Academic literature on the topic 'Desulfonylation'

The pentacyclic Apocynaceae alkaloid aspidophylline A 3 reverses drug resistance in resistant KB cells. In developing a strategy for the assembly of 3, Neil K. Garg of UCLA envisioned (J. Am. Chem. Soc. 2011, 133, 8877) the intramolecular Pd-catalyzed cyclization of 1 to 2. The starting material for the cyclohexenone derivative 1 was the known tricyclic anhydride 7. This was readily available in gram quantities by oxidation of the commercial pyridone 4. The double decarboxylation to 8 was delicate but could be effected by iterative small-batch microwave heating. Protection of 8 followed by fragmentation and alkylation than delivered 1. The intramolecular Heck cyclization of 1 indeed proceeded smoothly, giving the bicyclic diene 2. Deprotection of the ketone revealed a doubly activated enone, which could be selectively reduced under modifi ed dissolving metal conditions to give the keto ester 12. Alkylation of the lithium enolate with allyl iodide then gave 13, predominantly as the diastereomer illustrated. Reduction followed by selective Johnson-Lemieux oxidative cleavage of the terminal alkene then completed the construction of the diol 14. The vision for the final assembly of the alkaloid was to effect interrupted Fischer indolization of an alkylated cyclohexanone such as 15. To this end, several bicyclic ketones were explored, but none was successful. Finally, attention was turned to the more rigid tricyclic lactone 15. Happily, exposure of 15 to phenylhydrazine in the presence of trifluoroacetic acid led to an intermediate that was not isolated, but directly combined with methanolic K2CO3 to open the lactone, allowing closure of the tetrahydrofuran ring, to give 16. Simple arene sulfonamides can be advantageous in synthesis, as they do not appear as rotameric mixtures in NMR, and are often crystalline. Nevertheless, they have not commonly been used because of the perceived difficulty of deprotection. Sonication of 16 with Mg powder in methanol containing solid NH4Cl led to smooth desulfonylation. Formylation then completed the synthesis of aspidophylline A 3.

Sentaro Okamoto of Kanagawa University developed (Tetrahedron Lett. 2014, 55, 7039) an organocatalyst that mediated the selective acylation of 1 to give the pri­mary acetate 2. Philip A. Albiniak of Ball State University devised (Tetrahedron Lett. 2014, 55, 7133) a reagent 4 for the simple preparation of a t-butyl ether 5 from an alcohol 3. Attempted deprotection of 6 tended to divert to the dioxolane. Toshio Nishikawa of Nagoya University developed (Synlett 2014, 25, 2498) an oxidative protocol that gave clean conversion to the desired 7. Alan S. Goodman of Rutgers University found (Angew. Chem. Int. Ed. 2014, 53, 10160) an Ir catalyst that generated the phenol 9 from the aryl alkyl ether 8. In the course of a synthesis of Sch 725674, Kavirayani R. Prasad of the Indian Institute of Science, Bangalore deprotected (Org. Lett. 2014, 16, 4001) the dithi­ane 10 to yield the sensitive aldol product 11. Karl Anker Jørgensen of Aarhus University observed (Chem. Commun. 2014, 50, 15689) that the nitro isoxazole 12, having served to activate sequential Michael addition, was readily cleaved to the acid 13. Jiang Cheng of Changzhou University used (Chem. Commun. 2014, 50, 8412) CuCN to convert 14 to 15. Pradeep Kumar of CSIR-National Chemistry Laboratory effected (Tetrahedron Lett. 2014, 55, 7172) oxidative deallylation of 16, leading to 17. Hiroyuki Morimoto and Takashi Ohshima of Kyushu University found (Chem. Commun. 2014, 50, 12623) that NH₄I promoted the hydrazinolysis of the amide 18, giving 19 without racemization. Franco Ghelfi of the Università degli Studi di Modena e Reggio Emilia prepared (Eur. J. Org. Chem. 2014, 6734) 21 by desulfonylating 20 to 21 with H₂SO₄ in acetic acid. Hans Adolfsson of Stockholm University reduced (Org. Lett. 2014, 16, 680) the amide 22 to the enamine 23. The N-vinyl amine could be hydrolyzed, but it is also a versatile intermediate for other transformations. Automated peptide synthesis can be hindered by difficult sequences. Judit Tulla-Puche and Fernando Albericio of IRB Barcelona showed (Chem. Eur. J. 2014, 20, 15031) that the substituted benzyl group of 24 facilitated such syntheses, and that it could be readily removed to give 25 by exposure to NH₄I and trifluoroacetic acid.