Ring opening dipolar

The ring-opened dipolar intermediate suggests reactivity towards nucleophiles and electrophiles. The latter occurs in the TiCl4 promoted addition of methyl 2-siloxycyclo-propanecarboxylates to carbonyl compounds and to an iminium salt (equation 99). The products of both processes are very versatile intermediates allowing synthesis of different furan derivatives and other compounds Concerning the liberated carbonyl function, both reactions can be classified as homoenolate additions, thus putting further emphasis on the cyclopropane homoalkene equivalence. 

When the free imine 68 is heated, the ring-opened dipolar intermediate 69 is formed The fate of this species depends on the solvent in aprotic solvents an indene derivative (70)... 

Tetramethoxyallene adds to electrophilic unsaturated systems to give [2 + 2] adducts. With tetracyanoethylene the cyclobutane (339) is obtained, which is in equilibrium with the ring-opened dipolar form (340). This accounts for the n.m.r. spectrum which shows only a singlet (t6.23) at —95°C, three methoxy signals (ratio 1 1 2) become visible. Equivalence of the four methoxy-groups in (339) is believed to be a result of the equilibrium (339) (340) and not internal rotation in the allylic cation in (340). ... 

Tetramethoxyallene and tetracyanoethylene combine to yield an equilibrium mixture of the cyclobutane (191) and the stabilized ring-opened dipolar species (192)P At —95 C the signals due to both (191) and (192) are recognizable in the n.m.r. spectrum. A similar situation is observed in the adduct from benzenesulphonyl isocyanate and tetrathioalkylallenes, the equilibrium between (193) and (194) being established. 

Reaction of thiazoles with DMAD illustrates the overall reaction and the rearrangements which may be encountered. Thiazole or 2-methylthiazole (411 R=H and Me, respectively) in DMF reacted with DMAD to give an initial 1,4-dipolar species (412). Reaction with a second DMAD gave the 1 2 molar adduct, presumably (413). Ring opening to (414), followed by cyclization in the alternative mode, resulted in the formation of (415), the structure of which (R = Me) was established by X-ray analysis (78AHC(23)263) (see also Chapter 4.19). 

The ring-opening process leading to 164 (route a) is analogous to that which has been demonstrated to follow the cycloadditions of tosyl azide to certain enamines176. Similar results have been reported for the reaction of 2,3-diphenylcyclopropenone with 2-diazopropane177. Other 1,3-dipolar cycloadditions with thiirene dioxides could also be affected (see below). 

Scheme 2.146. Synthesis of several natural products via Pummerer-type rearrangement/ 1,3-dipolar cycloaddition/ring-opening reactions.

Thermolysis of 6-substituted l,5-diazabicyclo[3.1.0]hexanes 326, easily available from 325, leads to a diaziridine ring opening and to the intermediate formation of labile azomethine imines 327. These compounds can be stabilized by a proton shift to form 1-substituted 2-pyrazolines 328. However, when the thermolysis is carried out in the presence of a 1,3-dipolarophile, the corresponding products of dipolar cycloaddition can be obtained. For example, iV-arylmaleimides provide mixtures of the major trans- and minor air-products 329 and 330, respectively (Scheme 47) C1999RJO110, 2001RJ0841, 2003RJ01338, 2004RJ067>. 

Synthetic work commenced with evaluation of an azomethine ylide dipole for the proposed intramolecular dipolar cycloaddition. A number of methods exist for the preparation of azomethine ylides, including, inter alia, transformations based on fluoride-mediated desilylation of a-silyliminium species, electrocyclic ring opening of aziridines, and tautomerization of a-amino acid ester imines [37]. In particular, the fluoride-mediated desilylation of a-silyliminium species, first reported by Vedejs in 1979 [38], is among the most widely used methods for the generation of non-stabilized azomethine ylides (Scheme 1.6). 

The 1,3-dipolar intermediate obtained in the ring opening reaction of 3H-azirines via cleavage of the C—C bond has been trapped to give oxa-zolines 355) (3.36) and pyrrolines (3.37) 356). 

Two protected 3-amino acids, containing indolizidine and quinolizidine skeletons (607a,b), have been synthesized by using 1,3-dipolar cycloaddition of nitrones (551) and (552) to methyl ( )-5-mesyloxy-2-pentenoate. The key steps of this approach is demonstrated by novel syntheses of indolizidinone and quino-lizidinone derivatives (606a,b) and by the ring opening of the tricyclic 1,3-dipolar cycloaddition products (605a,b) (Scheme 2.268) (779). 

The retro-1,3-dipolar cycloaddition of imidazo[l,5- ][l,2,4]oxadiazoles 40, promoted by reaction with triphenylphos-phine at reflux in THF, gives the cyclic nitrones 187 (unreported yields) (Equation 15) <1997T13873>. The ring opening of compounds 40 leading to heterocycles 187 (Equation 15) can also be achieved thermally in the condensed phase under vacuum <1997TL2299>. 

---