Aziridine intermediates, synthesis of natural

Aziridines in the synthesis of azomethine ylides 89AHC(45)231. Aziridines in the synthesis of natural products 86AHC(39)I81. Azirines as intermediates in pyrrole formation 87KGS1299. 3-Amino-2-//-azirines, synthesis and properties 90KGS867. Ethynylaziridines 87MI6. 

This review summarizes the application of aziridines as intermediates to the synthesis of natural products that do not contain an aziridine ring. 

Enantioselective organocatalytic a-heterofimctionalization of active methines to give versatile intermediates for the synthesis of natural products and pharmaceuticals (2002 to mid-2011) 12RCA385. Enantioselective synthesis of natural epoxyquinoids 13COS2. Enzymatic chemistry of cyclopropane, epoxide, and aziridine biosynthesis 12CRV1681. 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

Aziridines are important compounds due to their versatility as synthetic intermediates. In addition, aziridine rings are present in innumerable natural products and biologically active compounds. Nitrene addition to alkenes is one of the most well established methods for the synthesis of aziridines. Photolysis or thermolysis of azides are good ways to generate nitrenes. Nitrenes can also be prepared in situ from iodosobenzene diacetate and sulfonamides or the ethoxycarbonylnitrene from the A-sulfonyloxy precursor. 

The numerous excellent synthetic procedures published by A.C. Richardson also continue to be relied upon by contemporary organic chemists because of their great practicality and reproducibility. Indeed, a recent highly cited enantiospecific total synthesis of the antitumor agent, (—)-agelastatin A, justly testifies to this fact it exploits the remarkably useful Hough-Richardson aziridine as a key synthetic intermediate in the eventual published route to this complex natural product. 

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). 

Alkylation of aziridine in base gives the N-substituted aziridine as you might expect, but a second alkylation leads to a positively charged aziridinium salt that opens immediately to the useful bro-moamine. In this case, the product is an intermediate in the synthesis of two natural products, san-daverine and corgoine. 

Natural products, synthesis via aziridine intermediates, 39, 181 New developments in the chemistry of oxazolones, 21, 175 Nitration of phenyl-substituted heterocycles, 58, 215 Nitrenes, carbenes and, intramolecular reactions of, 28, 231... 

Mechanistic approaches to asymmetric aziridine synthesis have been carried out systematically using a variety of p-substituted benzaldehydes (Table 4.16). Two kinds of reaction mechanism, controlled by the nature of the p-substituent of aryl aldehydes, are proposed an S i-like mechanism, via cationic-like transition state for the fragmentation of intermediate adducts to aziridine products (step 2) by intramolecular nucleophihc substitution, when EDG-substituted benzaldehydes are used and an Sielectron-withdrawing group (EWG) substituted benzaldehydes are used [99]. 

---