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

Abstract

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).

Triazenes by Acid‐Mediated Opening of the Dihydro‐1,2,3‐triazole Ring of1,3‐Dipolar Cycloadducts of Organic Azides to Cyclic Ketene N,N‐Acetals

“…[9] NMR spectra of solutions in potassium [D 2 ]dihydrogen phosphate/deuterium oxide that were obtained from 1a and d showed that protonation drastically changes the spirocyclic structures. The spiro carbon-13 signals at 100-105 ppm [9,10] are no longer observed while 1 H and 13 C NMR signals that are characteristic of 5-alkyl-1,4-dimethyltetrazolium ions make their appearance. [11] These results indicate that the dihydrotriazole ring of 1a and d was opened to yield a triazene.…”

“…The observed dynamic phenomenon is due to restricted rotation around the C(5)-CHtBu bond. In comparable zwitterions that differ from 2dX only by a triazenide side chain instead of the 3-methyltriazen-1-yl group, rotation around the C(5)-CHtBu bond is even completely frozen on the 1 H, 13 C, and 15 N NMR time scales employed, [10,18] and the tert-butyl groups adopt a conformation perpendicular below (or above) the ring planes in the solid state. [18] N-Alkyl-NЈ-phenyltriazenes prefer the 3-alkyl-1-phenyl tautomer, in which the phenyl group is conjugated with the azo group.…”

“…[9,10] Those cycloadducts 1 that have a proton attached to their triazole carbon (R 3 = H), e. g. 1d, are prone to base-induced cleavage of the dihydrotetrazole ring yielding methyl azide and 5-amino-1H-1,2,3-triazoles, which occasionally are undesired byproducts. Attempts at separation by extracting a benzene solution of a mixture containing 1d with a saturated aqueous solution of potassium dihydrogen phosphate afforded a surprising result: Not the 5-amino-1H-1,2,3-triazole as intended but 1d was extracted into the aqueous layer from which it could be recovered quantitatively after addition of concentrated sodium hydroxide solution.…”

“…IR: Perkin-Elmer 1420. The spirocycles 1a, d, [10] 1b, c, and 4 [11] were prepared according to known procedures. Tetrafluoroboric acid in diethyl ether (54 %, d = 1.19 g mL -1 ) was purchased from Merck, Darmstadt.…”

Reactions of Di(tert‐butyl)diazomethane with Acceptor‐Substituted Ethylenes

“…Such a change of mechanism has been studied for cycloadditions of thiocarbonyl ylides [9] (for a review, see [10]) and sulfonyl azides [11] [12]. A similar cooperation of steric and electronic effects is described here for cycloadditions of di(tert-butyl)diazomethane (4).…”