Epoxidation guanidines

Novel supported guanidine catalysts, based on 1,1,3,3-tetramethylguanidine have been prepared using a variety of synthetic routes. The catalysts have been shown to be efficient catalysts for the base-catalysed epoxidation of electron-deficient alkenes, and show promise in the Linstead variation of the Knoevenagel condensation. 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

A chiral, nonracemic oxirane, (3 )-2-[(R)-fluoro(phenyl)methyl]oxirane, can react with (chiral) amines under the influence of lithium perchlorate using either heat or microwave irradiation. This reaction sequence provides a material from which the ee of chiral a-branched amines can be determined <2005OL3829>. Guanidines serve as a useful nitrogen nucleophile for the direct conversion of epoxides to aziridines <2004JOC8504>. 

Guanidines are useful nucleophiles in the intramolecular ring opening of epoxides <2003TL3075>. The intramolecular addition of an amide anion to an oxirane in a 6-o o-fashion formed 2-ketopiperazine derivatives <20040L4069>. This reaction type was also used in a recent quinine synthesis <2004TL3783>. 

Amidines (and guanidines) react with a-cyanoepoxides (13) to give 4 amino-5-carbethoxy-, 5-cyano-4-hydroxy- and 4-carbethoxy-5-phenylimida-zoles, depending on the reaction medium, and on the degree of steric hindrance in the epoxides (Scheme 4.3.6). If =H in the epoxide, mixtures of products are obtained. With added triethylamine an imidazoline is isolated, but it can be aromatized by heating in the presence of acetic acid. Although these reactions are reasonably chemoselective, the exotic natures of the starting materials reduce the appeal of the method somewhat [32]. 

Knoevenagel reactions and epoxidation of enones were achieved by using silica-gel immobilized guanidines. 3-Nonenoic acid, which is precursor of y-nonanoic lactone, was produced from malonic acid and heptanal in the presence of silica-gel bound 1,1,3,3-tetramethylguanidine [25], This catalyst and MCM-TBD catalyzed the epoxidation of enones in the presence of H202. MCM-TBD has been prepared from MCM-41 covered with 3-trimethoxylsilylpropoxymethyloxirane and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) by Jacobs et al. [26] (Scheme 5.9). 

Supported guanidines are prepared via different routes, and their activity compared in two reactions of interest. The base-catalysed epoxidation of electron-deficient alkenes is described, and proceeds with excellent conversions and selectivities, when the surface is passivated by silylation. The Linstead variation of the Knoevenagel condensation is also described, and gives excellent conversions to partially decarboxylated products. 

Novel guanidine bases supported on silicas and micelle-templated silicas have been prepared and investigated in the base-catalysed epoxidation of election-deficient alkenes. 

Excellent conversions and selectivities were observed both with respect to the alkene and the primary oxidant [62]. In nitro-Michael reaction it was noted that the Murphy s PTC does not work as a good chiral catalyst for the Michael reaction of chalcone, but the same PTC effectively catalyses the epoxidation of chalcones with sodium hypochlorite (NaOCl) [24c]. Trials for the epoxidation of chalcone in the combination of hydroperoxides and modified guanidines 19 [27b] resulted in less effective asymmetric induction compared to the Murphy s PTC [53] (Scheme 4.21). 

Kumamoto, T., Rhine, K., Endo, M. et al. (2005) Guanidine-catalysed asymmetric addition reactions Michael reaction of cyclopentenone with dibenzyl malonates and epoxidation of chalcone. Heterocycles, 66, 347-359. 

Blanc, A.C., Macquarrie, D.J., Valle, S. et al. (2000) The preparation and use of novel immobilized guanidine catalysts in base-catalysed epoxidation and condensation reactions. 

Genki et al. reported the epoxidation reaction of dienone using a combination of tert-butyl-hydroperoxide and a guanidine base [56]. Applying this methodology, they achieved a synthesis of ( )-preussomerin L (188) [56]. Reaction of dienone 186 with ferf-butyl hydroperoxide and TBD in toluene gave bis-a,(3-epoxyketone 187 in 91% yield. The ketone 187 was efficiently led to the natural product 188 (Scheme 7.42). 

These bases have in recent years been utilized as stoichiometric bases in Wittig reactions [23], in Horner-Wadsworth olefinations [23] and in the synthesis of etioporphyrin from protoporphyrin [24]. Guanidines are useful as catalysts in, for example, the selective synthesis of monoglycerides [25], enone epoxidation... 

Treatment of epoxide (76) with isopropylamine affords the expected amino alcohol (Equation (20)) <85MI 924-04>. Other side-chain functionalities also display typical chemical reactions thus, (77 X = OH) is esterified by 3,4,5-trimethoxybenzoyl chloride <84MIP121838>, and iV-chloroethyl derivative (77 X = C1) undergoes nucleophilic displacement by guanidine, affording (77 X = NHC(NH)NH2) <84MI924-01>. 

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