IV-Acyliminium ions

Formation of a vinyl-substituted pyrrolizidine derivative is also observed in case of an allylstan-nane cyclization94. Since the allylstannane moiety is acid sensitive, the iV-acyliminium ion is generated by exposure of the hydroxylactam to methanesulfonyl chloride and triethylamine in dichloromethane. The very rapid cyclization produces the endo-vinyl compound with very high stereoselectivity. 

Stereoselective reactions of this type known at present only deal with four- or five-membered cyclic iV-acyliminium ions. The reactions with carbon nucleophiles usually lead to rra/u-substi-tuted compounds with very high stereoselectivity due to steric control by the substituent already present in the ring. 

Very similar transformations have been reported by using titanium enolates of chiral thiazolidine-2-thiones or oxazolidine-2-ones in combination with various in r// -generated acyclic or cyclic iV-acyliminium ions as electrophiles.110-112... 

When the pyrrolo[l,2-c]oxazole 269 was treated with trimethyl orthoformate in the presence of BF3 Et20, in dichloromethane at — 78 °C, a mixture of compounds was obtained from which the expected 5-dimethoxymethyl derivative, 270, was isolated in poor yield (12%) with another dimethoxylated compound 271 (23%). The formation of 271 could be explained by the addition of the formyl cation equivalent at C-7, followed by the protonation at C-6 of the resulting enamide 272 leading to the electrophilic iV-acyliminium ion 273 (Scheme 40). The regioselectivity of this electrophilic addition of trimethylorthoformate to the silyloxypyrrole 269 at C-7, in a non-vinylogous manner, is unusual <1999TL2525>. 

Treatment of a-hydroxy- or a-alkoxy-substituted hexahydro-oxazolo[3,4-r ]pyridin-3-ones with an acid allows for the generation of bicyclic iV-acyliminium ions which can then smoothly react with nucleophiles, usually with high diastereoselectivities (Scheme S3) <2001EJ01267, 1998SL206>. 

The reactions did prove to be compatible with the use of a-stannyl amides. In these cases, the cyclization reaction involved the trapping of an iV-acyliminium ion by the olefin and led to the formation of substituted piperidines. 

The domino cycloaddition-iV-acyliminium ion cyclization cascade has been extensively reviewed. Tandem reactions combining Diels-Alder reactions and sigma-tropic rearrangement reactions in organic synthesis have been extensively reviewed. The tandem Diels-Alder reaction between acetylenedicarboxaldehyde and N,N -dipyrrolylmethane has been extensively studied at the RHT/3-21G and RHF/6-31G levels.The molecular mechanism of the domino Diels-Alder reaction between hexafluorobut-2-yne and A,A -dipyrrolylmethane has been studied using density functional theory. 

Overman and co-workers have reported Mannich bis-cyclizations (carboxylate-terminated iV-acyliminium ion bis-cyclizations Scheme 56) and employed these in the total synthesis of (—)-ajmalicine <1995JA9139>. 

The reaction of 2,4-pentadienyltrimethylsilane with IV-acyliminium ion generated in situ at —78°C results in the formation of pentadienyl-substituted lactams 87 in good yield (equation 59). It is noted that the reaction temperature is an important factor for controlling the e-regioselectivity. A mixture of e- and /-substitution products at the dienyl system is obtained when the reaction is carried out at 0 °C127. 

The ring-opening reaction on 4-methyl-2-thia-7-aza-tricyclo[5.3.0.01,4]decan-8-one 39 was carried out by treatment with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) <20010L1781, 2004JOG33>. Methylthiolation of the thietane sulfur produces a transient alkylthiosulfonium salt which easily dissociates to the iV-acyliminium ion 40. Once formed, 40 readily undergoes loss of a proton to give the product 40 (Equation 11). 

A domino reaction catalyzed by AlMe3 leads to the skeleton of the Erythrina and /3-homo-/<.ry thrift a alkaloids (Scheme 49) <2004AGE5391>. The mechanism is believed to proceed via an iV-acyliminium ion and a metalled amide. 

The formation of activated iminium intermediates derived from nitrogen heterocycles has been reported by Comins and co-workers.163,163a The activation of pyridine derivative with phenyl chloroformate provides pyridinium salt, which smoothly reacts with the zinc homoenolate (Equation (94)).163 163a 164 The reaction of unsaturated amide with Ph jC 1 BI 4 produces iV-acyliminium ions, which react with PhaZn in CH2CI2 producing the desired a--substituted amine (Equation (95)).165... 

In almost any case of in situ production of iV-acyliminium ions from an aldehyde and a nitrile, a mixture of mineral acid with glacial acetic acid serves as the acid catalyst5-7. Probably the acetic acid is the source of the acylium ions which are necessary for the activation of carbonyl component (see Section III.B.3). 

In an example of a C-C bond formation in the construction of a 1,4-diazocine ring, racemic [2,5]benzodiazocines 67 were synthesized from hydroxylactams 66 via an iV-acyliminium ion-pyrrole cyclization reaction (Scheme 9) <2000H(52)273>. 

The iV-acyliminium ion can be characterized by FTIR spectroscopy as well. The starting carbamate 1 exhibited an absorption at 1694 cm due to the carbonyl stretching, while the A -acyliminium ion 2 generated by the cation pool method exhibited an absorption at 1814 cm". The higher wave number observed for the cation is consistent with the existence of a positive charge at the nitrogen atom adjacent to the carbonyl carbon. The shift to higher wave number is also supported by DFT (density functional theory) calculations. 

Formation of iV-acyliminium ion under mild and almost neutral conditions makes a marked contrast to conventional methods where N-acyliminium ions are generated under acidic conditions from... 

An efficient enantiodivergent synthesis of levorotatory (lS,2/ ,8aS>l,2-dihydroxyindolia e (62a) and its antipode (62b) has been developed starting from commercially available o-isoascoibic acid (61 Scheme 27). This strategy illustrates the complementary use of iminium and IV-acyliminium ion inter-... 

Many of these reactions occur with formation of A -acyliminium ions 2 as intermediates (equation 1), which give the enamides after elimination of the electrofuge from -carbon atom, or the A-acylimines by removal of R group from nitrogen atom. In that way, the iV-acyliminium ions 2 appear not only as the intermediates in acid-catalyzed conversions of enamides but also as direct precursors of the latter, In other words, the chemistry of enamides and their A-acylimine tautomers is closely connected with A -acyliminium chemistry, a topic which has been reviewed comprehensively ... 

During the amidoalkylation of olefins 16 by their addition to the iV-acyliminium ions 17, the products can undergo cyclization by a polar 1,4-cycloaddition . 

Padwa ° has concisely summarized his domino cycloaddition/iV-acyliminium ion cyclization cascade process—a tactic akin to a two-move chess combination— involving the generation of an isomunchnone 1,3-dipole, intramolecular 1,3-dipolar cycloaddition reaction, A -acyliminium ion formation, and Mannich cyclization. 

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