An aziridinomitosene skeleton, a basic core of mitomycin antibiotics, was straightforwardly prepared from N-(p-toluenesulfonyl)indole-2-carboxaldehyde in 16% overall yield by successive reactions of guanidinium ylide-mediated aziridination, InCl 3 -catalyzed epimerization of trans-3-(indol-2-yl)aziridine-2-carboxylate, leading to the cis-derivative, and dehydrative cyclization.Introduction. -Mitomycins are antibiotics isolated from Streptomyces species [1], and mitomycin C, among them, has clinically been used as an anticancer drug [2]. Aziridinopyrroloindole, composed of a 6-5-5-3 ring system, is the core skeleton of mitomycin antibiotics and is generally called as either aziridinomitosane or aziridinomitosene depending upon the saturation of the indole unit. Many groups have attempted at the synthesis of mitomycin antibiotics due to their interesting biological activities, and Kishi and co-workers [3], and Fukuyama and Yang [4] have skillfully achieved total syntheses of natural mitomycins. Although various synthetic approaches to aziridinomitosane [5] and aziridinomitosene [6] skeletons have also been examined, the use of bond connection between C(3) and N(4) (cf. the atom numbering of aziridinomitosene in Scheme 1) in the final construction of the ring system has never been reported to the best of our knowledge. We have established a unique guanidinium ylide-mediated aziridination reaction of an aromatic [7] [8] or unsaturated [9] aldehyde, in which trans-3-(indol-2-yl)aziridine-2-carboxylate (trans-2; Scheme 1) could be obtained, when indole-2-carboxaldehyde (1; Scheme 1) is used as an aldehyde source. Herein, we describe a straightforward construction of a model aziridinomitosene skeleton from 3-(indol-2-yl)aziridine-2-carboxylate.Results and Discussion. -Our synthetic strategy toward the aziridinomitosene skeleton 3 or 4 is outlined in Scheme 1, in which three reactions are combined: i) Scheme 2. Trials for Aziridination of Ethyl 2-Formyl-1H-indole-3-carboxylate 7 Scheme 3. Aziridination of (Silyloxy)methyl-Substituted 1H-Indole-2-aldehydes and Trials for Epimerization of the trans-Aziridines Formed

Guanidinium Ylide Mediated Aziridination from Arylaldehydes: Scope and Limitations in the Formation of Unactivated 3-Arylaziridine-2-carboxylates. -The diastereo-and enantioselective formation of 3-arylaziridine-2-carboxylates from aryl aldehydes and guanidinium ylides is investigated. While the diastereoselectivity depends mainly on the employed aryl aldehyde, the enantiomeric excess drops significantly, when hexafluorophosphate is used as ylide counterion. -(ODA, Y.; HADA, K.; MIYATA, M.; TAKAHATA, C.; HAYASHI, Y.; TAKAHASHI, M.; YAJIMA, N.; FUJINAMI, M.; ISHIKAWA*, T.; Synthesis 46 (2014) 16, 2201-2219, http://dx.

The scope and limitations of guanidinium ylide mediated aziridinations from arylaldehydes yielding unactivated 3-arylaziridine-2-carboxylates, applicable to asymmetric synthesis, are discussed.Aziridine is the smallest nitrogen-containing heterocycle with a highly strained three-membered system. 1 Owing to its high reactivity, the aziridine unit not only plays an important role in biological actions, such as being responsible for the mode of action in the antitumor activity of mitomycin, but also is used as a versatile synthetic precursor for biologically important nitrogen-containing compounds, especially 3-substituted aziridine-2-carboxylates for amino acid derivatives through a ring-opening reaction. 2 Thus, although a variety of aziridine preparation methods involving asymmetric synthesis have been developed, they are basically classified into three approaches: 1 (1) cyclization of β-amino alcohol derivatives under nucleophilic substitution, (2) cycloaddition of carbenes to imines, and (3) cycloaddition of nitrenes to olefins. In 2001 1 , we 3 made a preliminarily report of a new synthetic method for the preparation of 3-aryl-1-benzylaziridine-2-carboxylates 5 from guanidinium salts 1, which incorporated an N-benzylglycine unit in the 2-position of an imidazolidine skeleton, and aryl-and heteroarylaldehydes 3, possibly through the corresponding guanidinium ylides 2 by treatment with a base (Scheme 1). This aziridination can be extended to an asymmetric version by introduction of chiral center(s) in the guanidinium templates (e.g., L = Ph). In this unique cycle, unactivated 3-arylaziridine-2-carboxylates 5 are generated with excellent to moderate stereoselectivity depending upon the choice of arylaldehydes 3, and urea 6 is also co-produced as a recyclable synthetic precursor for the guanidinium salt 1. In general, trans-aziridines are efficiently obtained with satisfactory enantioselectivity when arylaldehydes bearing an electron-donating group such as piperonal [3,4-(methylenendioxy)benzaldehyde, 3a] are used as the electrophile, whereas cis-aziridines are obtained as the major isomer when arylaldehydes bearing an electron-withdrawing group, such as 4-chlorobenzaldehyde (3g), are used. Based on these stereochemical results, we tentatively postulated a mechanism for the asymmetric induction through spiro intermediates 4 formed by formal 1,3-dipolar cycloaddition between the guanidinium ylide 2 and an arylaldehyde 3. Precise examination of this asymmetric aziridination using a variety of 4-substituted benzaldehydes allowed us to propose more reasonable mechanisms to cover the overall aziridine preparation from guanidinium ylides by application of the Hammett relation. 4 Furthermore, we succeeded in expanding this aryl aziridination to an alkenyl (or alkynyl) version by the use of unsaturated aldehydes 5 in place of arylaldehydes as the electrophile, and fully characterized a spiro intermediate like 4 in the reaction with α-bromocinnamaldehyde as a crystalline product. 5b Thus, although we have fragmentally repo...