Chiral Magnesium(II) Complex‐Catalyzed Enantioselective Desymmetrization of meso‐Aziridines with Pyrazoles

Abstract

A highly enantioselective catalytic protocol for the desymmetrization of meso-aziridines via ring-opening with pyrazoles is reported using an N,N'-dioxide-Mg(OTf) 2 complex as the catalyst. The corresponding trans-a-pyrazole-substituted amines were obtained in good yields and enantioselectivities (up to 99% yield and 94% ee) under mild reaction conditions. Moreover, a remarkably high asymmetric amplification was observed in the catalytic system.Enantioselective desymmetrization is a powerful strategy for the construction of complex molecules with multiple stereocentres from relatively simple meso starting materials. [1] In particular, the enantioselective desymmetrization of meso-aziridines has captured much attention for providing access to important chiral 1,2-difunctionalized molecules with vicinal stereocenters by ring opening with nucleophiles in one single step. [2] Over the past decades, many nucleophiles such as trimethylsilyl azide, [3] trimethylsilyl cyanide, [4] amines, [5] alcohols, [6] halogen, [7] etc. [8] have been demonstrated successfully for desymmetrization of meso-aziridines. As a pioneer report, Jacobsen and co-workers described the highly enantioselective ring opening of meso-aziridines, which reacted with trimethylsilyl azide to give 1,2-azidoamines in good yields with 83-94% ee under the catalysis of the chiral chromium (III)-salicylimine complex. [9] Shibasaki and co-workers subsequently provided 1,2-amidonitriles in good yields with 81-93% ee in the presence of a catalyst prepared in situ from Gd(OiPr) 3 and the chiral ligand derived from glucose in 2005. [10] Follow-ing these early reports, many excellent researches have been furnished in desymmetrization of mesoaziridines. Recently, Wang's group realized the enantioselective dearomatization reaction and [3 + 2]-cycloaddition of meso-aziridines via an in situ generated magnesium catalyst. [11] In spite of these impressive advances, there are few reports on the direct catalytic asymmetric ring-opening of meso-aziridines with pyrazoles, [12] although pyrazole motif also exists in a number of small molecules that possess diverse chemical, biological, and pharmaceutical activities. [13]

Magnesium Catalysis in Asymmetric Synthesis

“…Acyl pyridine substituents on aziridines might be appropriate for coordinating with a magnesium center; thus, different oxygen and amine nucleophiles could attack the carbon atom in the threemembered ring to furnish the asymmetric ring-opened products (Scheme 14). 43,44 Very recently, the Feng group also reported elegant asymmetric [8 + 3] cycloadditions of tropones or azaheptafulvenes (14-9) by using dioxide/Mg(II) as the catalyst, and as expected, obtained the corresponding polycyclic adducts with good results. 45 In recent studies, Feng and coworkers used a dioxide/Mg(II) system to activate alkylidene malonates, leading to the a-addition of isocyanides to activated olefins.…”

Asymmetric magnesium catalysis for important chiral scaffold synthesis

“…Notably, the azide group was also utilized as nucleophile in this work, which was an important precursor for the synthesis of types of chiral 1,2-diamines (Scheme 3b). 15…”

“…Notably, the azide group was also utilized as nucleophile in this work, which was an important precursor for the synthesis of types of chiral 1,2-diamines (Scheme 3b). 15 By developing novel bifunctional in situ magnesium catalytic strategies, our group also realized a desymmetrization reaction of meso-aziridines with tetrazoles. Good yields and enantioselective results were obtained under the Mg(II) catalytic methods.…”

Catalytic asymmetric synthesis of 1,2-diamines

“…Feng and co-workers 34 applied a similar catalyst employed in the ring opening of aziridines 20 with aniline (see Scheme 8) for pyrazoles 33 (Scheme 12). In this case, Mg(OTf) 2 and Scheme 1 Catalytic methods for the asymmetric synthesis of 1,2-diamines.…”