Reactions of Epoxides and Aziridines

Catalytic ring expansion ofthiiranes, aziridines, and oxiranes 13SL787. Organocatalysis in synthesis and reactions of epoxides and aziridines 13RCA11385. 

Altihough many of the early examples of the carbonylation of heterocycles included reactions of tetrahydrofurans, oxetanes, and azetidines, the majority of recent work has focused on the reactions of epoxides and aziridines. At this point, the ring-expansive reactions of epoxides are more general than the reactions of aziridines and occur imder milder conditions. Prior to 1994, ring-expansive carbonylation of epoxides was restricted to a few substrates. The patent by Droit and Kragtwijk s in 1994 inspired further work on these t)rpes of carbonylations, and tiiis work led to dramatic improvements in reaction scope. 

This chapter describes the chemical Hterature of aziridines and epoxides for the year 2013. As in previous years, this account does not provide a complete list of all uses and syntheses of aziridines and epoxides. Instead, the aim of this report is to provide an overview of synthetically valuable and intriguing methods that pertain to the reactions and synthesis of three-membered heterocycles. In particular, it should be noted that a review discussing organocatalysis in the synthesis and reactions of epoxides and aziridines was reported during the past year (13MI11385). 

Fan, R.-H. and Hou, X. L., Rfficient ring-opening reaction of epoxides and aziridines promoted by trib-utylphosphine in water, /. Org. Chem., 2003,68, 726-730. 

Click chemistry is a chemical concept enunciated by Barry Sharpless, Scripps Research Institute, USA, in 2001, which highlights the importance of using a set of powerful, highly reliable, selective reactions under simple reaction conditions to join small molecular units together quickly for the rapid synthesis of new compounds via heteroatom links and create molecular diversity. Several types of reactions have been identified that fulfill the criteria- thermodynamically favored reactions that lead specifically to one product such as nucleophilic ring opening reactions of epoxides and aziridines, nonaldol type carbonyl reactions, additions to carbon-carbon multiple bonds, Michael additions, and cycloaddition reactions. The best-known cHck reactions are the copper-catalyzed reaction of azides and alkynes or the so-called CuAAC reaction and the thiol-ene reaction. 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

Sn2 substitution reactions of alkyl halides with hard nucleophiles such as alkyl anions can be achieved most readily with the aid of organocopper chemistry [95]. Sn2 reactions with epoxides and aziridines are also synthetically useful [96]. The... 

Stereoselective addition of allyl metal reagents to various functionalities is an important reaction in organic synthesis [32, 33]. The allylation of epoxides and aziridines with allyltin reagent is catalyzed by Lewis acids. Even though many Lewis acids have been reported to catalyze this reaction, Bi(OTf)3 is distinct because it avoids the formation of byproducts and is also environmentally more compatible. It catalyzes the reaction of aryl epoxides with tetraallyltin to afford the corresponding homoallyllic alcohol [34]. 

Catalytic ring opening of epoxides and aziridines was also observed (Eq. 27). The acetone cyanohydrine reaction provided j8-hydroxy nitrile and / -amino nitriles, with the lanthanide isopropoxides exhibiting a higher reactivity than Et3N [233]. 

This review covers the chemical literature on epoxides and aziridines for the year 2007. As in previous years, this review is not comprehensive but rather covers a selection of synthetically useful and interesting reactions. Three-membered ring systems, epoxides and aziridines in particular, are excellent synthetic intermediates. This is largely due to their ability to be converted into other functional groups such as diols, diamines, and amino alcohols to name but a few. The chapter has been divided into two sections, one covering epoxides and the other covering aziridines. Each of these sections has been further divided into two additional sections, one on the synthesis of the heterocycle and one on the reactions of the heterocycle. There is some overlap between methods for the synthesis of epoxides and aziridines and any overlap has been noted in the text. 

Finally, a racemic cyclopropanation process has also been developed that utilizes an iron Lewis acid catalyst (72) that presumably proceeds through an iron carbene intermediate (73) (Scheme 28). The catalyst is activated by reaction with diazo compounds to produce an intermediate (74) that loses dinitrogen see Dinitrogen Dinitrogen Complexes) to afford the cyclopropane. This chemistry has been extended to the production of epoxides and aziridines and has recently been reviewed. ... 

Lanthanide isopropoxides were introduced as the first-generation alkoxide-type precatalysts (Structures 1-3) [133]. They proved to be more effective in the catalytic ring-opening of epoxides and aziridines than Et3N [134]. The acetone cyanohydrin reaction provided 5-hydroxynitriles and /3-aminonitriles. Strong basicity of the lanthanide isopropoxides is considered to catalyze the transhydrocya-nation effectively from acetone cyanohydrin to several aldehydes and ketones [135]. YbBu3 exhibited similar catalytic activity in this reaction. 

The transition-metal-catalyzed carbonylation reaction has been extensively investigated, and especially the carbonylative ring expansion reaction of strained heterocycles has been shown to be a useful and efficient procedure to synthesize lactams, lactones, and thiolactones.203 The carbonylation of epoxides and aziridines 450 is a powerful tool to construct the /Mactone and /Mactam skeletons 451 (Scheme 142).204 This type of reactions can be regarded as a hetero-[3 + 1]-cycloaddition. 

Ring cleavage. Catalyzed hy Sc(OTf)3, alcoholysis of epoxides and aziridines proceeds at room temperature. The ring opening of mei oepoxides is rendered asymmetric if a chiral ligand such as 1 is added to the reaction medium. Lactones give polymers via alcoholysis. ... 

Enantioselective vanadium and niobium catalysts provide chemists with new and powerful tools for the efficient preparation of optically active molecules. Over the past few decades, the use of vanadium and niobium catalysts has been extended to a variety of different and complementaiy asymmetric reactions. These reactions include cyanide additions, oxidative coupling of 2-naphthols, Friedel-Crafts-type reactions, pinacol couplings, Diels-Alder reactions, Mannich-type reactions, desymmetrisation of epoxides and aziridines, hydroaminations, hydroaminoalkylations, sulfoxida-tions, epoxidations, and oxidation of a-hydroxy carbo) lates Thus, their major applications are in Lewis acid-based chemistiy and redox chemistry. In particular, vanadium is attractive as a metal catalyst in organic synthesis because of its natural abundance as well as its relatively low toxicity and moisture sensitivity compared with other metals. The fact that vanadium is present in nature in equal abundance to zinc (albeit in a more widely distributed form and more difficult to access) is not widely appreciated. Inspired by the activation of substrates in nature [e.g. bromoperoxidase. 

These reactions are useful as processes to form building blocks for pol)mier s)mthesis and organic s5mthesis. The p-lactones and p-lactams formed by the carbonylation of epoxides and aziridines are monomers that can be used in ring-opening polymerization. The... 

Substitutions of Sn2 type are frequently used for carbon-carbon or carbon-heteroatom bond formation. However, little attention has been devoted to the development of such reactions in water. This is likely due to concerns about competitive hydrolysis of the electrophile in water and SN2-type reactions being slower in aqueous conditions than in aprotic polar solvents due to the higher cost of desolvation of nucleophiles. We shall discuss the ring opening of epoxides and aziridines, palladium-catalyzed allylic substitutions, as well as acylations and sulfonylations of amines and alcohols. 

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