Alkaloids azomethine ylide generation

Azomethine ylide generation from oxazolidines has also been achieved by flash vacuum thermolysis (20,21). During synthetic efforts toward alkaloid central skeletal cores, Joucla and co-workers (22) revealed that flash vacuum thermolysis of oxazolidine (84) led to an intramolecular [3 + 2] cycloaddition furnishing pyrrolidine 85 in 82% as a single regio- and stereoisomer. Subsequent Dieckmann... 

Cinchona alkaloid thiourea catalyst 17 (Figure 37.2) was later employed by Gong el al. to induce the enantio- and diastereoselective 1,3-dipolar cycloaddition of azomethine ylides generated from Schiffbases and nitroalkenes [31]. This process provided straightforward access to chiral highly substituted pyrrolidines with good yields, moderate enantioselectivities (<63% ee), and excellent diastereoselectivities... 

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... 

Garner et al. [49] have synthesized the 6-exo-substituted 3,8-diazabicydo [3.2.1] octane core of DNA reactive quinocarcin alkaloid 99 by cydoaddition of the azomethine ylide 101, generated by irradiation (A. — 254 nm) of the corresponding aziridine 100, with Oppolzer s chiral acryloyl sultam (102). This produced 6-exo-subs tituted cycloadducts 103 104 in 25 1 diastereoselectivity (Scheme 8.30). 

Padwa and coworkers found that a-cyanoaminosilane 12a is a convenient synthon for azomethine ylide 15 which is extensively used in heterocyclic synthesis [7]. AgP has been adopted to generate the ylide 15 from 12a for the preparation of pyrrolidine derivative 14 (Sch. 4). Various dipolarophiles including A-phenylmaleimide (13) can be used for the cycloaddition. When iV-[(trimethylsilyl)methyl]-substituted indole 16 is reacted with AgP in the presence of maleimide 13, pyrrolo[l,2-a]indole 17 is formed in good yield, retaining the CN group [8]. A silver-bonded carbonium ion is assumed to be a reactive intermediate. Reaction of a cyano-substituted azomethine ylide, derived from (silylmethylamino)malononitrile 12b and AgP, with methyl propiolate (18) provides 3-carbomethoxy-A-benzylpyrrole (19) [9]. Epibatidine, a novel alkaloid, was successfully synthesized by employing the [3 + 2] cycloaddition of azomethine ylide with electron-deficient alkenes as a key step [10]. 

Azomethine ylides are very important 1,3-dipoles, and they are usually used to react with alkenes leading to the formation of the highly substituted pyrrolidine derivatives [17]. A novel and practical process for the 1,3-dipolar cycloaddition of azomethine ylides with alkenes had been reported by j0rgensen and coworkers [18]. They proposed that a dipol-chiral base ion pair would be generated between a-imino ester-metal complex and a cinchona alkaloid, and subsequent cycloaddition with dipolarophile would take place in a stereoselective manner (Scheme 10.13). 

Intramolecular 1,3-dipolar cycloaddition reactions normally proceed efficiently to give bicyclic products and these reactions do not require the presence of an electron-withdrawing group on the dipolarophile. Thus, in an approach to the alkaloid sarain A, the aziridine 221 was heated to generate the intermediate azomethine ylide 222, and hence, after intramolecular cycloaddition, the pyrrolidine 223 (3.143). " An alternative method for the formation of the required azomethine ylide, and which avoids the need for the prior synthesis of an aziridine ring, uses the simple condensation of an aldehyde and a primary or secondary amine. Thus, in another approach to sarain A, addition of formaldehyde to the amine 224 resulted in the formation of the cycloadduct 226 (3.144). Notice that in both cases the... 

In an approach to the stemofoUne class of alkaloids, the Martin group discovered an unusual set of conditions for generating azomethine yHdes. Oxidation of compound 186 under Swem conditions afforded a 5 1 mixture of 189 and 190 in 69% yield (Scheme 38) (2011TL2048). The formation of these two molecules can be easily rationalized via an intramolecular 1,3-dipolar cycloaddition of dipole 188, but the mechanism through which the azomethine ylide is formed under Swem conditions is not well understood. The authors proposed that the oxidized product 187a derived from 186 reacted with one of the electrophifrc species formed under the reaction... 

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