Azetidines. fluorinated

Using similar techniques, Suda et al. have fluorinated a series of 4-trimethyl-silylazetidin-2-ones in an efficient and regioselective preparation of 4-fluoro-azetidin-2-ones [45]. 

Anodic oxidation of 4-silylazetidin-2-ones in the presence of fluoride ions provides 4-fluoroazetidin-2-ones in high yields33. This fluorination is completely regioselective. Even in the case of the TV-benzyl derivative, a fluorine atom is selectively introduced into the C-4 position of the /1-lactam ring (equation 28). In contrast, unsilylated azetidin-2-ones give no fluorinated product. 

Joshi et al. [81] have incorporated azetidin-2-one moiety into indole nucleus and synthesized several fluorine containing spiro-(3-lactams (Scheme 9). The synthesis involved the condensation of primary amines with an appropriate indole-2,3-dione... 

Calculations at the MP2(Full)/6-31++G(d,p)//MP2(Full)/6-31+G(d) level of theory were used to investigate the SN reactions between ammonia and aziridine, aze-tidine, methylethylamine, and four fluorinated derivatives of aziridine.52 The results show that aziridine and azetidine have strain energies of 27.3 and 25.2 kcalmol-1, respectively, and that as a consequence they react 7.76 x 1023 and 2.30 x 1017 times faster with ammonia than does the methylene group of methylethylamine. However, even after subtracting the effect due to the release of ring strain, aziridine still reacts much faster than the other two substrates. This is because the electrostatic attraction of the charges in the product-like dipolar transition state are much greater for aziridine. 

The action of A-chlorosuccinimide, or a source of positive fluorine such as Selectfluor , in aqueous acetonitrile on the alkene 138 (R1 = Me) is to open the azetidine ring by attack at the allylic position to yield the cyclobuten-3-ol 139 (R OH, R2 = H, R3 = Me) <2003JOC5292>. Chlorosulfonyl isocyanate (CSI) reacts with 138 (R = Et) to give both a chlorobutene 139 (R1 = Cl R2 = CONH2 R3 = Et) and the bicyclic reduced pyrimidone 140 (R1 = Et). However, the action of CSI on the more substituted 2-azabicyclo[2.2.0]hex-5-ene 141 provided the reduced mono-cyclic pyrimidone 142 <2003JOC1626>. 

In the presence of alkaline metal fluorides or tertiary amines, perfluoro-olefins react with fluorine-containing keteneimines to form azetidines 25 in mild conditions (76IZV1813). The role of the catalyst seems to be the transformation of the electrophilic keteneimine into the nucleophilic mesomeric anion capable of adding at the multiple bond of the perfluoro-olefin. The addition is accompanied by cyclization generating a catalyst. 

Not only aryl fluorides can be prepared from trimethylsilanes. Regioselective electrochemical fluorination of4-(trimethylsilyl)azetidin-2-ones 10 to give 11 has also been reported (Table 5). The electrolyses of compounds 10 are carried Out using acetonitrile as solvent. The best yields of fluorinated compounds (Table 5) are obtained when triethylamine trishydrofluoride is used as the fluorine source (with hydrogen fluoride/pyridine and triethylamine bishydro-fluoride lower yields are obtained). The stereochemistry of alkylidene side chains (Table 5, entries 3 and 4) is retained during the electrolyses. High stereoselectivity is observed in some cases (Table 5, entry 6). 

Table 5. Electrochemical Fluorination of 4-(Trimethylsilyl)azetidin-2-ones Using Triethyl-aminc Trishydrofluoride ...

Not only aryl fluorides can be prepared from trimethylsilanes. Regioselective electrochemical fluorination of4-(trimethylsilyl)azetidin-2-ones 10 to give 11 has also been reported (Table 5).33... 

Four-membered heterocydes are easily formed via [2+2] cycloaddition reac tions [63] These cycloaddition reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [77d] Via this route, p lactones are formed on addition of ketene derivatives to hexafluoroacetone [777, 77S] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, l,4-benzoxazin-2-ones, l,2,4-tnazin-5-ones, and l,2,4-tnazm-3,5-diones accelerates [2+2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluorinated oxetanes are formed thermally and photochemically [779, 720] The reaction of 577-1,2-azaphospholes with fluonnated ketones leads to [2+2] cycloadducts [727] (equation 27)... 

Preparation and synthetic applications of azetidines 12H(84)223. Recent developments in the synthesis of fluorine-containing P-amino acids and P-lactams 13CJO2098. 

The same group of Japanese authors studied the photochemical reaction of fluorinated quinoxalines. Photochemical cycloadditions with quinoxaline derivative 1294 occurred and C=N double of the diazine ring, leading to the formation of azetidine derivatives (Scheme 299). The presence of trifluoromethyl group in the molecule of 1294 activated the substrate towards cycloaddion, so that even electron-deficient methyl methacrylate was introdnced in the reaction [797], In the case of ethyl vinyl ether as the alkene, the addnct 1296 also as in a case with 1289 was not stable and underwent azetidine ring-opening npon action of the solvent. Ketene was also successfully introduced in [2+2] cycloaddition with trifiuoromethyl-substituted quinoxaline derivatives [797]... 

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