Academic literature on the topic 'N-tosylhydrazones'

The reduction of pyridines offers an attractive approach to piperidine synthesis, and now Toshimichi Ohmura and Michinori Suginome of Kyoto University have developed (J. Am. Chem. Soc. 2012, 134, 3699) a rhodium-catalyzed hydroboration of pyridines, including the reaction of 1 to produce 3. Timothy J. Donohoe at the University of Oxford has found (Org. Lett. 2011, 13, 2074) that pyridinium silanes 4 undergo intramolecular hydride transfer by treatment with TBAF to produce dihydropyridones (e.g., 5) with good diastereoselectivity. Enantioselective amination of allylic alcohols has proven challenging, but Ross A. Widenhoefer at Duke University has reported (Angew. Chem. Int. Ed. 2012, 51, 1405) that a chiral gold catalyst can effect such intramolecular cyclizations with good enantioselectivity, as in the synthesis of 7 from 6. Alternatively, Masato Kitamura at Nagoya University has developed (Org. Lett. 2012, 14, 608) a ruthenium catalyst that operates at as low as 0.05 mol% loading for the conversion of substrates such as 8 to 9. Efforts to replace transition metal catalysts with alkaline earth metal-based alternatives have been gaining increasing attention, and Kai C. Hultzsch at Rutgers University has found (Angew. Chem. Int. Ed. 2012, 51, 394) that the magnesium complex 12 is capable of catalyzing intramolecular hydroamination (e.g., 10 to 11) with high enantioselectivity. Meanwhile, a stereoselective Wacker-type oxidation of tert-butanesulfinamides such as 13 to produce pyrrolidine derivatives 14 has been disclosed (Org. Lett. 2012, 14, 1242) by Shannon S. Stahl at the University of Wisconsin at Madison. Though highly desirable, Heck reactions have rarely proven feasible with alkyl halides due to competitive β-hydride elimination of the alkyl palladium intermediates. Sherry R. Chemler at the State University of New York at Buffalo has demonstrated (J. Am. Chem. Soc. 2012, 134, 2020) a copper-catalyzed enantioselective amination Heck-type cascade (e.g., 15 and 16 to 17) that is thought to proceed via radical intermediates. David L. Van Vranken at the University of California at Irvine has reported (Org. Lett. 2012, 14, 3233) the carbenylative amination of N-tosylhydrazones, which proceeds through η3-allyl Pd intermediates constructed via carbene insertion. This chemistry was applied to the two-step synthesis of caulophyllumine B from vinyl iodide 18 and N-tosylhydrazone 19.

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.