Dipolar cycloreversion

In addition there are certain other methods for the preparation such compounds. Upon heating of the thionocarbonate 2 with a trivalent phosphorus compound e.g. trimethyl phosphite, a -elimination reaction takes place to yield the olefin 3. A nucleophilic addition of the phosphorus to sulfur leads to the zwitterionic species 6, which is likely to react to the phosphorus ylide 7 via cyclization and subsequent desulfurization. An alternative pathway for the formation of 7 via a 2-carbena-l,3-dioxolane 8 has been formulated. From the ylide 7 the olefin 3 is formed stereospecifically by a concerted 1,3-dipolar cycloreversion (see 1,3-dipolar cycloaddition), together with the unstable phosphorus compound 9, which decomposes into carbon dioxide and R3P. The latter is finally obtained as R3PS ... 

In 1984, a facile synthesis of pyrrolo[3,4-/7]indole (5) as a stable indole-2,3-quinodimethane analogue using an intramolecular azide-alkene cycloaddition-cycloreversion strategy was reported (Scheme 9.2) (3). Treatment of bromo compound 3 with NaNs in aqueous tetrahydrofuran (THF) produced the triazoline 4 via an intramolecular 1,3-dipolar cycloaddition of an intermediate azide. Treatment of the triazoline 4 with p-toluenesulfonic acid (p-TSA) effected 1,3-dipolar cycloreversion of 4 to give pyrroloindole 5 in 82% yield along with diethyl diazomalonate. 

This method was also applied to preparation of thieno[3,4-c]pyrroles, including the first preparation of the parent compound (Scheme 9.4) (5a,b). When treated with NaNs, the bromo compounds (12) underwent 1,3-dipolar cycloaddition to yield the triazolines 13. 1,3-Dipolar cycloreversion gave the salts of the thieno[3,4-c]pyrroles... 

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-f]pyrrole ring system 387 <2003T1477> and its derivatives was accomplished using the same synthetic sequence (Scheme 42). Starting with 2-methyl-benzo[ ]thiophene-3-carbaldehyde 388, an intermediate 389 was obtained. Treatment of bromo compound 389 with sodium azide in ethanol led to the stable triazoline 390. 1,3-Dipolar cycloreversion of 390 was induced by a catalytic amount of />-TsOH to give the parent 2//-benzo[4,5]thieno[2,3-c]pyrrole 387. Alternatively, direct treatment of bromo compound 389 with excess ammonia furnished 387 in one step. Compound 387 was treated with di-/-butyl dicarbonate and 4-dimethylaminopyridine (DMAP) to give iV-BOC derivative 391. Reaction of 389 with... 

Typical 1,3-dipolar cycloreversion is found for the decomposition of alkyl-substituted 2-tetrazolines (43) (88CB1213), l,4-dihydro-l,2,3,4-tetrazol-5-ones (44), and -thiones (45) (97JHC113). For these reactions two paths are possible that can be distinguished when the substituents on N-l and N-4 are different. For 2-tetrazolines ring contraction leading to diaziridines is also possible (discussed earlier). Cycloreversion of 43 yields imines and azides (88CB1213). 

Dipolar cycloreversion was found for several, mainly the heteroatom-rich, compounds such as pentazole (48), tetrazoles (38,46,47,48), tetrazo-lines (43), tetrazolinones (44) and -thiones (45), 1,3,4-thiadiazolines (39), 1,3,4-oxadiazolidines (42), 13,4-oxathiazolinone (40), and 1,2,3-thiadiazole (49). When the compound has an exocyclic double bond, this ring fragmentation produces two compounds with cumulated double bonds. 

Sometimes it is difficult to classify the fragmentation unequivocally, in particular when short-lived, reactive intermediates that readily decompose into smaller fragments may or may not be encountered depending on reaction conditions. As examples, the oxadiazolines (20,75) can be mentioned (see Sections V.A and VI). Many reactions classified as [5 - 2 + 2 + 1] fragmentations (Section VI) are probably initiated as a [5 —> 3 + 2] 1,3-dipolar cycloreversion. 

Dipolar cycloadditions are another important family, with the impressive sequence of reactions involved when ozone reacts with an alkene as an example here. At -78°, ozone adds 1.3 (arrows) to give the molozonide 1.4. On warming, this undergoes a 1,3-dipolar cycloreversion (1.4 arrows),... 

The Criegee mechanism for ozonolysis a dramatic sequence with successively a 1,3-dipolar cycloaddition, a 1,3-dipolar cycloreversion and another 1,3-dipolar cycloaddition, all taking place below room temperature. 

Thione-.Y-ylidcs 219 are unstable compounds which are formed in situ from the thermally labile 1,3,4-thiadiazo-lines 218, via a 1,3-dipolar cycloreversion process liberating nitrogen. They react with the N=S bond of Ar-sul linylamincs 220, affording the 1,4,2-di thiazolidinc-.Y-oxidc derivatives 221 (Scheme 30) <1999HAC662>. 

Dimethyl acetylenedicarboxylate (DMAD) is able to trap both products of the reversible thermal 1,3-dipolar cycloreversion. With an excess of DMAD at 60 °C without solvent, the product 247 (Ar = Ph) arising from thiosulfine was formed in 83% yield, and the benzothiopyran 248 arising from the thiobenzophenone in 68% yield. With R = C1, yields were slightly lower (Scheme 77) <1997T939>. 

Dipolar Cycloadditions and 1,3-Dipolar Cycloreversions as Steps in the Ozonolysis of Alkenes... 

The presence of two O—O bonds renders primary ozonides so unstable that they decompose immediately (Figures 15.47 and 15.48). The decomposition of the permethylated symmetric primary ozonide shown in Figure 15.47 yields acetone and a carbonyl oxide in a one-step reaction. The carbonyl oxide represents a 1,3-dipole of the allyl anion type (Table 15.2). When acetone is viewed as a dipolarophile, then the decomposition of the primary ozonide into acetone and a carbonyl oxide is recognized as the reversion of a 1,3-cycloaddition. Such a reaction is referred to as a 1,3-dipolar cycloreversion. 

The chemistry of primary ozonides is more varied if they are less highly alkylated than the primary ozonide of Figure 15.47. This is particularly true if the primary ozonide is unsym-metrical, like the one shown in Figure 15.48. This is because its decay may involve two different 1,3-dipolar cycloreversions. Both of them result in one carbonyl oxide and one carbonyl compound. If the reaction is carried out in methanol, the two carbonyl oxides can react with the solvent (as in Figure 15.47) whereby each of them affords a hydroperoxide (an ether peroxide analog). 

Phenyl azide is formed from phenyldiazonium chloride and sodium azide by way of two competing reactions (Figure 12.46). The reaction path to the right begins with a 1,3-dipolar cycloaddition. At low temperature, this cycloaddition affords phenylpentazole, which decays above 0°C via a 1,3-dipolar cycloreversion. This cycloreversion produces the 1,3-dipole phenyl azide as the desired product, and molecular nitrogen as a side product. 

Lactones of azocarboxylic acids are remarkably reactive. In the presence of phenyl isocyanate, the imino isocyanate formed from reactive 2-hydrazono-A3-l,3,4-oxadiazolines via a 1,3-dipolar cycloreversion is intercepted to give [l,2,4]triazolo[l,2-a]-[l,2,4]triazole-l,3,5-triones by means of two subsequent [2 + 3] cycloadditions via azomethine imine intermediates (Scheme 10) (76T2685). 

The mass spectrometry of 1,2,4-oxadiazoles is dominated by stepwise 1,3-dipolar cycloreversion, i.e., fragmentation 191. This fragmentation is particularly useful for 1,2,4-oxadiazole characterization and a wide selection of derivatives undergo cleavage to a nitrile oxide fragment <2003H(60)2287, CHEC-III(5.04.3.3)249>. Mass spectrometric analysis of 1,2,4-oxadiazoles and dihydro-1,2,4-oxadiazoles has been reviewed <2005MI328>. 

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