Formaldiminium ion

Potential energy curves, ethylene. 66. 373 diatomic molecule. 36. 239 formaldimine, 374-75 formaldiminium ion. 373 molecular oxygen. 478-79 SiH, elimination, 394... 

The present procedure illustrates the use of added iodide anion to promote the Mannich cyclization of an alkyne to afford 3-alkylidenepiperidines. As illustrated in Table I a variety of nonbasic nucleophiles with nucleophilic constants T1-CH3I >5.8 are useful promoters of formaldiminium ion-alkyne cyclizations. Piperidines containing both endocyclic and exocyclic allylic unsaturation can be efficiently assembled in this way from readily available alkynol precursors (see Table 1). To the limits of f H NMR detection at 500 MHz all nucleophile-promoted cyclizations that form... 

The formaldiminium ion formed from the reaction of 4-hexynylamine (90 R = R = Me) with paraformaldehyde and camphorsulfonic acid is reported not to cyclize when heated for 1 h at 1(X) C in the weakly nucleophilic solvent acetonitrile. However, when nucleophilic salts are added the 3-alkylidene-piperidines (91) are formed in good yields (Scheme 32). Attempted cyclizations of (90) in the presence of weaker nucleophiles such as benzenethiol or methanol were less effective, the former yielding <15% of the expected alkylidenepiperidine product, while the latter provided no products of cyclization. If the strong nucleophile iodide is employed, even a weakly nucleophilic terminal alkyne can be successfully cyclized. In all of these cyclizations of 4-alkynylamines only formation of a six-membered ring product was observed. The (2)-stereochemistry of the alkylidene side chain evolves from antarafacial addition of the internal iminium cation and the external nucleophile to the alkyne. 

A study of 3-alkynylamines (92) addressed the question of endocyclic versus exocyclic ring closure in nucleophile-assisted alkyne cyclizations (equation 9). Cyclizations of the formaldiminium ion derived from (92) occurred only in the endocyclic sense affording tetrahydropyridines (93). Terminal as well as substituted alkynes were observed to react with endocyclic regioselectivity in the presence of a variety of nucleophiles. 

The pronounced sensitivity of alkynes to cyclization in the presence of external nucleophiles is illustrated in studies of formaldiminium ion (99) in which an alkyne and alkene compete as intramolecular ir-nucleophiles. While cyclization of (99) in water afforded 4-hydroxypiperidine (98) in 73% yield, cyclization in the presence of 10 equiv. of Nal gave vinyl iodide (100) in 76% yield (Scheme 34). It has been suggested that the mechanism of these nucleophile-promoted iminium ion-alkyne cyclizations probably involves rate-determining attack of the nucleophile on a ir-complex or bridged cation produced from reversible interaction of the iminium ion and alkyne groups. ... 

Simple alkynes do not undergo intramolecular reactions with weakly electrophilic iminium ions in the absence of strong external nucleophiles.3 For example, the formaldiminium ion derived from 4-hexynylamine, formaldehyde, and... 

Overman s retrosynthetic analysis is depicted in Scheme 1. Pentacyclic ketone 4, derived from allylic alcohol 7 by an aza-Cope-Mannich rearrangement of formaldiminium ion derivative 6 furnished 3 through the C5 hemiketal disconnection. An intramolecular oxidative coupling of a dienolate generated from indole-... 

The Pd-catalysed addition of boronic acids to homopropargylic amines (93), carried out in the presence of formaldehyde, is believed to proceed via the Pd-coordinated formaldiminium ions (94), affording )V-alkyl-3-alkylidenepyrrolidines (95) as a result of the overall iyn-addition across the C=C bond. " ... 

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