Alkenes azomethine ylide, intramolecular cycloadditions

Scheme 6.186 Intramolecular azomethine ylide-alkene/alkyne [3+2] cycloadditions.

The addition to alkenes normally leads to unstable adducts that lose carbon dioxide under the reaction conditions. The intramolecular cycloaddition of the sydnone (30) takes place at room temperature, however (Equation (5)) and the cycloadduct (31) has been characterized <86HCA927>. The unstable species formed by the loss of carbon dioxide are also azomethine ylides. It is therefore possible for a second 1,3-dipolar addition to take place, as illustrated in Scheme 6 for the reaction of 3-phenylsydnone with Al-phenylmaleimide <86TL317,92JA8414>. This 2 1 addition has been used as the basis of a synthesis of polyimides. Imides of the type (32) were used as the dipolarophiles and their reaction with 3-phenylsydnone gave linear polymers <87MM726>. 

Harwood and Lilley (87) reported the tandem generation and intramolecular trapping of a stabilized azomethine ylide, derived from the enantiopure template examined in detail in Section 3.2.3. Condensation of 5-hexenal with template 205 under standard conditions led to in situ ylide generation and subsequent cycloaddition of the tethered alkene to furnish 296 as a single enantiomer in 95% yield after purification and this despite the fact that the dipolarophile is unactivated. Hydro-genolytic destruction of the template revealed the bicyclic amino acid 297 in 75% yield (Scheme 3.97). 

UV Irradiation of an 3-aryl-2-azidoacrylic ester (2-azidocinnamate) results in elimination of nitrogen and formation of a 2/f-azirine, which undergoes spontaneous electrocyclic ring opening to give a reactive intermediate which can react as an azomethine ylide dipole or an alk-oxycarbonyl(benzylidenimino)carbene. In favorable cases, the carbene form can be trapped by intramolecular [l-t-2] cycloaddition to an alkene double bond to give a dihydro-cyclopropa[c]isoquinoline, e.g.l, and 2 (Houben-Weyl, Vol. E19b, pi 166). 

An intramolecular allyl silane/N-sulfonyl iminium ion cyclization has also been used as a pivotal step in an approach to the tricyclic core of the unique marine alkaloid sarain A [46]. The starting material was aziridine ester 129 (Scheme 25) which was elaborated to amide 130. An important step in the synthetic strategy was thermolysis of 130 to an azomethine ylide, which underwent stereospecific intramolecular 1,3-dipolar cycloaddition with the Z-alkene to produce bicyclic lactam 131 [47]. This compound was then elaborated into allyl silane 132. It was then possible to replace the lactam N-benzyl functionality with a tosyl moiety, leading to 133, and subsequent reduction of the carbonyl group afforded the desired cyclization precursor a-hydroxy sulfonamide 134. Exposure of 134 to ferric chloride promoted cyclization to a single stereoisomeric tricyclic amino alkene 136 having the requisite sarain A nucleus. It is believed that the intermediate N-sulfonyl iminium ion cyclizes via the conformation shown in 135. 

Some examples of exojendo diastereoselection in intramolecular azomethine ylide cycloadditions are known215, 262,279 29where the azomethine ylide is generated by differing procedures. The intramolecular nature of the process allows the reaction to occur on unactivated alkenes that generally are too sluggish to react in an intermolecular way215,286. 

Condensation of the aldehyde 9 and A-methyl-glycine gives an intermediate imininum ion which is trapped intramolecularly to give an oxazolidinone. Thermal elimination of CO2 generates an azomethine ylide that undergoes ready intramolecular dipolar cycloaddition onto the alkene. The di-flised product will have the lower activation energy. See C. J. Lovely and H. Mahmud, Tetrahedron Lett., 40 (1999), 2079. 

Cycloaddition reactions also provide a very straightforward means for the preparation of the quinoline scaffold. Hexahydropyrrolo[3,2-c]quinolines, the core structure of the Martinella alkaloids, were prepared through an intramolecular 3 + 2] azomethine ylide-alkene cycloaddition. Condensation of an aldehyde such as 51 and W-alkyl amino acids followed by decarboxylation and cycloaddition afforded quinoline derivatives such as 52 <01T4095>. The... 

A related method was applied to the synthesis of 18 isoxazolothiohydantoins (Scheme 11.51)/ Hydantoin formation was also applied to the release of proline derivatives that were obtained from the intramolecular cycloadditions of resin-bound azomethine ylides and alkenes. ... 

Cycloaddition of azomethine ylides (94) with alkenes provides adducts that can be desulphurized to give pyrrolidines (95), and AT-allyldiazoacetamides, which are unstable at 20 C, undergo intramolecular 1,3-dipolar cycloaddition to give c/s-hexahydropy rrolo[3,4-c]pyrazoles (97). It was found that the amide derivatives (96, R = COaEt) react faster but that the isostere (98) fails to react. 

A versatile and flexible method of pyrrohdine synthesis is the 1,3-dipolar cycloaddition of azomethine ylides 1 to activated alkenes, which is realized in many inter- and intramolecular examples [228] ... 

Scheme 4.20 Synthesis of fused tricyclic amine by intramolecular 1,3-dipolar azomethine ylide-alkene cycloaddition.

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