Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

• Published in: Journal of organic chemistry Vol. 78; no. 12; pp. 5832 - 5842
• Main Authors: Mola, Laura, Font, Joan, Bosch, Lluís, Caner, Joaquim, Costa, Anna M, Etxebarría-Jardí, Gorka, Pineda, Oriol, de Vicente, David, Vilarrasa, Jaume
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.06.2013; Amer Chemical Soc
• Subjects: Alkynes - chemistry; Amines; Catalitzadors; Catalysis; Catalysts; Chemical tests and reagents; Chemistry; Chemistry, Organic; Electrons; Imides - chemistry; Inosine - chemistry; Lactames; Lactams; Lactams - chemistry; Molecular Structure; Morpholines - chemistry; Nucleosides; Nucleosides - chemistry; Nucleòsids; Organic synthesis; Physical Sciences; Piperazines - chemistry; Propionates - chemistry; Proves i reactius químics; Pyridines - chemistry; Pyridones - chemistry; Pyrimidines - chemistry; Quantum Theory; Science & Technology; Stereoisomerism; Síntesi orgànica; Zidovudine - analogs & derivatives; Zidovudine - chemistry; ACETYLENIC ESTERS; ACID-DERIVATIVES; STRATEGY; RADICAL CYCLIZATION; BAYLIS-HILLMAN REACTION; ALPHA-ADDITION; MORPHOLINE; STEREOSELECTIVE-SYNTHESIS; ALKYNES; AMIDES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo4006409

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.