Aziridines reaction with alkynes

Lewis Acid-catalyzed [3+2] Cycloaddition. The title compound efficiently catalyzed an efficient and highly regiose-lective 1,3-dipolar cycloaddition reaction of alkynes and N-tosylazomethine ylides (eq 36). Cleavage of the C-C bond of iV-tosyl aziridines under mild conditions was catalyzed by Sc(OTf)3, affording the Af-tosylazomethine ylides. The reaction proceeds smoothly with various internal alkynes to afford the desired cycloadducts in moderate to good yields. 

In terms of miscellaneous reactions associated with aziridine synthesis, a ruthenium porphyrin catalyst was reported to facilitate a unique three-component coupling of nitroarenes with alkynes and a-diazo compounds to produce multifunctional aziridines (14OL1048). Pictured below is an intriguing palladium-catalyzed C-H bond activation/amination leading to the selective transformation of an aminolactone methyl group adjacent to an unprotected secondary amine into an aziridine (14NAT129). 

In order to synthesize alkyne 223, enantioenriched ethynylaziridme 220 was prepared by a known four-step sequence (762) from (S)-Gamer s aldehyde (765,164). A reductive coupling reaction (765,166) of the aziridine 220 with formaldehyde in the presence of Pd(Ph3)4 and Inl furnished the 2-ethynyl-l,3-amino alcohol 221. Protection of 221 as benzylidene acetal gave the alkyne 222, which was converted in the next step to the corresponding iodoalkyne 223 (767). 

Azides are very versatile and valuable synthetic intermediates, known for their wide variety of applications, and have been employed for the synthesis of a number of important heterocyclic compounds. Azides also represent a prominent class of 1,3-dipoles, and their cycloaddition to multiple tt-bonds is an old and widely used reaction (1988CR297). The dipolar cycloaddition of an azide to an alkene furnishes a triazoline derivative (2003MI623). Azide-alkene cycloadducts can extrude nitrogen at elevated temperatures to form aziridines or imines, depending upon the substrate and reaction conditions. The cycloaddition of azides with alkynes affords triazolidine derivatives which have been a focus in the area of chemical biology and have received much recent attention (2008AGE2596, 2008CR2952). In this section of our review, we recount some developments of the 1,3-dipolar cycloaddition reaction of azides that have been used for the synthesis of various alkaloids. 

More examples of dual-functionalized reagents inclnde the reaction of 2-acyl-aziridines 93 with azides and alkynes. In this case, a three-component synthesis of 2-imino-5-arylidene-3-pyrrolines 94 was achieved snccessfnlly (Scheme 5.61) [61]. 

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

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) . 

Starting from alkynes, cyclopropenes were obtained under mild reaction conditions at room temperature (30-51 %). Aziridines were isolated in 40-90 % yield with catalyst 15 using [(p-tolylsulfonyl)imino]phenyliodinane. Phi = NTs. The first chiral tris(pyrazolyl) ligand was prepared as early as 1992 by Tolman and co-workers starting from a camphor-pyrazole derivative and... 

The oxidation by lead(IV) acetate of iV-aminophthalimide and of several IV-aminolactams leads to the foimation of intermediates which do not undergo fragmentation or rearrangement, but which can be intercepted by alkenes, alkynes, sulfoxides and other nucleophiles. The reactions have proved particularly useful for e synthesis of aziridines from a variety of alkenes. The mechanism of these reactions has commonly been assumed to require the intermediacy of aminonitrenes, but this is probably not the case. Atkinson and Kelly have shown that oxidation of the aminolactam (25) by lead(FV) acetate at -20 C leads to the formation of an unstable IV-acetoxy compound. This is the species which can form aziridines with alkenes. The mechanism shown in Scheme 18, which is analogous to that for the epoxida-tion of alkenes by peroxy acids, has been proposed for the aziridination process. 

Alkynes and allenes also react with amides. Phenylthiomethyl alkynes were converted to A-Boc-A-phenylthio allenes with Boc azide and an iron catalyst. The palladium-catalyzed reaction of an allene amide, with iodobenzene, leads to A-sulfonyl aziridines having an allyhc group at Other allene A-tosylamines... 

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