Exocyclic–Endocyclic N‐Acyliminium Ion Equilibration via an Intramolecular α‐Thioamidoalkylation in the Synthesis of Fused N,S‐Heterocyclic Systems: Some New Parameters

Abstract

The reactivity of N‐[aryl(or alkyl)thio(oxo or seleno)alkylamidals 6 bearing the N‐(CH2)n‐X‐(CH2)m‐Ar functionality towards neat TFA has been examined. Substrates of type 6 give, together with the products 11, 17, 19, and 25 of the “expected” π‐cyclization process, the “unexpected” products 12, 18, and 26 resulting from a new tandem heteroamidoalkylation/isomerization/π‐cyclization. The composition of the final isomeric mixture depends on the temperature of the reaction, with a high selectivity in favor of the “expected” π‐cyclization product 11 as a thermodynamic isomer. Furthermore, the results demonstrate again the relevance of TFA catalysis and support two reaction pathways involving the formation of an aza‐sulfonium cation A as a valuable intermediate which undergoes the π‐cyclization process alone or in tandem with the thiocyclization/isomerization to give the cyclized products cited above. For the latter tandem reaction, we have established clearly that the n value should be equal to 1, the process can be performed independently for both the succinimide and phthalimide series, the reaction depends on the nucleophilicity of the heteroatom, and can be generalized to other heterocycles. Only the role of the benzene substitution has still to be totally elucidated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Multimetallic Iridium‐Tin (Ir‐Sn3) Catalyst in N‐Acyliminium Ion Chemistry: Synthesis of 3‐Substituted Isoindolinones via Intra‐ and Intermolecular Amidoalkylation Reaction

“…The resulting white precipitate was filtered, dried and then recrystallized from ethanol to give the expected imides 2t–x in 80–90 % yields. Spectral data of the compounds 2t ,46 2v 47 and 2x 27 were in excellent agreement with those in the literature.…”

“…The combined organic extracts were dried over anhydrous sodium sulfate and evaporated to leave the hydroxylactams which were then purified by chromatography on silica gel column using a mixture of petroleum ether/ethyl acetate as eluent to furnish the lactams in 63–90% yields. Spectral data of the compounds 3a ,49 3b ,27 3c ,11c 3d ,10b 3e ,50 3q ,51 3r ,52 3s ,10b 3t ,47 3v 47 and 3x 27 were in excellent agreement with those in the literature.…”

“…Thiophenol was detected as a side product along with product 7 and this observation led us to hypothesize that a thiophenate ion which can be generated in situ by cleavage of the CH 2  S linkage under the influence of Lewis acid, attacks the iminium ion H . Daïch and co‐workers reported similar observations with the trifluoroacetic acid‐mediated reaction of N ‐arylthiomethylamidals 27. On the other hand, N ‐aryloxymethylamidals 3t–w cyclize via path c which includes oxocyclization to cyclic azaoxonium cation J , an exocyclic N ‐acyliminium ion K formation followed by arylation to product 6 .…”

Bi(OTf)3‐Catalysed Access to 2,3‐Substituted Isoindolinones and Tricyclic N,O‐Acetals by Trapping of Bis‐N‐Acyliminium Species in a Tandem Process

“…3‐Oxo‐2‐[(phenylselenyl)methyl]isoindolin‐1‐yl Acetate (8A): Acetic anhydride (0.38 mL, 4 mmol) was added dropwise to a solution of 3‐hydroxy‐2‐[(phenylselenyl)methyl]isoindolin‐1‐one ( 21 , 638 mg, 2 mmol), NEt 3 (0.56 mL, 4 mmol), and DMAP (24.4 mg, 0.2 mmol) in CH 2 Cl 2 (10 mL) at 10–15 °C with stirring. [11a] The mixture was stirred at room temperature overnight and quenched by addition of a saturated aqueous solution of NaHCO 3 .…”

“…Acetic anhydride (0.38 mL, 4 mmol) was added dropwise to a solution of 3-hydroxy-2-[(phenylselenyl)methyl]isoindolin-1-one (21, [9] 638 mg, 2 mmol), NEt 3…”