1605-08-9Relevant academic research and scientific papers
Reactivity of aziridinomitosene derivatives related to FK317 in the presence of protic nucleophiles
Wiedner, Susan D.,Vedejs, Edwin
experimental part, p. 1045 - 1055 (2012/03/26)
The syntheses and reactivity of N-TBDPS and N-trityl protected derivatives of an aziridinomitosene corresponding to FK317 are described. New reactivity patterns were observed for these highly sensitive and functionally dense heterocycles under mild nucleophilic conditions approaching the threshold for degradation. Thus, the silyl or trityl protected aziridinomitosene reacted with Cs2CO3/CD3OD to give isomeric products where substitution occurred at C(10) and C(9a) (mitomycin numbering) providing a CD3 ether and a CD3 hemiaminal, respectively. These findings show that heterolysis at C(10) is faster than at aziridine C(1), in contrast to the behavior of typical aziridinomitosenes in the mitomycin series. The labile N-TBDPS hemiaminal and the more stable N-trityl hemiaminal resemble the mitomycin K substitution pattern. A reagent consisting of CsF in CF 3CH2OH/CH3CN desilylated a simple N-TBDPS aziridine but caused nucleophilic cleavage at C(1) as well as C(10) without cleavage of the N-TBPDS group in the fully functionalized penultimate aziridinomitosene. The high reactivity of the C(10) carbamate with nucleophiles precludes the use of deprotection methodology that requires N-protonation for fully functionalized aziridinomitosenes in the FK317 series.
Reactions of N-acylaziridines with sodium metal and sodium naphthalenide. Elimination of olefines
Lin, Pen-Yuan,Bellos, Konstantinos,Werry, Juergen,Assithianakis, Petros,Weiss, Rainer,Mall, Thomas,Bentz, Gunther,Stamm, Helmut
, p. 270 - 278 (2007/10/03)
Reactions of N-acylaziridines 1a-g (N-benzoyl except 1d) with sodium or naphthalenide N.- in THF provide a variety of products that usually arise via the aziridino ketyls 2. Homolytic ring opening of 2 generates the amidatoalkyl radicals 3. Only with a very short reaction time were small amounts of benzil or benzoylnaphthalenes obtained indicating a reversible trapping of 2 by dimerization or coupling with N.-. Homolysis of 2 produced always the more stable 3 apart from reactions of monomethylaziridines 1c,d where the primary radical i-3c,d is kinetically favoured. The amides R1CONHCHR4CHR2R3 (9, isopropylamides i-9c,d from 1c,d) were usually the main products. 9 arise from 3 either by H atom abstraction from THF (probably in sodium metal runs) or by reduction of 3 to carbanions 5 that abstract a proton from THF (N.- runs). Addition of 5a (R2-4 = H) to 1a gives finally the ketone 8a. Self reaction of primary radical 3a is dimerization. Self reaction of tertiary or secondary radicals is disproportionation when an allylamide arises. This isomerizes to an enamide unless it is conjugated. R2R3C=CHR4 and R1CONH2 arise (probably) always. The mechanism, possibly a cyclic process of anion 6, is not clear. Johann Ambrosius Barth 1996.
Single Electron Transfer versus Nucleophilic Ring Opening in Reactions of Cis-Trans Pairs of Activated 2-Phenylaziridines. Strong Influence of Nitrogen Pyramid for N-Benzoylaziridines
Falkenstein, Reinhard,Mall, Thomas,Speth, Dieter,Stamm, Helmut
, p. 7377 - 7381 (2007/10/02)
Activated 2-phenylaziridines with a second substituent R in position 3 were made to react with xanthyl anion X(1-).Nucleophilic ring opening is the only reaction that occurs with sulfonyl activation.The analogous N-benzoylaziridines 1 undergo this type of ring opening when the two substituents Ph and R are trans.The cis isomers (cis-1, Ph and R cis) react in this manner to a negligible extent if any.The (nearly) exclusive ring cleavage reaction of cis-1 is C-N homolysis of an intermediate ketyl formed by single electron transfer (SET) from X(1-).This cis-trans phenomenon is in accordance with the hypothesis that the two competing reactions depend in an opposite manner on the steepness of the nitrogen pyramid.A predominant or exclusive final result of SET is reductive aziridine opening and dimerization of the xanthyl radical X(.).Formation of both diastereomers of the amidoethylated xanthene in one case (R = Me) is evidence for a cross combination of X(.) with the radical formed by homolytic ring opening.Cross combination is also a likely path for R = H (no cis-trans isomerism), in addition to reductive ring opening. cis-Aziridines with dimethylcarbamoyl on nitrogen do not react via SET since the ketyl is not stabilized and therefore difficult to generate.Carbonyl attack on both types of acylaziridines competes more or less successfully with the two ring cleavage reactions.
N-S Cleavage Is Faster Than Homolytic Ring Opening in Single-Electron Transfer to Some N-Sulfonylaziridines. Competition between SN2 and SET
Bellos, Konstantinos,Stamm, Helmut,Speth, Dieter
, p. 6846 - 6849 (2007/10/02)
The radical anions of the N-sulfonylaziridines, 1a,b and 3 undergo N-S cleavage in place of homolytic ring opening as is demonstrated by reactions with anthracenide A*-.Nucleophilic ring opening of the sulfonylaziridines 1a,b and 3 by the carbanions AH-, X-, and Fl- of dihydroanthracene, xanthene, and fluorene, respectively, proceeds with the expected regioselectivity and is slow enough to allow some competition by a single-electron transfer (SET) initiated N-S cleavage, which provides the desulfonated aziridines and bixanthenyl X-X or bifluorenyl Fl-Fl, respectively.The SET path is favored by light.The competition is in favor of SET to the exclusion of the nucleophilic opening when trityl anion reacts with 1a.The twice-found byproducts 11 and 12 require the azirine intermediate 15, which is, at least formally, generated by elimination of TsH from 1a in a non-SET reaction.
