Synthesis of 5-Aryloxazolidines via 1,3-Dipolar Cycloaddition Reaction of a Non-Stabilized Azomethine Ylide with Aromatic Aldehydes

Abstract

The 1,3-dipolar cycloaddition reaction of a non-stabilized azomethine ylide 4a, formed in situ from N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine 5 and a catalytic amount of trifluoroacetic acid, with aromatic aldehydes 3 gives rise to N-benzyl-5-aryloxazolidines 1. Under these conditions, 4-hydroxybenzaldehyde 3p undergoes two-fold addition of azomethine ylide 4a to afford bis adduct 11.

1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides with Carbonyl Dipolarophiles Yielding Oxazolidine Derivatives

“…Additionally, for 4-hydroxybenzaldehyde (2t), the main product was the bis adduct 174, isolated in 53% yield (Figure 2). Recently, a thorough exploration of the reactions of reagent 178 with aromatic and heteroaromatic aldehydes 2 was reported [133]. Firstly, it was found that generating the ylide by trifluoroacetic acid catalysis [131] in CH 2 Cl 2 at 25˝C in the presence of benzaldehyde (2a) afforded a 95% yield of the oxazolidine cycloadduct 173a (Scheme 45) (Table 23, entry 1), a higher yield than that reported using LiF to generate the ylide from reagent 178 [129].…”

“…The cycloaddition of ylide 172, generated by trifluoroacetic acid catalyzed decomposition of silylamine reagent 178, to a range of heteroaromatic aldehydes 2 was also explored with the only limitation appearing to be electron-rich aromatic aldehydes (Table 24) [133]. 2-Furan-, 2-thiopheneand 3-pyridine carboxaldehydes (2u-w) all underwent efficient cycloaddition under these conditions (Entries 1-3).…”

“…Consistent with this rationale, when the pyrrole contained the electron-withdrawing N-benzenesulfonyl group (compound 2z), which was expected to lower the carbonyl LUMO energy, a high yield of the oxazolidine product 173v was obtained. The cycloaddition of ylide 172, generated by trifluoroacetic acid catalyzed decomposition of silylamine reagent 178, to a range of heteroaromatic aldehydes 2 was also explored with the only limitation appearing to be electron-rich aromatic aldehydes (Table 24) [133]. 2-Furan-, 2-thiopheneand 3-pyridine carboxaldehydes (2u-w) all underwent efficient cycloaddition under these conditions (Entries 1-3).…”

Three Ways Aliphatic Aldehydes React with Nonstabilized Azomethine Ylides

“…It has been reported that the reaction of aldehydes 1 with sarcosine and paraformaldehyde leads to N-methyl-oxazolidines 2, 6 whereas their reaction with N-(methoxymethyl)-N-[(trimethylsilyl)methyl]benzylamine in the presence of a catalytic amount of trifluoroacetic acid gives N-benzyloxazolidines 3. 7 The starting aldehydes 1 are also known to participate in the generation of azomethine ylides, forming a mixture of regioisomers 4 and 4′ (Scheme 1). 1a Scheme 1 Reactions of aromatic aldehydes with nonstabilized azomethine ylides However, to the best of our knowledge, no studies on the reactions of azomethine ylides with such central organic compounds as saturated aliphatic aldehydes have been undertaken.…”

A simple two-step synthesis of 2-(alkylamino)-1-arylethanols, including racemic adrenaline, from aromatic aldehydes via 5-aryloxazolidines

“…In this case, the benzoyl protection was removed simultaneously by demethylenation of oxazolidine 2e under the action of hydrazine hydrate (Scheme 2, Table 1). An alternative method for the generation of a nonstabilized azomethine ylide from N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine in the presence of trifluoroacetic acid, 12 followed by hydrazinolysis of oxazolidine 2j allowed us to obtain N-benzyl derivative 1j isolated as the hydrochloride. Application of this reaction to thiophene-2-carbaldehyde led to a two-step synthesis of 2-(benzylamino)-1-(thien-2-yl)ethanol (1k) in 71% yield (Scheme 3).…”