Trifluoroacetic acid-catalyzed 1,3-cycloaddition of the simplest iminium ylide leading to 3- or 3,4-substituted pyrrolidines and 2,5-dihydropyrroles.

1,3-Dipolar cycloaddition reactions of azomethine ylides with aromatic dipolarophiles

“…69,70 Thus, Nbenzylazomethine ylide 49b can be formed in situ from reaction of N-methoxymethyl-(Ntrimethylsilylmethyl)benzylamine 56 and a catalytic amount of trifluoroacetic acid at 0 °C to room temperature (Scheme 14). [71][72][73] Consistent with the earlier work of Gribble, 68 2-nitro-1-tosylindole 57 underwent efficient cycloaddition reaction to afford the tricyclic product 58 in excellent yield (Scheme 15). 70 Additionally a series of 3-substituted indoles 59 underwent cycloaddition reactions with the azomethine ylide under these conditions (Scheme 16, Table 1).…”

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

“…When 178 was reacted in this way with ketones, benzophenone (3c) or acetone (3d), moderate yields of the corresponding cycloadducts 179 or 180 were obtained (Scheme 44). By far the most studied and utilized of the α-substituted methyl(trimethylsilylmethyl)amine reagents is the N-methoxymethyl-substituted reagent 178 [129][130][131], readily produced from benzylamine by alkylation with chloromethyltrimethylsilane followed by reaction with formaldehyde in the presence of methanol [132]. The reagent is now commercially available from various vendors.…”

“…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 trifluoroacetic acid catalysis method was then applied to a range of aromatic aldehydes 2 (Table 23).…”

Synthesis of 3-substituted pyrrolidines

“…The use of such olefins in the this reaction with various types of catalyst (F -, protic acids, Lewis acids) has been described. However, no systematic investigations into the effect of the nature of the catalyst and the reaction conditions on the course of the process have been described in the literature [2,3].In addition, the use of the costly and unstable N-benzyl-N-(methoxymethyl)-N-(trimethylsilylmethyl)amine (1) as starting compound prevented the widespread application of such a method for the construction of the pyrrolidine ring. For this reason we decided, first of all, to optimize the method for the preparation of the amine 1.…”

“…The use of such olefins in the this reaction with various types of catalyst (F -, protic acids, Lewis acids) has been described. However, no systematic investigations into the effect of the nature of the catalyst and the reaction conditions on the course of the process have been described in the literature [2,3].…”