Acid-Promoted Oxygen-Atom Transfer from a Novel Dihydroisoquinoline-Derived Oxaziridine Substituted at Position 1

Abstract

N-Alkyl-oxaziridines react in the presence of a nucleophile as an oxygenating agent; in the absence of a nucleophile, an isomerization reaction is observed. This study describes the synthesis of two new dihydroisoquinoline oxaziridines and their reactivity in an acid-promoted reaction in the presence and absence of sulfides.

Synthesis and reactivity of new dihydroisoquinoline-derived oxaziridines

“…We have focused on the structural modification of the oxaziridines, most notably the substitution at position 1, that can lead to useful reagents for the electrophilic oxidation of wide variety of nucleophiles. 31 In an acidic medium and in the absence of nucleophiles, the oxaziridine can be subject to a competitive transformation which, through O-protonation, isomerize to a nitrone. In the presence of nucleophiles, the oxaziridine can be an oxygen transfer agent to organo-sulfides, as has previously been reported.…”

“…The dihydroisoquinoline oxaziridines have previously been reported to be promising agents for the transfer of oxygen to organosulfides in the presence and absence of acid. [30][31][32][33] The substitution at position 1 onto the dihydroisoquinoline skeleton has a marked influence in the formation of sulfoxide or nitrone products from the oxidation reactions of the oxaziridines. 31,33 We have noted a significant variation in reaction times when we changed the structure of oxaziridine, most notably the substitution at position 1.…”

“…[30][31][32][33] The substitution at position 1 onto the dihydroisoquinoline skeleton has a marked influence in the formation of sulfoxide or nitrone products from the oxidation reactions of the oxaziridines. 31,33 We have noted a significant variation in reaction times when we changed the structure of oxaziridine, most notably the substitution at position 1. Indeed, the unsubstituted dihydroisoquinoline oxaziridine can oxidize quickly the p-tolylmethyl sulfide to the sulfoxide, 32 whereas oxygen transfer is slowest in the presence of steric hindrance, in position 1, of the oxaziridine.…”

“…Indeed, the unsubstituted dihydroisoquinoline oxaziridine can oxidize quickly the p-tolylmethyl sulfide to the sulfoxide, 32 whereas oxygen transfer is slowest in the presence of steric hindrance, in position 1, of the oxaziridine. 31 As part of our interest in the reactivity of oxaziridines and particularly in the design of a dihydroisoquinoline-derived family which is able to react in an oxygen transfer process, the present study aimed to synthesize new oxaziridines, namely 6-9. We also examine the effect of the introduction of a p-chlorophenyl group substituted in position 1 and of two nitro groups, one in the phenyl ring and one in the isoquinoline skeleton, on the reaction of oxygen transfer to sulfides forming sulfoxides in an acid promoted reaction.…”

Synthesis of 3,4-dihydroisoquinoline N-oxides via palladium-catalyzed intramolecular cyclization of 2-alkylbenzaldoximes

“…However, the use of extra oxidants, complicated or noble metal catalysts, toxic additives, greater toxicity organic solvents and/or prolonged reaction times were usually needed in these processes. There were two other strategies to synthetize 3,4-dihydroisouinolines N-oxides: the isomerization of oxaziridines 16 and the cyclization reactions of nitrogen compounds. [17][18][19] Similarly, these two methods had obvious drawbacks.…”