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

Abstract

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, Npropynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, secondly, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl 3 , RuClCp*(PPh 3 ) 2 , AuCl, AuCl(PPh 3 ), CuI, and Cu 2 (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.

Extremely Rapid Polythioether Synthesis in the Presence of TBD

“…The polymerization in the final step starts by abstracting a proton from the thiol-end by TBD. Since organobase having sufficient nucleophilicity has a huge affinity toward the electron-deficient alkyne groups, − it is also reasonable to suggest another mechanism for the polymerization. Route 2 deals with the strong nucleophilic character of TBD.…”

Phosphazene Catalyzed Addition to Electron-Deficient Alkynes: The Importance of Nonlinear Allenyl Intermediates upon Stereoselectivity

“…20 Control of the alkene E/Z-stereochemistry is essential for such a reaction; however, stereoselective organocatalytic examples are relatively scarce. With nucleophilic organocatalysts such as tertiary amines [21][22][23] or phosphines, [23][24][25] the thermodynamically more stable (E)-olefin product dominates. A similar result is obtained with phase-transfer organocatalysts developed by Maruoka.…”

Total Synthesis of Spirotryprostatins through Organomediated Intramolecular Umpolung Cyclization

“…We decided to explore a sequential procedure involving Grignard‐addition‐dehydration‐Friedel–Crafts reactions to form the prenyl moiety and the C ‐ring together. Treatment of 40 a and 40 b with 3‐butyn‐2‐one in the presence of 4‐dimethylaminopyridine (DMAP) provided 41 a and 41 b in excellent yields (Scheme ) . For electron‐rich compound 41 b , addition of MeMgBr followed by acid‐induced cyclization gave 11 b in 76 % yield.…”

“…We decidedt oe xplore as equential procedure involving Grignardaddition-dehydration-Friedel-Crafts reactions to form the prenyl moiety and the C-ring together.T reatment of 40 a and 40 b with 3-butyn-2-onei nt he presence of 4-dimethylaminopyridine (DMAP) provided 41 a and 41 b in excellent yields (Scheme 5). [17] For electron-rich compound 41 b,a ddition of MeMgBrf ollowed by acid-induced cyclization gave 11 b in 76 %y ield. For intermediate 41 a,a lthough ao ne-pot procedure could lead to desired 11 a in 25 %y ield, bettery ield (73 %, two steps) could be obtained by treatment of 42 a,t he isolated pure adduct, in acetonitrile with p-toluenesulfonic acid monohydrate.…”