Aziridines azomethine ylide generation

Pyrrolidine derivatives such as 206 have been synthesized by the addition of the corresponding azomethine ylide generated by the thermal ring opening of the aziridine 205 (or similar aziridines) as shown in Scheme 4.33 [204, 210-212],... 

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). 

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. 

With trifluoroniethyl-substituted azomethine ylides, generated in situ by the ring opening of fM-2-benzoyl-l-methyl-3-(trifluoromethyl)aziridine or by protonation of trifluoro-... 

With trifluoromethyl-substituted azomethine ylides, generated in situ by the ring opening of CAV-2-bcnzoyl-l -methyl-3-(trifluoromcthyl)aziridine (2)124 or by protonation of trifluoro-methylated thioamidinium salts, 25 1,3-dipolar cycloadditions with both electron-deficient and electron-rich alkenes can be achieved rcgiosclcctively. However, stereoselectivity depends on both the ylide configuration and electronic interactions. 

Azomethine Ylides. Various azomethine ylides, generated by different methods, can be trapped by 1 to give spirocyclic 1,3-thiazolidines. Thermolysis of cis aziridines of type 37 in the presence of 1 occurs stereoselectively to give frans configured cycloadducts (38) (eq 16). Reactions carried out with trans-aziridines lead to as-substituted 1,3-thiazolidines. 

The azomethine ylides, generated from aziridines 1, xmderwent 1,3-dipolar cycloaddition wiffi dimethyl acetyl-enedicarboxylate in supercritical CO2 (Scheme 1) [17]. Under photolysis conditions, dihydropyrrole 2 was formed with 43% yield. It was foxmd that using small quantity of acetonitrile as a cosolvent improved the yield to 63%. The photolysis of similar aziridine (1, = Bn, = Ph) was not efficient and the thermolysis was used to generate a reac-... 

The similar [3 + 2] cycloaddition of benzyl allenoates with azomethine ylides, generated from aziridines 1, was accompanied by a retro-aldol-type fragmentation with elimination of benzaldehyde and therefore leading to ffie... 

P.J.S. Gomes, C.M. Nimes, A.A.C.C. Pais, T.M.V.D. Pinho e Melo, L.G. Arnaut, 1,3-EHpolar cycloaddition of azomethine ylides generated from aziridines in supercritical carbon dioxide. Tetrahedron Lett. 47 (2006) 5475-5479. 

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. 

Aziridines, e.g. (91), undergo thermal ring opening in a conrotatory manner to generate azomethine ylides. These azomethine ylides are 47r-components and can participate in [4 + 2] cycloadditions with 1-azirines acting as the 27r-component 73HCA1351). 

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). 

In the examples presented in CHEC-II(1996) in which a pyridazin-3(2//)-one is the 1,3-dipolarophile, two types of 1,3-dipoles are used nitrile oxides and diazoalkanes. Two other 1,3-dipoles have to be mentioned now. The 1,3-dipolar cycloaddition of the azomethine ylide 95 generated in situ by thermal ring opening of dimethyl trans- -(A-methoxyphenyl)aziridine-2,3-dicarboxylate 94 to some 4- or 5-substituted 2-methylpyridazin-3(2//)-ones has been... 

As previously described, thermolysis of aziridines is one of the standard methods for the generation of azomethine ylides. A diastereomeric mixture of the aziridines 199 possessing an enantiomerically pure N-substituent underwent ylide formation at 280 °C and subsequent cycloaddition to vinylidine carbonate to form a mixture of four separable compounds (d-200, l-201, d-202, l-203) in a 3 3 1 1 ratio (55). Subsequent LiAlH4 reduction and hydrogenolytic N-benzyl cleavage led to all... 

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. 

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). 

During the synthetic efforts of Heathcock and co-workers toward the complex marine alkaloid sarain-A (Scheme 3.80), he outlined an elegant intramolecular, azomethine ylide cycloaddition, as one of the key stages in the construction of the central core (76). Of the generation methods known for azomethine ylides, thermolysis of aziridines was selected in this instance. The azomethine ylide... 

Whereas the thermal ring-opening reaction of oxrranes and aziridines is frequently used for generation of carbonyl ylides and azomethine ylides, the analogous procedure starting with thiiranes does not produce the expected thiocarbonyl ylides (8). However, in the case of tetraaryl-substituted thiiranes, the photolytically mediated reaction with tetracyanoethylene (TCNE) is believed to occur via a single electron transfer (SET) mechanism, also involving a thiocarbonyl ylide as a likely intermediate (75,76) (Scheme 5.14). 

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