Structure of a spiro-fused , 2 , 2-dioxy-∆ 3-1 , 3 , 4-oxadiazoline

3,4-Diaza-2,2,8,8-tetramethyl-1,6,10-trioxaspiro[4.5]dec-3-ene (6) was synthesized. The single crystal X-ray structure shows that the 6-membered ring is in the chair conformation with the azo group in the axial position. Comparison of the C NMR spectra of 6 in solution and in the solid state indicates that the preferred conformation in solution is also that with the azo group axial. Thus, although an alkoxy group normally occupies the axial position (the anomeric effect), the azo group outranks it insofar as the axial preference is concerned. Thermolysis of 6 in benzene afforded N2, acetone, the carbene dimer 2-(5',5'-dimethyl-1,3dioxan-2-ylidene)-5,5-dimethyl-1,3-dioxane, and 2-hydroxy-5,5-dimethyl-1,3-dioxane from reaction of the carbene intermediate with adventitious water. Those products were taken as evidence for the intermediacy of the carbene, 5,5-dimethyl-1,3-dioxan-2-ylidene.


Introduction
Dialkoxycarbenes are nucleophilic carbonyl group equivalents.They have been generated primarily in the four ways illustrated with Scheme 1. Thermolysis of 7,7dialkoxynorbornadienes 1 in solution at about 140 o C causes cheletropic cycloreversion to a dialkoxycarbene and an arene but the process involves side reactions that may interfere with the isolation of carbene-derived products.Moreover, the synthesis of 7,7-dialkoxynorbornadienes with different alkoxy groups is not simple because the cyclopentadienone acetal precursor is usually prepared from hexachlorocyclopentadiene and an alcohol. 2 Photolysis of dialkoxy diazirines is an excellent method for generating dioxycarbenes for spectroscopic studies and for mechanistic work 3 but such diazirines must generally be used as dilute solutions as neat diazirines are explosive.Orthoformates have been used effectively at 140 o C as dialkoxycarbene precursors 4 , but they are not suitable as sources of unsymmetric dialkoxycarbenes.2,2-Dialkoxy-5,5-dimethyl-∆ 3 -1,3,4-oxadiazolines have a number of advantages.They are shelf stable in pure form but at 100-110 o C they afford primarily a dialkoxycarbene, N 2 , and acetone, Scheme 2. 5 Moreover, symmetrically-and unsymmetrically-substituted 2,2-dialkoxy-5,5-dialkyl-∆ 3 -1,3,4oxadiazolines can be prepared readily, as well as 2-alkoxy-2-aryloxy-and 2,2-diaryloxy oxadiazolines, by the exchange method.5b, 6 Given the utility of 2,2-dialkoxy-∆ 3 -1,3,4-oxadiazolines as thermal precursors of dialkoxycarbenes, it was of interest to synthesize some spirocyclic analogues to investigate their structures.In this paper, we report the structure of an oxadiazoline, spiro-fused through C-2 to a six-membered ring.The system investigated (6) could have either a preference for the azo-axial conformation (6a) or the alkoxy-axial conformation (6b), Scheme 3.According to many studies of the anomeric effect 7 , alkoxy substitutents have a preference for the axial position when the competition is with an alkyl group or with H.Although the source of the anomeric effect has been the subject of debate, it is clear that the more electron-withdrawing substituent, in systems that are sterically unbiased (eq [1]) adopts the axial position. 8Based on that precedent, one would predict that the azo group (sigma p-phenylazo= 0.33) 9 would outrank an alkoxy group in terms of axial preference, in a system such as 6, eq [2].
Condensation of 3 with acetone gave 4, and oxidation 5b of 4 with lead tetraacetate (LTA) in dichloromethane afforded a mixture containing 5. Cyclization of 5 to 6 was accomplished with trifluoroacetic acid in dichloromethane, Scheme 3. The structure of 6 in the solid state was determined by means of single crystal X-ray diffraction.A gross feature of the structure is the chair-like geometry of the 6-membered ring and the axial position of the azo group of the 5membered ring, Table 1.That geometry might reflect an inherent preference for the "azo axial" conformation in the solution from which the oxadiazoline had crystallized or it could be caused by lattice forces in the solid.In order to distinguish between the two possibilities, the 13 C NMR spectrum of solid 6 was acquired for comparison with the spectrum of 6 in solution.In that way it was possible to link the known structure in the solid state (X-ray), via the 13 C spectra of both the solid and the solution, to the probable conformation of 6 in solution.
Table 2 lists the solid-state and the solution-phase 13 C NMR spectra of 6 as well as the 1 H NMR spectrum of 6 in solution. .All signals in the spectrum of the solid were relatively sharp except those from C2 and C5, which are broadened by quadrupolar coupling to the azo nitrogens.
Comparison of the 13 C data shows that the 13 C chemical shifts in the solid are very similar to those of 6 in chloroform solution; the average difference is only 0.6 δ.This result suggests that the conformations in the solid state and in solution are the same.
Although the axial azo bond (N4-C5) appears at first glance to be longer than the other azo bond (C2-N3), just as the axial C-aryl bonds of the system in Eq. [1] were longer than the equatorial C-aryl bonds, 8 the uncertainties mean that the difference is not significant.
Reactions of 6 -Thermolysis of 6 in benzene-d 6 at 100 o C was followed by 1 H NMR spectroscopy, with toluene as internal standard for integration.Depletion of 6 followed the first order rate law; k = 1.19 x 10 -5 s -1 at 100 ºC, from 15 data points to 88 % of completion.

Thermolysis of 6.
A solution of 6 (318 mg.11.6 mmol) in benzene (15 mL) was degassed by means of three freeze/pump/thaw cycles and the tube was sealed.The tube was heated at 110 ºC for 72 h.
Cumene (17 µL.0.12 mmol) was added as internal standard and yields were estimated from the GC trace.