Dienes azide 1,3-dipolar cycloadditions

Vogel and Delavier (26) reported a synthesis of the 6-azabicyclo[3.2.2]nonane skeleton 130 using an intramolecular azide-alkene cycloaddition strategy (Scheme 9.26). When refluxed in xylene, the azide 126 underwent an intramolecular 1,3-dipolar cycloaddition with the internal alkene. Nitrogen extrusion and subsequent rearrangement led to a mixmre of compounds 128, 129, and 130. Reactions of azides with the double bond of dienes were also used in various total syntheses of alkaloids, and will be discussed later in Section 9.2.2. 

Hudlicky et al. (65) reported a formal stereoselective total synthesis of the oxygenated pyrrolizidine alkaloids platynecine (336), dihydroxyheliotridane (337), hastanecine (341), and tumeforcidine (342), involving an intramolecular azide-diene cycloadditions (Scheme 9.65). Intramolecular 1,3-dipolar cycloaddition of... 

Pearson et al. (68) reported a versatile approach to pyrrolizidine and indolizidine alkaloids such as 355, 247, and 362 using intramolecular cycloadditions of azides with electron-rich dienes (Scheme 9.68). Azido dienes 353, 357, and 360 that possess a electron-donating group on the diene were prepared from the respective compounds 352, 356, and 359. On heating at 100 °C, the azido diene 353 underwent smooth intramolecular 1,3-dipolar cycloaddition in a stereoselective... 

Fig. 2.3 shows the core structures of the most important 1,3-dipoles, and what they are all called. As with dienes, they can have electron-donating or withdrawing substituents attached at any of the atoms with a hydrogen atom in the core structure, and these modify the reactivity and selectivity that the dipoles show for different dipolarophiles. Some of the dipoles are stable compounds like ozone and diazomethane, or, suitably substituted, like azides, nitrones, and nitrile oxides. Others, like the ylids, imines, and carbonyl oxides, are reactive intermediates that have to be made in situ. Fig. 2.4 shows some examples of some common 1,3-dipolar cycloadditions, and Fig. 2.5 illustrates two of the many ways in which unstable dipoles can be prepared. 

The intermolecular 1,3-dipolar cycloaddition of aryl azides with 1,3-dienes produced vinyldihy-drotriazoles67, which were successively transformed photochemically to vinylaziridines42. Ring opening of these aziridines with the iodide ion, followed by ring closure afforded 2,5-di-hydropyrroles141. 

Blackwell, G.B. Haszeldine, R.N. Taylor, D.R. Polyhalogeno-allenes and -acetylenes. Part 15. Dipolar cycloadditions of V-phenylsydnone and aryl azides to perfluoropropa-diene and perfluoropropyne. J. Chem. Soc., Perkin Trans. 1 1982, 2207-2210. 

Many classes of alkaloids reveal a pyrrolizidine skeleton as a key structural element. Hudlicky et al. and Pearson et al. demonstrated the applicability of 1,3-dipolar cycloaddition of an azide with an alkene moiety in a conjugated diene to generate pyrrolizidines [38-42]. The triazoline 73 was formed by an... 

Intramolecular 1,3-dipolar cycloadditions of azides have also been investigated as a route to the pyrrolizidine ring system. For example, ethyl 8-azidoocta-2,4-dienoate (56) was converted in high yield into the labile vinylaziildine 57 when it was heated under reflux in toluene. In other experiments it was demonstrated that activation of one of the double bonds of the diene was essential in order to achieve efficient intramolecular cycloaddition. The vinylaziridine 57 was then converted into the pyrrolizidine 58 by flash pyrolysis followed by catalytic hydrogenation of the product (Scheme 6.26). 

Scheme 4.19 1,3-Dipolar cycloaddition reactions of organic azides with morpholinobuta-1,3-dienes.

Reactions.—Thioketen (83) reacts with azomethines to give /ff-thiolactams. It has been suggested that the dipolar species (84) is formed, instead of the classical dipolar species (85), in the rate-determining step of the cycloaddition. Bis-(trifluoromethyl)thioketen (86) adds to azomethines, isothiocyanates, and azides to form 1,3,5-dithiazines and thiazetidines, 1,3-dithietans, and A -1,2,3,4-thia-triazolines, respectively. The thioketen (86) also undergoes [4 + 2]cycloadditions with dienes. ... 

Cycloadditions. Methyl and ethyl cyanoformate have been reported to undergo [4 + 2] cycloadditions, e.g. with cyclopentadienones and 2-alkyl-l-ethoxybuta-1,3-dienes to form pyridines (eq 21), and with cyclobutadienes to form Dewar pyridines (eq 22). Ethyl cyanoformate is also ein effeetive dipolarophile, undergoing 1,3-dipolar addition to azides (eq 23) and cyclic carbonyl ylides (eq 24). ... 

---