Letter Cite This: Org. Lett. 2018, 20, 3587−3590
pubs.acs.org/OrgLett
Chirality Transfer in Rhodium(I)-Catalyzed [3 + 2]-Cycloaddition of Vinyl Aziridines and Oxime Ethers: Atom-Economical Synthesis of Chiral Imidazolidines Tao-Yan Lin, Hai-Hong Wu, Jian-Jun Feng,* and Junliang Zhang* Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663 N. Zhongshan Road, Shanghai 200062, P. R. China
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S Supporting Information *
ABSTRACT: A highly efficient and stereoselective synthesis of enantioenriched imidazolidines by rhodium-catalyzed intermolecular [3 + 2] cycloaddition reaction of chiral vinyl aziridines and oxime ethers has been successfully developed. Notably, both aldoximes and ketoximes are suitable substrates to afford the corresponding chiral imidazolidines in high yields with good stereoselectivity. This transformation represents an unprecedented example that utilizes ketimine derivatives as an aza-[2C]-component in cycloadditions of vinyl aziridines.
C
methods for the syntheses of functionalized imidazolidines with excellent stereoselectivity is still desirable.3 Aziridines, the smallest nitrogen-containing heterocycle, are increasingly being exploited as useful building blocks for the synthesis of various N-heterocycles.4 Among them, the transition-metal-catalyzed [3 + 2]-cycloadditions of aziridines with imine derivatives represent powerful tools enabling quick and efficient access to imidazolidines in an atom-economical fashion.5,6 However, almost all previous studies on this topic have been focused on 1,3-dipolar cycloadditions of either aryl or alkyl aziridines by selective C−C and C−N bond cleavage which gave imidazolidines in racemic form.5 In contrast, [3 + 2]-cycloadditions involving vinyl aziridines giving imidazolidines derivatives are rarely reported.7 The additional olefin moiety installed in the imidazolidine skeleton would increase the structural flexibility in view of a tremendous number of reactions associated with olefins. In 2016, Booker-Milburn and co-workers completed an elegant work on palladium-catalyzed [3 + 2]-cycloadditions of cyclic vinyl aziridines with aldimines (Scheme 1, eq 1).7a However, they reported only four examples with moderate yields and regioselectivity in racemic form. Very recently, a palladium-catalyzed intermolecular [3 + 2]-cycloaddition of vinyl aziridine and cyclic N-sulfonyl imines was developed by the group of de Figueiredo (Scheme 1, eq 2).7b However, due to a rapid π−σ−π interconversion of the π-allyl palladium intermediate, only 19% ee of the product was obtained from 80% ee of vinyl aziridine. To the best of our knowledge, there is no report on the [3 + 2]-cycloadditions of vinyl aziridines and ketoximes. As part of our continuing program in the development of cycloaddition reactions of vinylaziridines,8 we became interested in whether aldoximes and ketoximes could be used as two-atom components in
hiral imidazolidines are ubiquitous structural motifs found in an array of biologically active natural products and pharmaceuticals (Figure 1).1 For example, alchorneine and
Figure 1. Biologically active privileged imidazolidines scaffolds.
isoalchorneine are structurally based on an imidazolidine scaffold and alchorneine, which has been proposed as a potential spasmolytic agent in dogs.1b BMS-564929 is an orally active and selective androgen receptor modulator.1c Cyanogramide, an unprecedented alkaloid, could reverse the adriamycininduced resistance of K562/A02 and MCF-7/Adr cells efficiently.1d In addition, they are utilized as versatile building blocks in organic and bioorganic chemistry as well as synthetic reagents such as chiral ligands and catalysts.2a−g In particular, imidazolidines can be easily transformed into imidazoles, which are well-known scaffolds in many significant biomolecules.2h−k Because of these impressive activities and applications, a number of scientists have been engaged in the synthesis of imidazolidines. However, the development of simple and novel © 2018 American Chemical Society
Received: May 1, 2018 Published: June 4, 2018 3587
DOI: 10.1021/acs.orglett.8b01378 Org. Lett. 2018, 20, 3587−3590
Letter
Organic Letters Scheme 1. Reactions of Vinylaziridine Reactions of Vinylaziridines with Imine Derivatives
Table 1. Selected Examples from Optimization of the Reaction Conditionsa
entry
variation
yieldb (%)
eec (%)
drd
1 2e 3e 4 5e 6 7 8 9 10 11
none [Rh(NBD)2]BF4 [Ir(COD)Cl]2 [Rh(η6-C10H8)(COD)]SbF6 AgClO4 instead of AgSbF6 AgOTf instead of AgSbF6 reaction was run at 25 °C reaction was run at 0 °C reaction was run at −10 °C CH2Cl2 instead of DCE toluene instead of DCE
95 10
