Catalytic epoxide opening

The first example of asymmetric catalytic ring-opening of epoxides with sp2-hybridized carbon-centered nucleophiles was reported by Oguni, who demonstrated that phenyllithium and a chiral Schiff base ligand undergo reaction to form a stable system that can be used to catalyze the enantioselective addition of phenyllithium to meso-epoxides (Scheme 7.24) [48]. Oguni proposed that phenyllithium... 

Catalytic turn-over [59,60] in McMurry couplings [61], Nozaki-Hiyama reactions [62,63], and pinacol couplings [64,65] has been reported by Fiirst-ner and by Hirao by in situ silylation of titanium, chromium and vanadium oxo species with McaSiCl. In the epoxide-opening reactions, protonation can be employed for mediating catalytic turn-over instead of silylation because the intermediate radicals are stable toward protic conditions. The amount of Cp2TiCl needed for achieving isolated yields similar to the stoichiometric process can be reduced to 1-10 mol% by using 2,4,6-collidine hydrochloride or 2,6-lutidine hydrochloride as the acid and Zn or Mn dust as the reduc-tant (Scheme 9) [66,67]. 

The preparation of cyclobutanes via the catalytic conditions can be extremely efficient provided that the radical formed after epoxide opening is sterically shielded and cyclization promoted by the Thorpe-Ingold effect. It... 

Since the seminal contributions by Nugent and RajanBabu the field of reductive C - C bond formation after epoxide opening via electron transfer has developed at a rapid pace. Novel catalytic methodology, enantio- and stereoselective synthesis and numerous applications in the preparation of biologically active substances and natural products have evolved. In brief, a large repertoire of useful and original reactions is available. These reactions are waiting to be applied in a complex context ... 

The primary type of epoxide reaction remains the nucleophilic ring-opening reaction. Research on the development of novel catalysts or catalytic systems for epoxide opening continues to be a highly active area of study. 

Therefore, we derided to initiate a program directed towards the development of a tita-nocene-catalyzed epoxide opening [3c]. Since titanocene dichloride is formed in the stoichiometric reaction after the protic quench, the challenge to be met is the regeneration of the redox-active species in situ, the fundamental requirement for a catalytic reaction. This underlying problem is depicted in Scheme 12.12. 

Abstract In the first part of this mini review a variety of efficient asymmetric catalysis using heterobime-tallic complexes is discussed. Since these complexes function at the same time as both a Lewis acid and a Bronsted base, similar to enzymes, they make possible many catalytic asymmetric reactions such as nitroal-dol, aldol, Michael, Michael-aldol, hydrophosphonyla-tion, hydrophosphination, protonation, epoxide opening, Diels-Alder and epoxi-dation reaction of a, 3-unsaturated ketones. In the second part catalytic asymmetric reactions such as cya-nosilylations of aldehydes... 

Jacobsen, E. N. Kakiuchi, F. Konsler, R. G. Larrow, J. F. Tokunaga, M. ( 1997) Enantioselective catalytic ring opening of epoxides with carboxylic acids., Tetrahedron Lett., 38 773-776. 

Snapper and Hoveyda reported a catalytic enantioselective Strecker reaction of aldimines using peptide-based chiral titanium complex [Eq. (13.11)]. Rapid and combinatorial tuning of the catalyst structure is possible in their approach. Based on kinetic studies, bifunctional transition state model 24 was proposed, in which titanium acts as a Lewis acid to activate an imine and an amide carbonyl oxygen acts as a Bronsted base to deprotonate HCN. Related catalyst is also effective in an enantioselective epoxide opening by cyanide "... 

Epoxide opening with nucleophiles occurs at the less substituted carbon atom of the oxirane ring. Catalytic hydrogenolysis yields the more substituted alcohol. The scheme below contains also an example for frans-dibromination of a C—C double bond followed by dehy-drobromination with strong base for overall conversion into a conjugated diene. The bicyclic tetraene then isomerizes spontaneously to the aromatic l,6-oxido[l0]annulene (E. Vogel, 1964). 

The selective catalytic epoxidation of alkenes has become the most important reaction catalyzed by heme proteins in organic synthesis. As described above, the monoxygenase activity of a heme peroxidase is restricted to CPO due to the open substrate access of the ferryl subunit for this enzyme. HRP catalyzes epoxidations only after mutagenetic variations, as shown for the substrate trans-P-methylstyrene [234]. An exception of this rule is the regioselective epoxidation of (T.TJ-piperylpiperidide, which is successfully catalyzed by native HRP [265]. 

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]. 

Conceptually new multifunctional asymmetric two-center catalysts, such as the Ln-BINOL derivative, LnMB, AMB, and GaMB have been developed. These catalysts function both as Brpnsted bases and as Lewis acids, making possible various catalytic, asymmetric reactions in a manner analogous to enzyme catalysis. Several such catalytic asymmetric reactions are now being investigated for potential industrial applications. Recently, the catalytic enantioselective opening of meso epoxides with thiols in the presence of a heterobimetallic complex has... 

The coupling of independent catalytic cycles for both radical generation and reduction has been realized by the combination of the titanocene catalyzed reductive epoxide opening [36—4-0] via electron transfer and the catalytic reduction of radicals after H2 activation by Wilkinson s complex [Rh(PPh3)3Cl] as shown in Scheme 16 [41—43],... 

Reaction times with the catalytic method are comparable to those obtained with the stoichiometric method and Z-disubstituted allylic alcohols can be efficiently epoxidized at —20 JC in 1 -4 hours using just 5% titanium(IV) isopropoxide and 6-7.5% tartrate (Table 4). The method is especially useful for epoxidation of alcohols that react only very slowly under normal conditions. In particular, Z-disubstituted allylic alcohols (Table 4) react at useful rates only if the reaction is warmed to —10 °C. In the catalytic procedure the absence of large quantities of titanium salts and tartrate minimize epoxide opening that would be a problem in the stoichiometric procedure at this temperature. A similar situation exists for unsymmetrical disubstituted allylic alcohols (Table 4) which are also prone to opening under the conditions of the stoichiometric method. 

An additional advantage of the catalytic methods is that reactions can be performed at higher concentration. Stoichiometric reactions are typically carried out at 0.1 M substrate to minimize reactions such as epoxide opening. Catalytic reactions can be run at concentrations of 1 M although Sharpless recommends substrate concentrations of 0.3-0.5 M32-42. 

Catalytic Ring-Opening and Ring Transformations of Epoxides 10.2.3.1 Achiral Catalysts... 

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 catalytic asymmetric synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine was developed by J. Lee et al. using an intramolecular epoxide opening 5-exo-tet) followed by ring expansion. The acyclic c/s-epoxide substrate was prepared in good yield and in greater than 94% ee by the Jacobsen epoxidation from the corresponding (Z)-alkene. ... 

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