Acid-catalysed formation of tricyclic N,S-acetals in imidazolinone series based on the use of the unprecedented N-acyliminium ion cascade reaction involving transposition, heterocyclisation and π-cyclisation

Abstract

4-Hydroxy-5,5-dimethylimidazolines tethered at N-1 to an aryl sulfide undergo an unprecedented acid-catalysed domino reaction, involving double methyl transposition, heterocyclisation, isomerisation of thiazetidinium ion and, finally, pi-cyclisation. In this way a one-pot synthesis of original tricyclic N,S-acetals was developed. The same triheterocyclic products can be prepared also starting from the corresponding 5-hydroxy isomers (in this case the cascade of reactions does not involve methyl transposition).

Use of the cascade α-oxo-amidoalkylation/transposition/ p-cationic cyclization of N-acyliminium ions in the synthesis of novel fused heterocyclic N,O-acetals

“…7 Later, after optimization work using LAH, 8 NaBH 4 , 9 etc., the regioselective reduction of the resultant imides 10a-c was performed with a large excess of NaBH 4 (6 equiv.) in analogy to our reports for related structures 5 and others 9 to afford α-hydroxy lactams 4a-c in good yields (67%, 75% and 96%, respectively; see Scheme 2). In some cases, to avoid the relatively poor solubility of the starting imides 10 and the laborious work-up encountered during these processes, a small quantity of THF was added as co-solvent.…”

“…For this purpose, the α-hydroxy lactam 12 that we described recently 5 was considered. Thus, treatment of 12 in neat TFA in precise amount to the reactant (1.5 mL per 1 mmol of 12) provided the product 15 exclusively.…”

“…In the framework of our interest in intramolecular cationic cyclizations based on the formation and cleavage of carbon-heteroatom linkages for the preparation of complex N,Xcontaining heterocycles, we have recently demonstrated that in acidic media α-hydroxy lactams of type 1 are effective precursors of the tricyclic N,S-acetals 2 (Scheme 1). 5 These cyclized products are the result of the exclusive intramolecular attack of the sulfur atom onto the endocyclic N-acyliminium ion intermediates into A, their opening into B, followed by π-cationic cyclization into the polysubstituted tricyclic N,S-acetals 2. It is important to note that, whatever the experimental conditions used during these investigations, no formation of the direct π-cationic cyclization products 3 was observed.…”

Methods for the synthesis of 1-substituted 1H-imidazol-2(3H)-ones

“…60 It was shown that the initially formed hydroxyimidazolidinone 32b underwent a peculiar acid-catalyzed reaction in the presence of p-TsOH, involving a methyl group transfer and elimination of water molecule, resulting in the formation of imidazolone 1aa. The synthesis of 1-substituted 1H-imidazol-2(3H)-ones from imidazolidine-2,4-diones (hydantoins) was first described already in 1950.…”

Strategies Based on Aryllithium and N‐Acyliminium Ion Cyclizations for the Stereocontrolled Synthesis of Alkaloids and Related Systems

“…was used, only the direct arylation reaction occurred, leading to 37, probably due to diminished nucleophilicity of the sulfur atom as a result of coordination to the Lewis acid (Scheme 11). [27] In this context, bismuth(III) triflate has been found to promote the formation of cyclic acyliminium ions in remarkably low amounts (1 mol-%), suitable for both inter- and intramolecular reactions. [28] As depicted in Scheme 12, Bi(OTf) 3 -catalyzed intramolecular cyclizations of the acetoxylactams 39, obtained from the imides 38, took place in acetonitrile at room temperature, in an improvement on the results previously obtained for these substrates with TFA.…”