Exploring the Border between Concerted and Two-Step Pathways of 1,3-Dipolar Cycloadditions of Organic Azides to Cyclic Ketene N,X-Acetals. – Synthesis and ¹⁵N-NMR Spectra of Zwitterions and Spirocyclic Cycloadducts^†

Cyclic ketene N,X-acetals 1 are electron-rich dipolarophiles that undergo 1,3-dipolar cycloaddition reactions with organic azides 2 ranging from alkyl to strongly electron-deficient azides, e.g., picryl azide (2L; R¹=2,4,6-(NO₂)₃C₆H₂) and sulfonyl azides 2M–O (R¹=XSO₂; cf. Scheme 1). Reactions of the latter with the most-nucleophilic ketene N,N-acetals 1A provided the first examples for two-step HOMO(dipolarophile)–LUMO(1,3-dipole)-controlled 1,3-dipolar cycloadditions via intermediate zwitterions 3. To set the stage for an exploration of the frontier between concerted and two-step 1,3-dipolar cycloadditions of this type, we first describe the scope and limitations of concerted cycloadditions of 2 to 1 and delineate a number of zwitterions 3. Alkyl azides 2A–C add exclusively to ketene N,N-acetals that are derived from 1H-tetrazole (see 1A) and 1H-imidazole (see 1B,C), while almost all aryl azides yield cycloadducts 4 with the ketene N,X-acetals (X=NR, O, S) employed, except for the case of extreme steric hindrance of the 1,3-dipole (see 2E; R¹=2,4,6-(^tBu)₃C₆H₂). The most electron-deficient paradigm, 2L, affords zwitterions 16D,E in the reactions with 1A, while ketene N,O- and N,S-acetals furnish products of unstable intermediate cycloadducts. By tuning the electronic and steric demands of aryl azides to those of ketene N,N-acetals 1A, we discovered new borderlines between concerted and two-step 1,3-dipolar cycloadditions that involve similar pairs of dipoles and dipolarophiles: 4-Nitrophenyl azide (2G) and the 2,2-dimethylpropylidene dipolarophile 1A (R, R=H, ^tBu) gave a cycloadduct 13 H, while 2-nitrophenyl azide (2 H) and the same dipolarophile afforded a zwitterion 16A. Isopropylidene dipolarophile 1A (R=Me) reacted with both 2G and 2 H to afford cycloadducts 13G,J) but furnished a zwitterion 16B with 2,4-dinitrophenyl azide (2I). Likewise, 1A (R=Me) reacted with the isomeric encumbered nitrophenyl azides 2J and 2K to yield a cycloadduct 13L and a zwitterion 16C, respectively. These examples suggest that, in principle, a host of such borderlines exist which can be crossed by means of small structural variations of the reactants. Eventually, we use ¹⁵N-NMR spectroscopy for the first time to characterize spirocyclic cycloadducts 10–14 and 17 (Table 6), and zwitterions 16 (Table 7).