Epoxide opening, thiol

The enantioselective ring opening of mew-epoxides with thiols can also be facilitated by chiral (salen)Ti(IV) complex.43 As shown in Scheme 4-25, in the presence of salen compound 71 and Ti(OPr )4, ring opening of mew-epoxide proceeds at —25° to —40°C, giving a product with good chemical yield and moderate ee. 

When the epoxide is 1,2-disubstituted, steric and electronic effects are responsible for the preferential formation of one product. In this context, benzyl radicals are always produced irrespective of the substitution pattern of the epoxide. For these intermediates, the more reactive tert-butyl thiol is the hydrogen atom donor of choice. Chelation of titanium can be used to good effect for regioselective epoxide opening, as shown in Scheme 12.8 [5d]. 

Wu, M. H. Jacobsen, E. N. (1998) Asymmetric ring opening of meso-epoxides with thiols enantiomeric enrichment using a bifunctional nucleophile., J. Org. Chem., 63 5252-5254. 

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 other side of the coin is specific base catalysis (SBC) which usually involves the removal of a proton from the substrate in a fast pre-equilibrium step followed by a rate-determining reaction of the anion. Most of the base-catalysed reactions you are familiar with work by SBC. Examples include opening of epoxides with thiols. 

The ring opening of epoxides with thiols provides an efficient route for the formation of (3-hydroxy sulfides. A one-pot method for the direct synthesis of (3-hydroxy sulfoxides has been developed <07JOC4524>. Treatment of an epoxide with PhSH, Ga(O IT)3, and H202 directly provides the sulfoxide with little to no over oxidation. 

Heterogenous metal tartrates were screened for their efficacy in the catalysis of the asymmetric ring opening of me o-2,3-disubstituted epoxides with thiols, aniline, and trimethylsilyl azide [72]. Whereas the enantioselectivity of Zn(II) tartrates is in the 15-85 % ee range, selectivity with the Mn(II), Fe(II), and Co(II) tartrates was lower (< 40 % ee). With Nugent s Zr(Of-Bu)4/C3-symmetric tetradentate ligand catalyst... 

Mechanistic studies of the opening of the epoxide point to catalyst activation of both nucleophile and electrophile in a bimetallic array [79]. The Cr complex results in moderate ee only when used with thiol nucleophiles but enhancement is feasible by using a dithiol in a two-step selection process [80]. Enantioselective epoxide opening with carboxylic acids is more efficient with (salen)Co(III) complexes (often obtained via in situ oxidation of the Co(II) complex) than with the Cr analogs (Table 6, entries 4 and 5) [81]. This methodology was successfully extended to intramolecular desym-metrization of meso epoxy alcohols [82]. 

Lanthanide Lewis acids catalyze many of the reactions catalyzed by other Lewis acids, for example, the Mukaiyama-aldol reaction [14], Diels-Alder reactions [15], epoxide opening by TMSCN and thiols [14,10], and the cyanosilylation of aldehydes and ketones [17]. For most of these reactions, however, lanthanide Lewis acids have no advantages over other Lewis acids. The enantioselective hetero Diels-Alder reactions reported by Danishefsky et al. exploited one of the characteristic properties of lanthanides—mild Lewis acidity. This mildness enables the use of substrates unstable to common Lewis acids, for example Danishefsky s diene. It was recently reported by Shull and Koreeda that Eu(fod)3 catalyzed the allylic 1,3-transposition of methoxyace-tates (Table 7) [18]. This rearrangement did not proceed with acetates or benzoates, and seemed selective to a-alkoxyacetates. This suggested that the methoxy group could act as an additional coordination site for the Eu catalyst, and that this stabilized the complex of the Eu catalyst and the ester. The reaction proceeded even when the substrate contained an alkynyl group (entry 7), or when proximal alkenyl carbons of the allylic acetate were fully substituted (entries 10, 11 and 13). In these cases, the Pd(II) catalyzed allylic 1,3-transposition of allylic acetates was not efficient. 

Brill and co-workers used levoglucosane as a rigid scaffold to synthesise libraries both in solution [74] and solid phase [75]. The opening of epoxide 125 by different hydroxycarboxylic acid methyl esters catalysed by Lewis acid, followed by simultaneous new epoxide formation and ester hydrolysis gave the resulting free acid ready for attachment to the solid support. Epoxide opening reactions with alkoxides, amines and thiols were carried out on solid phase... 

Ring opening of 1,2-epoxides with thiol-derived nucleophiles is a well established route to /3-hydroxy sulfides that has been applied for the preparation of allylic alcohols, cyclic sulfides, thioketones, and important intermediates for the synthesis of... 

Chapter 18—Ethers and Epoxides Thiols and Sulfides. Coverage of the Claisen rearrangement has been expanded, and a biological example of the reaction has been added in Section 18.4. Epoxide opening by amine nucleophiles has been added to Section 18.6. 

Gallium triflate also catalyzes ring opening of epoxides by thiols with high regioselectivety and chemoselectivity. The reaction is highly catalytic (only 1 mol % gallium triflate is required) and occurs under solvent-free conditions (eqs 12 and 13). ... 

SCHEME 5.12 Ring opening of epoxides with thiol ate anions [13]. 

Epoxide Opening. LiC104 is an efficient promotor for the regioselective nucleophilic opening of oxiranes with amines, cyanide, azide, thiols, halides, and lithium acetylides. The regioselective opening of oxiranes with lithium enolates derived from ketones has also been observed in the presence of LiC104 (eq 6). ... 

One of the earliest useful methods for asymmetric opening of meso-epoxides with sulfur-centered nucleophiles was reported by Yamashita and Mukaiyama, who employed a heterogeneous zinc tartrate catalyst (Scheme 7.10) [20]. Epoxides other than cydohexene oxide were not investigated, and the enantioselectivity depended strongly on the identity of the thiol. 

The enantioselectivity was significantly influenced by the steric factor of the thiols employed. When p-MeC6H4SH and PhSH were used, the optical yields decreased to 69% and 3%, respectively. Shibasaki et al. have reported that gallium-lithium-bi-naphthoxide (GLB) 51 became a good catalyst for the enantioselective ring opening reaction of epoxide for the production of 52 (Eq. 7.39) [46]. 

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