidene-α-l-rhamnopyranosyl thioglycosides are found to be highly α-selective rhamnosyl donors under these conditions

Direct Stereoselective Synthesis of β-Thiomannosides

A highly diastereoselective synthesis of β-thiomannopyranosides is described in which S-phenyl 2,3-di-O-benzyl-4,6-O-benzylidene-1-deoxy-1-thia-α-d-mannopyranoside S-oxide is treated with triflic anhydride and 2,6-di-tert-butyl-4-methylpyridine in CH2Cl2 at −78 °C leading to the formation of an intermediate α-mannosyl triflate. Addition of primary, secondary, or tertiary thiols then leads to the β-thiomannosides, by an SN2-like displacement, in good yield and with excellent stereoselectivity. Deprotection is achieved either by Birch reduction or by Zemplen deacetylation, of the acetyl protected aglycons, followed by hydrogenolysis over Pearlman's catalyst. The assignment of configuration of the β-thiomannopyranosides is discussed in terms of the chemical shift of the mannose H5 resonance and the 1JCH of the mannose anomeric carbon

Catalytic Asymmetric Vinylation and Dienylation of Ketones

A solution to the long-standing problem of catalytic asymmetric vinylation of ketones is reported. Vinylzinc reagents are generated via hydrozirconation of terminal alkynes followed by transmetalation to zinc. In the presence of our catalyst, which is formed in situ from a bis(sulfonamide) diol ligand (1) and titanium tetraisopropoxide, the vinylzinc reagent undergoes 1,2-addition to a variety of ketones and enones with enantioselectivities (typically >90%) and high yields. This method is tolerant of functional groups, including alkyl, aryl and vinyl halides, esters, silyl protected alcohols, sulfides, and alkenes. Thus, enantioenriched tertiary allylic alcohols bearing a variety of functional groups can be prepared. It has also been found that 2,2-disubstituted vinylzinc reagents, substitution patterns not accessible through hydrozirconation, can be added to ketones with high enantioselectivities to generate trisubstituted allylic alcohols. Furthermore, we have developed an asymmetric addition of dienyl groups to ketones in the presence of our catalyst. This method enables the synthesis of dienols in high yields with enantioselectivities as high as 94%

Catalytic Asymmetric Vinylation and Dienylation of Ketones

A solution to the long-standing problem of catalytic asymmetric vinylation of ketones is reported. Vinylzinc reagents are generated via hydrozirconation of terminal alkynes followed by transmetalation to zinc. In the presence of our catalyst, which is formed in situ from a bis(sulfonamide) diol ligand (1) and titanium tetraisopropoxide, the vinylzinc reagent undergoes 1,2-addition to a variety of ketones and enones with enantioselectivities (typically >90%) and high yields. This method is tolerant of functional groups, including alkyl, aryl and vinyl halides, esters, silyl protected alcohols, sulfides, and alkenes. Thus, enantioenriched tertiary allylic alcohols bearing a variety of functional groups can be prepared. It has also been found that 2,2-disubstituted vinylzinc reagents, substitution patterns not accessible through hydrozirconation, can be added to ketones with high enantioselectivities to generate trisubstituted allylic alcohols. Furthermore, we have developed an asymmetric addition of dienyl groups to ketones in the presence of our catalyst. This method enables the synthesis of dienols in high yields with enantioselectivities as high as 94%

Catalytic Asymmetric Vinylation of Ketones

This communication describes the catalytic asymmetric 1,2-addition of vinylzinc reagents to aromatic, α,β-unsaturated, and dialkyl ketones with enantioselectivities between 79 and 97% and with yields ranging from 84 to 98%. The products of these reactions are tertiary allylic alcohols with chiral quaternary centers that are useful in organic synthesis. The reaction involves hydrozirconation of a terminal alkyne, transmetalation to zinc, and addition to a ketone in the presence of a chiral titanium-based Lewis acid catalyst. The reactions proceed smoothly at room temperature in under 24 h

Direct Chemical Synthesis of the β-Mannans: Linear and Block Syntheses of the Alternating β-(1→3)-β-(1→4)-Mannan Common to <i>Rhodotorula </i><i>glutinis</i>, <i>Rhodotorula </i><i>mucilaginosa</i>, and <i>Leptospira </i><i>biflexa</i>

Two stereocontrolled syntheses of a methyl glycoside of an alternating β-(1→4)-β-(1→3)-mannohexaose, representative of the mannan from Rhodotorula glutinis, Rhodotorula mucilaginosa, and Leptospira biflexa, are described. Both syntheses employ a combination of 4,6-O-benzylidene- and 4,6-O-p-methoxybenzylidene acetal-protected donors to achieve stereocontrolled formation of the β-mannoside linkage. The first synthesis is a linear one and proceeds with a high degree of stereocontrol throughout and an overall yield of 1.9%. The second synthesis, a block synthesis, makes use of the coupling of two trisaccharides, resulting in a shorter sequence and an overall yield of 4.4%, despite the poor selectivity in the key step

Generation and Tandem Reactions of 1-Alkenyl-1,1-Heterobimetallics: Practical and Versatile Reagents for Organic Synthesis

A practical and straightforward method for generation of versatile 1-alkenyl-1,1-heterobimetallic intermediates and their application to construction of functionalized building blocks are disclosed. Beginning with readily available air-stable 1-alkynyl-1-boronate esters, hydroboration with dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In situ transmetallation with dialkylzinc reagents furnishes 1-alkenyl-1,1-heterobimetallic intermediates. Direct treatment with aldehydes followed by workup allows isolation of B(pin)-substituted allylic alcohols in 70−95% yield. The B(pin)-substituted allylic alcohols react with NBS to afford (E)-α,β-unsaturated aldehydes in 51−77% yield via a semipinacol-type rearrangement. In situ treatment of 1-alkenyl-1,1-heterobimetallic intermediates with aldehydes followed by TBHP oxidation enables the preparation of α-hydroxy ketones. Under optimized conditions, addition of 1-alkenyl-1,1-heterobimetallic intermediates to a variety of protected α- and β-hydroxy aldehydes proceeds with good to excellent control over diastereoselectivity to furnish differentially protected dihydroxy ketones. The 1-alkenyl-1,1-heterobimetallic intermediates have also been employed in tandem aldehyde addition/Suzuki cross-coupling reactions to provide densely functionalized allylic alcohols in good to excellent yields

Generation and Tandem Reactions of 1-Alkenyl-1,1-Heterobimetallics: Practical and Versatile Reagents for Organic Synthesis

A practical and straightforward method for generation of versatile 1-alkenyl-1,1-heterobimetallic intermediates and their application to construction of functionalized building blocks are disclosed. Beginning with readily available air-stable 1-alkynyl-1-boronate esters, hydroboration with dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In situ transmetallation with dialkylzinc reagents furnishes 1-alkenyl-1,1-heterobimetallic intermediates. Direct treatment with aldehydes followed by workup allows isolation of B(pin)-substituted allylic alcohols in 70−95% yield. The B(pin)-substituted allylic alcohols react with NBS to afford (E)-α,β-unsaturated aldehydes in 51−77% yield via a semipinacol-type rearrangement. In situ treatment of 1-alkenyl-1,1-heterobimetallic intermediates with aldehydes followed by TBHP oxidation enables the preparation of α-hydroxy ketones. Under optimized conditions, addition of 1-alkenyl-1,1-heterobimetallic intermediates to a variety of protected α- and β-hydroxy aldehydes proceeds with good to excellent control over diastereoselectivity to furnish differentially protected dihydroxy ketones. The 1-alkenyl-1,1-heterobimetallic intermediates have also been employed in tandem aldehyde addition/Suzuki cross-coupling reactions to provide densely functionalized allylic alcohols in good to excellent yields

A Divergent and Selective Synthesis of Isomeric Benzoxazoles from a Single N–Cl Imine

A divergent and regioselective synthesis of either 3-substituted benzisoxazoles or 2-substituted benzoxazoles from readily accessible ortho-hydroxyaryl N–H ketimines is described. The reaction proceeds in two distinct pathways through a common N–Cl imine intermediate: (a) N–O bond formation to form benzisoxazole under anhydrous conditions and (b) NaOCl mediated Beckmann-type rearrangement to form benzoxazole, respectively. The reaction path also depends on the electronic nature of the aromatic ring, with the electron-rich aromatic rings favoring the rearrangement and the electron-deficient rings favoring the N–O bond formation. A Beckmann-type rearrangement mechanism via net [1,2]-aryl migration for the formation of 2-substituted benzoxazole is proposed

Electrochemical Probing the Site Reactivity in Iron Single-Atom Catalysts for Electrocatalytic Nitrate Reduction to Ammonia

Single-atom catalysts (SACs), specifically iron single atoms dispersed on nitrogen-doped carbon (Fe-NC), have shown promising potential in the electrocatalytic reduction of nitrate to ammonia (NitRR), but there is a lack of understanding of their intrinsic activity. The conventional measurements often overlook the intrinsic performance of SACs, leading to significant underestimation. This study presents an in situ electrochemical probing protocol, using two poisoning molecules (SCN– and NO2–), to characterize the reactivity of Fe sites in Fe-NC SACs for NitRR. The technique aids in quantifying the yield rate of ammonia on Fe sites and the active site number. The findings reveal the intrinsic turnover frequency (TOF) based on the number and ammonia yield rate of Fe sites, challenging the current understanding of SACs’ inherent performances. This unique approach holds considerable potential for determining the intrinsic activity of other SACs in complex reactions, opening new avenues for the exploration of electrocatalytic processes