Ring Opening of Epoxides and Aziridines

Shibasaki and coworkers have applied heterobimetalhc gallium complexes to the desymmetrization of meso epoxides using phenolic nucleophiles. Complex 35 is 

Zhu and coworkers have applied another Ga-based system to the desymmetriza-tion of meso epoxides using acetylide anions as nucleophiles. A complex generated from Mc3Ga and a novel salen provides modest selectivities and yields using phenylacetyhde as the nucleophile  

Inaba and coworkers reported that a Ti-BINOL complex is an effective catalyst for the desymmetrization of epoxide 44 using primary amines as nucleophiles. Of significant note is the efficiency of this reaction, with only 1 mol% catalyst necessary to attain high yields and selectivities [Eq. (10.11)]. Unfortunately, this epoxide is uniquely effective in this reaction. Cycloheptene oxide, dihydrofuran oxide, and an acyclic version of 44 each provided negligible yields under these reaction conditions  

Ring opening of meso aziridines has also been investigated. Jacobsen and coworkers found that tridentate Schiff base Cr(III) complex 62 is efficient at inducing good levels of enantioselectivity in the azidolysis of aziridines 60 [Eq. (10.15)]. Alkyl-substituted aziridines were found to work best with the electron-deficient dinitrophenylmethyl providing optimal results  

Miiller and Nury examined aziridine ring opening using Grignard reagents as nucleophiles. They found that the reaction proceeds in moderate selectivities in the presence of copper catalysts such as 69  

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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]. 

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. 

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. 

A MeO bis(pinacolato)diboron adduct ring opens vinyl epoxides and aziridines in the presence of PCy3 and NaOMe in THF giving trans-1,4-hydroxy allyl boronates and trawi-l,4-amino allyl boronates, respectively, in an Sf 2 reaction. Yields range from 71 to 99%. If CuCl is added to the reaction mixture, only the c -l,2-hydroxyboronate is formed in an 5 2 reaction. The results of DFT calculations suggesting the transition state for the reaction on the epoxides is early, while that for the attack on the aziridines is late and that AG is 9-lOkcalmor lower for the aziridine reaction, are consistent with the experimental findings for these reactions. 

Jacobsen reported in 1990 that Mnm complexes of chiral salen ligands (41) were the most efficient catalysts available for the enantioselective epoxidation of alkyl- and aryl-substituted olefins.118 This stimulated a rapid development in the chemistry and applications of chiral SB complexes, which offer promising catalytic applications to several organic reactions, such as enantioselective cyclopropanation of styrenes, asymmetric aziridination of olefins, asymmetric Diels-Alder cycloaddition, and enantioselective ring opening of epoxides.4,119... 

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. ... 

Miscellaneous. Ring opening of a variety of epoxides and aziridines with NaNs in the presence of Oxone in high yields has been accomplished (eq 90). The specific role of Oxone is unclear, however, no ring opening takes place in its absence. It is suggested that the results are due to Oxone s acidic nature. 

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... 

Miscellaneous. Ring opening of a variety of epoxides and aziridines with NaNs in the presence of Oxone in high yields... 

The use of room temperature ionic liquids offers the advantage of an easy recycling of the catalyst [133] with sometimes a significant rate acceleration and an improvement of the selectivity [134]. Such an approach has been reported with Bi(0Tf)3 %H20 for the FC acylation of aromatics [50a,b], the synthesis of ds-aziridine carboxylates [135], aldol additions [32d,e], and various ring opening of epoxides [86b, 136]. 

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. 

The ring opening of epoxides by inorganic azides is the initial step of a general synthetic route to aziridines. Because enantiopure epoxides are readily available by Sharpless epoxidation and other methods, their ring opening by azide ions provides one of the best approaches to the synthesis of enantiopure aziridines. The stereochemistry of the aziridines can be reliably predicted on the basis of the mechanisms of the steps involved. 

Ammonium hexanitratocerate(IV) can be used as a catalyst for the ring opening of epoxides in presence of water, thiols or acetic acid (scheme 21) (Iranpoor et al., 1991). Epoxides react in presence of an excess of nitrate ions and a catalytic amount of ammonium hexanitra-tocerate(IV) in acetonitrile to /3-nitrato alcohols (Iranpoor and Salehi, 1995). A combination of ammonium hexanitratocerate(IV) and A-bromosuccinimide (NBS) transforms epoxides into a-hydroxy ketones (scheme 22) (Surendra et al., 2005). Aziridines give a-aminoketones under the same conditions. 

Epoxide Opening. - Ring-opening of epoxide 14 by azide was used in a new synthesis of methyl 3-aniino-3,4-dideoxy-P-D-j(y/o-hexopyranoside 17 (Scheme 4), which was required for the preparation of nitrosourea derivatives. Intermediate azides 15 and 16 were obtained in a 3 2 ratio. An alternative route to epoxide 14 was also reported. The D-r/bo-aziridine 19 was obtained from the D-lyxo-epoxide 18 (Scheme S) and used in the synthesis of epimino-nucleoside analogues (see Chapter 20). Syntheses of methyl 2,3-rra/u-aminofluoropentofuranosides from 2,3-cpoxides is covered in Chapter g. 

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. 

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