Methylene-277- azirines

A typical high-yield synthesis of a vinyl substituted 2/f-azirine is shown by the conversion of the azide 624 into 625". Similar behaviour is seen for the isomeric azidoeneynes 626 and 627 that are converted into the alkynyl substituted azirine 628 while irradiation of the azidoallylphosphonates 629 yields the corresponding azirines 630 and 631 is transformed into 632 at 0 This route to azirines has been extended to the synthesis of the bis-2/f-azirines 633 and 634, which are formed by irradiation of the bis azides 635 and 636", respectively. The formation of these products arises by sequential loss of nitrogen. Thus the bis azide 635 is converted to 637 prior to the ultimate formation of the final product 633. Methylene azirines such as 638 are formed on photoelimination of nitrogen from the azides 639. In this instance, however, the presence of the azirine derivative was established by trapping experiments with HCN when the adducts 640 are formed . 

The a-methylene-/3-lactam 103 is obtained by the carbonylation of the inethyleneaziridine 102 under mild conditions[91]. The azirine 104 undergoes an interesting dimerization-carbonylation to form the fused )3-lactam 105[92]. 

When the chain between the azirine ring and the alkene end is extended to three carbon atoms, the normal mode of 1,3-intramolecular dipolar cycloaddition occurs. For example, irradiation of azirine (73) gives A -pyrroline (74) in quantitative yield 77JA1871). In this case the methylene chain is sufficiently long to allow the dipole and alkenic portions to approach each other in parallel planes. 

Carbanions in the form of ylides also add to azirines. For example, treatment of 1-azirine (227) with dimethylsulfonium methylide gives 1-azabicyclobutane (229) in good yield (72JA2758). The addition of the methylene group occurs by initial nucleophilic attack by the ylide to give intermediate (228) which cyclizes with expulsion of dimethyl sulfide. 

The use of compounds with activated methylene protons (doubly activated) enables the use of a mild base during the Neber reaction to 277-azirines. Using ketoxime 4-toluenesulfonates of 3-oxocarboxylic esters 539 as starting materials and a catalytic quantity of chiral tertiary base for the reaction, moderate to high enantioselectivity (44-82% ee) was achieved (equation 240). This asymmetric conversion was observed for the three pairs of Cinchona alkaloids (Cinchonine/Cinchonidine, Quinine/Quinidine and Dihydro-quinine/Dihydroquinidine). When the pseudoenantiomers of the alkaloid bases were used, opposite enantioselectivity was observed in the reaction. This fact shows that the absolute configuration of the predominant azirine can be controlled by base selection. 

Paquette and coworkers (69JOC2866) have demonstrated that H-azepines can be forced into adopting the benzeneimine structure by bridging the 2,7-positions with a trimethylene chain (25). The length of the methylene chain is, however, critical and the tetramethylene derivative (26) exists solely as the bridged azepine. A suggestion that benzeneimines may be involved as intermediates in the formation of 3H-azepines from 2//-azirines and cyclopentadienones (Section 5.16.4.2.1(i)) has been discounted (74JOC3070). 

A palladium-catalyzed ring expansion of aziridines provided a novel route to highly substituted pyrroles <07TL2267>. Treatment of methylene aziridines 33 with Pd(0) in the presence of symmetrical 1,3-diketones 34 led to the formation of 3-ketopyrroles 35. Pyrrole-substituted nucleoside analogues were prepared using a vanadium-mediated transformation of 2-azirines in the presence of symmetrical 1,3-diketones <07SL2723>. 

Figure 6.7 The 2i7-azirine nitrile ylide conversion. The loop constructed from the azirine and the two isomeric nitrile ylides, which differ by a rotation of the methylene group by 180°, is either ip or i and encloses a conical intersection. The coordinates Qi and Qo are indicated.

Starting with y= 120° and 0 = 0°, the MNDOC-CI method yields a conical intersection, the structure of which is shown in Figure 6.8. The values 0=0° for the rotational angle and 7 = 143,7° for the bond angle are as expected the bond distances are between those of azirine and nitrile ylide, especially because the distance between nitrogen and the methylene carbon r N = 1.34 A has decreased and is equal to the double-bond value r N = 1.34 A in the nitrile ylide. To completely establish the mechanism, it remains to be shown that the conical intersection is accessible without a barrier from the Franck-Condon geometry and that the nitrile ylide can be reached from the conical intersection. This is easily... 

This reaction was first reported by Neber et al. in 1926. It is the transformation of a ketoxime 0-arylsulfonate into an Q -amino ketone involving the deprotonation of an a-methylene hydrogen by a base and the subsequent acidic hydrolysis of the resulting azirine intermediate. Therefore, this reaction is generally known as the Neber rearrangement or... 

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