Aziridine desymmetrization

In 2007, AntiUa and coworkers described the Brpnsted add-catalyzed desymmetrization of me yo-aziridines giving vicinal diamines [75]. hi recent years, chiral phosphoric acids have been widely recognized as powerful catalysts for the activation of imines. However, prior to this work, electrophiles other than imines or related substrates like enecarbamates or enamides have been omitted. In the presence of VAPOL-derived phosphoric acid catalyst (5)-16 (10 mol%) and azidotrimethylsilane as the nucleophile, aziridines 129 were converted into the corresponding ring-opened prodncts 130 in good yields and enantioselectivities (49-97%, 70-95% ee) (Scheme 53). 

Lastly, Antilla has disclosed a novel asymmetric desymmetrization of a wide range of aliphatic, aromatic, and heterocyclic meso-aziridines with TMS-N3 promoted by 11 and related 12 (Scheme 5.31) [56]. Uniquely, this is one of only several reports of electrophilic activation of nonimine substrates by a chiral phosphoric acid. Mechanistic studies suggest that silylation of 11 or 12 by displacement of azide generates the active catalytic species A. Consequently, the aziridine is activated through coordination of it carbonyl with chiral silane A to produce intermediate B. Nucleophilic ring opening by azide furnishes the desymmetrized product and regenerates 11 or 12. 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in transepoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)6-65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

Shortly thereafter, Aiken and coworkers also reported that quinine (4) could be used as a catalyst (50mol%) to promote the methanolytic desymmetrization of the meso-epoxy anhydride 8a to give the lactone 9a in 57% yield and 76% ee (Scheme 11.6) [4]. Lowering the reaction temperature to 0 or —30 °C did not result in any increase in selectivity. meso-Aziridine anhydride 8b was also tested under similar reaction conditions, but a lower enantioselectivity (40% ee) was obtained (Scheme 11.6). 

Scheme 3.57 Enantioselective desymmetrization of meso aziridines with azide.

Antilla and co-workers reported desymmetrization of meso-aziridines catalyzed by the (R)-VAPOL-derived phosphoric acid 26 (Equation 10.50, Figure 10.22) [96],... 

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides 13BJ01677. 

DESYMMETRIZATION OF AZIRIDINES WITH SULFUR AND SELENIUM REAGENTS... 

The direct introduction of two contiguous stereogenic centers in a stereocontrolled fashion within a molecule is a particularly appealing strategy in asymmetric synthesis. The desymmetrization of readily available achiral w. so-compounds like epoxides and aziridines represents a powerful example to straightforwardly prepare a variety of 1,2-amino alcohols, 1,2-amino thiols, 1,2-diols, and 1,2-diamines [87],... 

We reported that commercially available a,a-L-diphenyl prolinol 17d promoted the desymmetrization of wejo-aziridines with arene thiols (Scheme 14.30) [90]. A -Aroyl protected aziridines were converted into the product in good yield and moderate ee. 

SCHEME 14.29. Pase transfer and quinine catalyzed desymmetrization of wcio-aziridines with arene thiols. 

SCHEME 14.30. Desymmetrization of me o-aziridines with thiols catalyzed by a,a-L-diphenyl prolinol. 

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