Aziridine azomethine ylides from

The thermolytic preparation by De Shong et al. (74) of azomethine ylides from aziridines and their intermolecular reactions are the first examples of singly stabilized ylides of this type. However, the protocol has been further extended to include intramolecular processes. Aziridines tethered to both activated and unactivated alkenes were subjected to flash vacuum thermolysis generating cycloadducts in moderate-to-excellent yields. While previously singly activated alkenes had furnished low material yields via an intermolecular process, the intramolecular analogue represents a major improvement. Typically, treatment of 222 under standard conditions led to the formation of 223 in 80% yield as a single cis isomer. Similarly, the cis precursor furnished adduct 224 in 52% yield, although as a 1 1 diastereomeric mixture (Scheme 3.77). 

Triazolines bearing three electron-withdrawing groups (Scheme 85) undergo complex thermolysis reactions. Aziridine formation is observed but sometimes the azide cycloreversion operates pyrrolidines are thus formed by reaction of the olefins with the azomethine ylides from the aziridines. The aziridines also dimerize to piperazines under the conditions of thermolysis.446... 

Azomethine ylides are also frequently obtained by ring opening of aziridines, and the analogous carbonyl ylides from oxiranes. These aspects are dealt with in Section 3.03.5.1. A variety of five-membered heterocycles can also function as masked 1,3-dipoles and this aspect is considered in Section 3.03.5.2. 

Azomethine ylides (Section 4.03.6.1.1) have been generated from a wide variety of aziridines using both thermal and photochemical methods. With carbon-carbon unsaturated dipolarophiles, pyrrolines or pyrrolidines are obtained. With hetero double bonds, however, ring systems of interest to this discussion result. 

In some cases 0-substituted oximes reacted with azomethine ylides. Thus, reaction of 0-substituted oxime (NC)2C=NOTs 139 with azomethine yhde derived from aziridine 140 afforded imidazoline 141 in 44% yield (equation 61). Addition of lithium derivative of silylated alkyne to oxime ethers 142 leads to 4-ethynyl-Af-hydroxy-2-imidazolines 143 in 49-72% yields (equation 62) . 

In synthetic efforts toward the DNA reactive alkaloid naphthyridinomycin (164), Gamer and Ho (41) reported a series of studies into the constmction of the diazobicyclo[3.2.1]octane section. Constmction of the five-membered ring, by the photolytic conversion of an aziridine to an azomethine ylide and subsequent alkene 1,3-dipolar cycloaddition, was deemed the best synthetic tactic. Initial studies with menthol- and isonorborneol- tethered chiral dipolarophiles gave no facial selectivity in the adducts formed (42). However, utilizing Oppolzer s sultam as the chiral controlling unit led to a dramatic improvement. Treatment of ylide precursor 165 with the chiral dipolarophile 166 under photochemical conditions led to formation of the desired cycloadducts (Scheme 3.47). The reaction proceeded with an exo/endo ratio of only 2.4 1 however, the facial selectivity was good at >25 1 in favor of the desired re products. The products derived from si attack of the ylide... 

The chiral dipolarophiles of Garners and Dogan, which were derived from Oppolzer s sultam, have been previously discussed in Section 3.2.1 and, in an extension to these results, the sultam moiety was used as the stereodirecting unit in enantiopure azomethine ylides (56). The ylides were generated either by thermo-lytic opening of N-substituted aziridines or by the condensation of the amine functionality with benzaldehyde followed by tautomerism. These precursors were derived from the known (+)-A-propenoylbornane-2,10-sultam. Subsequent trapping of the ylides with A-phenylmaleimide furnished the cycloaddition products shown in Schemes 3.60 and 3.61. 

In a similar approach, Garner et al. (78) made use of silicon-based tethers between ylide and dipolarophile during their program of research into the application of azomethine ylides in the total asymmetric synthesis of complex natural products. In order to form advanced synthetic intermediates of type 248 during the asymmetric synthesis of bioxalomycins (249), an intramolecular azomethine ylide reaction from aziridine ylide precursors was deemed the best strategy (Scheme 3.84). Under photochemically induced ylide formation and subsequent cycloaddition, the desired endo-re products 250 were formed exclusively. However, due to unacceptably low synthetic yields, this approach was abandoned in favor of a longer tether (Scheme 3.85). 

Chiral aziridines having the chiral moiety attached to the nitrogen atom have also been applied for diastereoselective formation of optically active pyrrolidine derivatives. In the first example, aziridines were used as precursors for azomethine ylides (90-95). Photolysis of the aziridine 57 produced the azomethine ylide 58, which was found to add smoothly to methyl acrylate (Scheme 12.20) (91,93-95). The 1,3-dipolar cycloaddition proceeded with little or no de, but this was not surprising, as the chiral center in 58 is somewhat remote from the reacting centers... 

Garner et al. (90,320) used aziridines substituted with Oppolzer s sultam as azomethine ylide precursors. The azomethine ylide generated from 206 added to various electron-dehcient alkenes, such as dimethyl maleate, A-phenylmalei-mide, and methyl acrylate, giving the 1,3-dipolar cycloaddition product in good yields and up to 82% de (for A-phenylmaleimide). They also used familiar azomethine ylides formed by imine tautomerization (320). Aziridines such as 207 have also been used as precursors for the chiral azomethine ylides, but in reactions with vinylene carbonates, relatively low de values were obtained (Scheme 12.59) (92). 

Azomethine ylides can be generated from oxazolidines in the liquid phase by thermolysis and in the gas phase by FVP (90TL6017 92T8947). Depending on the other substituents and the FVP conditions, from 2-isopropyloxazolidines (41) either aziridines or enamines, or a mixture of them, are obtained by ring closure or hydrogen shift of the azomethine ylide. 

Unactivated dipolarophiles readily participate in intramolecular azomethine ylide cycloadditions with a more reactive azomethine ylide. Thus, flash vacuum pyrolysis of aziridine (113) afforded a 67% yield of the 5,5-fused bicyclic pyrrolidine (Scheme 34).59 A singly stabilized azomethine ylide was the apparent intermediate. Similarly, cyclization of the azomethine ylides derived from (114a-c) gave the corresponding cw-fused 6,6-bicyclic pyrrolidines in 69%, 26% and 16% yield, respectively the original double bond stereochemistry was retained in the latter two cases. 

The presence of an aroyl fragment in azomethine ylides obtained from opening of three-membered rings in the case of dipolarophiles with high LUMO (lowest unoccupied molecular orbital) energy or in the absence of an external dipolarophile can lead to the possibility of such unusual reactions as intramolecular 1,3-dipolar cycloaddition [80]. Examples of such reactions are the thermal isomerization of aroyl aziridines 63 into a pyrrole derivative 64 [81, 82] or into 2,5-diphenyloxazole 65 (in the presence of diphenyliodonium iodide) [83] (Scheme 1.16). 

Compound 46 and benzaldehyde are considered to be most likely formed by the ring-opening reaction of aziridine 44, giving an azomethine ylide, followed by hydrolysis. Thermolysis of 32 also affords 44-46, and benzaldehyde in 79%, 100%, 15%, and 16% NMR yield, respectively. This is the first example of aziridine formation from heterocyclobutanes with high coordinate main-group elements. 

Although trifluoropropene reacts poorly with the stabilized azomethine ylide generated by thermal ring opening of an aziridine, trifluoromcthyl-substituted alkenes are excellent dipolarophiles with azomethine ylides generated from organosilylated compounds, or with melalloazomethine ylides. 

When reacted with 1-aryl-3,3,3-trifluoropropynes, azomethine ylide 14, generated from the aziridine, provides pyrrolines in high yield, with no rcgioseleclivily. These cycloadducts can be converted into the corresponding pyrroles or pyrrolidines. ... 

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