Coupling of vinyl aziridines and phenyl isocyanate

Abstract

Thermal coupling of vinyl aziridines and phenyl isocyanate was evaluated. Although oxazolidinone products were predominant, some reactions afforded a seven-membered ring heterocycle. When Ni/ IMes was employed as a catalyst, a wider array of vinyl aziridines underwent coupling reactions. The Ni catalyzed reactions generally afforded vinyl imidazolidinones as major products.Keywords phenyl isocyanate; vinyl aziridine; N-heterocyclic carbene; nickel; imidazolidinone; oxazolidinone; tetrahydro- [1,3]diazepin-2-oneThe coupling of an isocyanate and a vinylaziridine is an effective way to access heterocyclic ring systems. Although one example of a thermal coupling has been reported, 1 these reactions are typically catalyzed by Lewis acids such as sodium iodide 2 and nickel iodide. 3 These couplings generally afford vinyl-substituted five membered imidazolidinone products. Palladium catalysts have also been used to catalyze this coupling reaction and in some cases, these couplings display high enantioselectivity. 4,5,6 In each of these cycloadditions, the vinyl group acts to enhance the reactivity of the aziridine. For example, in non-metal mediated reactions the vinyl group is an activating group. In Pd catalyzed coupling reactions, the vinyl group enhances binding of the aziridine substrate. However, in all of these cases, incorporation of the vinyl group in the heterocycle is not observed.We present here a study detailing both thermal reactions and nickel catalyzed reactions of phenyl isocyanate and vinyl aziridines. These reactions afford interesting heterocyclic products in addition to the expected vinyl substituted imidazolidinone. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptTetrahedron Lett. Author manuscript; available in PMC 2009 January 1. Published in final edited form as:Tetrahedron Lett. 2008 ; 49(27): 4306-4309. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDespite the lack of information regarding simple thermal coupling of isocyanates and vinyl aziridines, we found that N-benzyl-2-styryl-aziridine (1a) reacted readily with 3 equiv of phenyl isocyanate at elevated temperatures (equation 1). At 100 °C, the coupling proceeded smoothly and afforded 3 distinct heterocyclic products, a seven-membered product (2a), an oxazolidinone 3a, 7 and a trace amount of imidazolidinone 4a 7 (equation 1).(2)A variety of vinyl azirdines were evaluated in the thermal coupling reaction (equation 2, Table 1). 8 Electronic factors did not have much of an effect on the reaction as both para methoxy and para CF 3 s...

Regiodivergent Intermolecular [3+2] Cycloadditions of Vinyl Aziridines and Allenes: Stereospecific Synthesis of Chiral Pyrrolidines

“…Despite the fact that vinyl aziridines are increasingly being exploited as versatile building blocks in organic synthesis, the [3+2] cycloaddition of vinyl aziridine with a two‐atom partner has not been well developed . Since 2000, the groups of Alper,, Trost,, Aggarwal, Louie, and Lee demonstrated a series of [3+2] cycloadditions of vinylaziridines with heterocumulenes (e.g., isocyanates, carbodiimides, CO 2 and isothiocyanates, etc. ), thus efficiently delivering diverse five‐membered heterocycles with two heteroatoms.…”

Ring Expansions of Nonactivated Aziridines and Azetidines

“…Both thermal and metal-catalyzed reactions have been studied and compared [39], and the thermal coupling was shown to proceed nonselectively, leading to mixtures of regioisomers [42][43][44]. Interestingly, the issue of chemoselectivity was found to depend upon the stereochemistry of the starting alkene.…”

Recent Advances in the Catalytic Synthesis of Imidazolidin-2-ones and Benzimidazolidin-2-ones

“…Proposed mechanism for nickel-catalyzed reaction of aziridines with isocyanates[171].In 2008, Louie et al reported on the ring-expansion reaction of vinylaziridines and isocyanates under thermal conditions, using Ni as the catalyst[172]. If no catalyst is added and thermal conditions (100 • C) are used, no imidazolidinon-2-ones are observed, and compounds such as oxazolidinones or seven-membered heterocycles are found in the final reaction mixtures.…”