Reductive desulfurization of aromatic sulfides with nickel boride in deep eutectic solvent

In order to improve desulfurization rate, deep eutectic solvent (DES) was first used as the solvent in the reductive desulfurization process with nickel boride (NB). DES plays a dual roles...

Expanding the Scope of Asinger Chemistry towards Enantiomerically Pure Secondary Amines and β-Aminothiols through Chemoenzymatic Derivatization of 3-Thiazolines

A proof of concept for a novel approach towards enantiomerically highly enriched acyclic secondary amines and β-aminothiols as non-cyclic target molecules when starting from 3-thiazolines as heterocycles is presented. Starting from 2,2,4,5,5-pentamethyl-3-thiazoline, we demonstrated this chemoenzymatic pathway to both of these types of amine molecules, which were isolated as urea derivatives with a non-optimized yield of up to 20%. As a substrate, 2,2,4,5,5-pentamethyl-3-thiazolidine, which was obtained with an enantiomeric excess (ee) of 99% in a biotransformation from the corresponding 3-thiazoline according to a recently developed protocol, was used. For the reductive desulfurization of this substrate leading to a sulfur-free secondary amine, in situ formed Ni2B turned out to be a suitable reducing reagent. However, when using lithium aluminum hydride as a reducing agent, β-aminothiol was obtained.

Super electron donor-mediated reductive desulfurization reactions

The desulfurization of thioacetals and thioethers by a pyridine-derived electron donor is described.

The Johnson Synthesis of Paspaline

Paspaline 3, isolated from the ergot fungus Claviceps paspali, is a Maxi-K channel antagonist, and so a potential lead for the treatment of Alzheimer’s disease. The selec­tive C–H functionalization that converted 1 to 2 was a key step in the synthesis of 3 reported (J. Am. Chem. Soc. 2015, 137, 4968; J. Org. Chem. 2015, 80, 9740) by Jeffrey S. Johnson of the University of North Carolina. The prochiral diketone 4 was the starting point for the assembly of 1. Selective reduction with a commercial strain of yeast set both the relative and the absolute con­figuration of 5. The ketone interfered with the subsequent acid-catalyzed cyclization of the epoxy alcohol, so it was protected as the tosylhydrazone 6. This set the stage for the direct Bamford– Stevens conversion to the fully-substituted alkene 7. Ireland–Claisen rearrangement of the isobutyrate derived from 7 proceeded with substantial preference for the equatorial diastereomer 8. This was carried on to the methyl ketone 9. Hydroboration of 9 showed substantial axial preference, to deliver, after oxidation, the equatorial aldehyde 10. Intramolecular aldol condensation to 11 followed by hydrogenation and benzyl oxime formation then completed the preparation of 1. Intramolecular Pd-catalyzed acetoxylation has been extensively studied by Sanford (Org. Lett. 2010, 12, 532). The Sanford conditions, carried out on a gram scale, conver­ted 1 into the equatorial diastereomer 2 with remarkable diastereoselectivity. The final carbocyclic ring was then added by vinyl Grignard addition to the derived keto alde­hyde 12. Grubbs cyclization gave 13, that on exposure to acid rearranged to the enone 14. Reduction of the ketone occurred from the open face to give an alcohol that then directed hydrogenation from the opposite face, leading to the desired trans-fused ketone. Sulfenylation then completed the synthesis of the ketone 15. At this point, the authors followed Smith (J. Am. Chem. Soc. 1985, 107, 1769) in using the Gassman protocol (J. Am. Chem. Soc. 1974, 96, 5495) to construct the indole. Amination of the sulfur of 15 with N-chloroaniline gave the sulfonium salt, that on exposure to Et3N rearranged to 16. Reductive desulfurization followed by cyclization completed the synthesis of paspaline 3.

Synthesis of 1,5-Anhydro-d-glycero-d-gluco-heptitol Derivatives as Potential Inhibitors of Bacterial Heptose Biosynthetic Pathways

A series of 1,5-anhydro-d-glycero-d-gluco-heptitol derivatives have been prepared from 3-O-benzyl-1,2-O-isopropylidene-d-glycero-d-gluco-heptofuranose via conversion into anomeric bromide and thiophenyl derivatives, followed by glycal formation and reductive desulfurization, respectively. Global deprotection of the protected intermediates afforded the 1,5-anhydro derivatives of the d-glycero-d-gluco- and 1,2-dideoxy-d-altro- configuration as well as the 1,5-anhydro-2-deoxy-d-altro-hept-1-enitol. In addition, the 7-O-phosphorylated d-glycero-d-gluco-heptose and its 1,5-anhydro analogue were prepared in good yields utilizing phosphoramidite chemistry. A novel heptitol analogue based on a 1-deoxynojirimycin scaffold was also elaborated via a Wittig­-type chain elongation followed by dihydroxylation, separation of the resulting epimers, and global deprotection. The target compounds, however, were not active as inhibitors of the bacterial sedoheptulose-7-phosphate isomerase GmhA.