Aziridines reagents

Quinazolinone annelation of the 0-protected chiral pyrolidinone 74 (derived from L-aspartic acid) forms pyrrolo[2,l-fc]quinazohn-9(lH)-one 75 subsequent desilylation affords (S)-(-)-vasicinone 10, which is identical with the natural /-product (Scheme 16) [212,213]. Asymmetric oxidation of de-oxyvasicinone 11 (via the imine enolate) with either (R)- or (S)-Davis ox-aziridine reagent (lO-camphorsulfonyloxaziridine) [214,215] provides a convenient route to both enantiomers, thus confirming the recently revised stereochemistry of natural vasicinone (Scheme 16) [212,213]. Recently another approaches to optically active pyrrolo[2,l-fo]quinazolinones 10 have been reported by Kamal et al. (lipase-catalyzed resolution) [56], and Argade et aL (asymmetric synthesis from (S)-acetoxysuccinic anhydride) [216]. One-pot synthesis of 11, and related alkaloids has been also developed by utilizing microwave irradiation by Liu et al. [217]. Biogenetically patterned short-step synthesis of pyrroloquinazolinone alkaloids is well established by On-aka [218], and for many other synthesis, see the references cited in these papers. 

The first organocatalytic asymmetric aziridination reactions of electron-deficient olefins made use of either (i) a chiral tertiary amine combined with a 0-phosphinyl or sulfonyl hydroxylamine for the in situ generation of aminimides as aziridination reagents [133, 134], or (ii) a quaternary salt of cinchona alkaloids in phase-transfer catalysis in combination with ethyl nosyloxycarbamate [135], A-acyl A-aryl... 

Substituted 2-haloaziridines are also known to undergo a number of reactions without ring opening. For example, displacement of chlorine in (264) with various nucleophilic reagents has been found to occur with overall inversion of stereochemistry about the aziridine ring (65JA4538). The displacements followed first order kinetics and faster rates were noted for (264 R = Me) than for (264 R = H). The observed inversion was ascribed to either ion pairing and/or stereoselectivity. 

Aziridines can best be obtained by ring closure of amine derivatives which contain a tm 5-oriented leaving group at the -position, see (89). The variable conformational and steric influences in the steroid skeleton limit the generality of a particular synthetic method and necessitate a selection of reagents based on the position of fusion of the aziridine ring. 

Reagent-controlled aziridination using camphor-derived chiral sulfide 47 has been reported with ee values of 84-98% for the trans isomer although the tram cis ratio was... 

The Hoch-Campbell aziridine synthesis entails treatment of ketoximes with excess Grignard reagents and subsequent hydrolysis of the organometallic complex. ... 

In 1934, French chemist Hoch reported that the action of phenylmagnesium bromide on the oxime of propiophenone (3) at elevated temperature gave two products. One was aziridine 4 and the other was erroneously assigned as hydroxylamine 5. In the subsequent years (1939 onward), Campbell at the University of Notre Dame determined that the purported hydroxylamine 5 was actually P-hydroxylamine 6. The scope of the Grignard reagents was extended to both aryl and aliphatic Grignard reagents. 

Secondary aziridines bearing a trifluoromethyl group were prepared via the Hoch-Campbell reaction of Grignard reagents and oximes bearing a trifluoromethyl... 

When both a-positions of the oxime possess active hydrogen, the regiochemistry of the Hoch-Campbell reaction prefers the side with more available hydrogens— indicating the process is kinetically controlled. In case of oxime 36, azirine 37 was not formed. Instead, azirine 38 was obtained exclusively. Addition of the third equivalent of the Grignard reagent delivered aziridine 39 as a mixture of two diastereomers. 

The Hoch-Campbell reaction of a-hydroxy ketoximes do not alter the course of the reaction although deprotonation probably took place concurrently for both the alcohol and the oxime. Treatment of oxime 40 afforded aziridine 42 in 30%, presumably via the intermediacy of azirine 41. a-Keto ketoximes would behave similarly to the a-hydroxy ketoximes in the Hoch-Campbell reaction after addition of the first equivalent of the Grignard reagent to the ketone. Therefore, the reaction between a-keto ketoxime 43 and phenylmagnesium bromide gave aziridine 45 in 41% yield, presumably via the intermediacy of azirine 44. 

The substrate scope is limited, as electron-withdrawing groups (X = p-N02 or p-CF3) on the aromatic substituent are not tolerated. However, this route does provide valuable intermediates to unnatural a-amino phosphonic acid analogues and the sulfimine can readily be oxidized to the corresponding sulfonamide, thereby providing an activated aziridine for further manipulation, or it can easily be removed by treatment with a Grignard reagent. 

Of course, the key limitation of the ylide-mediated methods discussed so far is the use of stoichiometric amounts of the chiral reagent. Building on their success with catalytic asymmetric ylide-mediated epoxidation (see Section 1.2.1.2), Aggarwal and co-workers have reported an aza version that provides a highly efficient catalytic asymmetric synthesis of trans-aziridines from imines and diazo compounds or the corresponding tosylhydrazone salts (Scheme 1.43) [68-70]. 

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