Hydroxy-ethers, from epoxides

Recent advances in the synthesis of trans-iused polycyclic ethers by hydroxy epoxide cyclization reactions via monocyclic epoxonium ion intermediates and ether ring expansion reactions via bicyclic epoxonium ion intermediates are described in a review by Fujiwara and Murai. Natural trans-iu eA polycyclic ethers (e.g., brevetoxin A and ciguatoxin), produced by marine sources such as dinoflagellates, are hypothesized to be constructed from the corresponding polyepoxide precursors by a cascade of ring-closure reactions, which has prompted much work in the development of new methods for the construction of cyclic ethers from epoxides <2004BCJ2129>. 

Openings of mcso-epoxides to obtain chiral P-hydroxy nitrile derivatives and of A -acylaziridines to afford A-(P-sulfenylalkyl) amides have enlisted the service of ligand 23 and dicyclohexyl L-(+)-tartrate, respectively. An efficient method for acquiring chiral azido silyl ethers from epoxides and Me SiN, employs a (salenlCr-N, complex 24. "... 

The results from our work on the reaction of propylene oxide with cobalt carbonyl and base in methanol are given in Table VIII. Several base/metal oxide combinations were evaluated under mild reaction conditions. The difference in activity between the bases was not as pronounced as that observed in the reaction with benzyl halides with the exception of potassium methoxide which, when used alone, gave exclusively the hydroxy ether resulting from methoxide addition to the epoxide ring. However, the activity of sodium... 

R" may be alkyl or aryl. For dialkyl ethers, the reaction does not end as indicated above, since R OH is rapidly converted to R OR by the sulfonic acid (reaction 0-16), which in turn is further cleaved to R 0S02R" so that the product is a mixture of the two sulfonates. For aryl alkyl ethers, cleavage always takes place to give the phenol, which is not converted to the aryl ether under these conditions. Ethers can also be cleaved in a similar manner by mixed anhydrides of sulfonic and carboxylic acids733 (prepared as in 0-33). p-Hydroxy alkyl perchlorates734 and sulfonates can be obtained from epoxides.735 Epoxides and oxetanes give dinitrates when treated with N2Os,736 e.g.,... 

In the case of nonsymmetrical epoxides, the regioselectivity is determined by the particular reaction conditions. Thus, styrene oxide (6) undergoes methanolysis in the presence of the Lewis acid catalyst copper(II) tetrafluoroborate to give the hydroxy ether 60, derived from attack of the nucleophile at the more substituted oxiranyl carbon. Similar outcomes have been observed in the solvolysis of 6 with the assistance of aminopropyl silica gel (APSG) supported iodine in catalytic quantities <02SL1251>. This selectivity appears to be much less decisive, however, in the case of monoalkyl epoxides, as illustrated in the corresponding reaction of 1-octene oxide (61), which yields an almost 1 1-mixture of isomers under the same conditions <02OL2817>. 

Treatment of pristinamycin IIa with meta-chloroperbenzoic acid afforded a compound to which the structure (79) was initially assigned, resulting from epoxidation of the more substituted double bond (12,13-C). This material did not display chemical properties characteristic of an epoxide as the assumed epoxide moiety remaining after treatment with nucleophilic reagents. Michael-type addition products on the dehydroproline ring were observed after treatment with thiols or amines (see Sect. 5.4.5). 2D-NMR analysis of the product from reaction of pristinamycin IIa with mCPBA showed that a transannular oxidative cyclization had taken place leading to formation of (80). The reaction can be considered to involve initial epoxidation of the 12,13-double bond followed by an intramolecular nucleophilic attack by the 37-hydroxy of the enol ether (Scheme 19). A similar transannular oxidative cyclization reaction has been reported for the reaction of l,5-dimethylcyclooct-4-en-l-ol with meta-chloroperbenzoic acid [125]. 

A stereoselective approach to tetrasubstituted (ii)-/ -hydroxy silyl enol ethers from aryl-substituted oxiranyl anions and acylsilanes is reported to occur via a sequential addition - [l,2]-Brook rearrangement - epoxide-opening (Scheme 87). ... 

It is known that trimethylsilyl ethers of p-hydroxy-nitriles may be obtained from epoxides and MesSiCN in the presence of AICI3 or Et2AlCl. It has now been shown that if zinc iodide is used in place of the aluminium reagent, iso-cyanides are obtained, e.g. (269) and (270). This transformation is highly... 

Benzyloxy-2-methylpropane-l,2-diol, a desymmetrized form of 2-methylpropane-1,2,3-triol with its terminal hydroxy being protected as a benzyl ether, was prepared using the B. subtilis epoxide hydrolase-catalyzed enantioselective hydrolysis of the racemic benzyloxymethyl-l-methyloxirane readily available from methallyl chloride and benzyl alcohol. The preparation of the racemic epoxide, a key intermediate, was described in Procedures 1 and 2 (Sections 5.6.1 and 5.6.2), its overall yield being 78 %. The combined yield of enantiomerically pure (7 )-3-benzyloxy-2-methylpropane-l,2-diol was 74 % from ( )-benzyloxymethyl-l-methyloxirane, as described in Procedures 3-5 (Sections 5.6.3 and 5.6.5), with the overall procedures leading to the biocatalytic dihydroxylation of benzyl methallyl ether . 

Z)-awh-4-Hydroxy-l-aIkenyl carbamates 363, when subjected to substrate-directed, vanadyl-catalysed epoxidation , lead to diastereomerically pure epoxides of type 364 (equation 99)247,252,269 qqjggg epoxides are highly reactive in the presence of Lewis or Brpnsted acids to form -hydroxylactol ethers 366 in some cases the intermediate lactol carbamates 365 could be isolated . However, most epoxides 364 survive purification by silica gel chromatography . The asymmetric homoaldol reaction, coupled with directed epoxidation, and solvolysis rapidly leads to high stereochemical complexity. Some examples are collected in equation 99. The furanosides 368 and 370, readily available from (/f)-0-benzyl lactaldehyde via the corresponding enol carbamates 367 and 369, respectively, have been employed in a short synthesis of the key intermediates of the Kinoshita rifamycin S synthesis . 1,5-Dienyl carbamates such as 371, obtained from 2-substituted enals, provide a facile access to branched carbohydrate analogues . 

Aromatic Compounds.—A number of 2,3-dihydroxyoestra-l,3,5(10)-trienes have been prepared from the corresponding 2-amino-3-hydroxy-compounds using a novel inverse oxidation procedure followed by reduction with KI. Addition of the substrate to sodium metaperiodate in high dilution ensures no coupling with the intermediate quinonimines. 2-Bromo-oestradiol was readily converted into 2-methoxyoestradiol by treatment with NaOMe-MeOH-DMF-CuI. Novel preparations of the biologically interesting 11/3-methyl- and 11/3-ethyl-oestradiol have been reported in full. The key intermediates were the 11-oxo-oestradiol 3-benzyl ether (82) and its 9/3-epimer (83). The latter was derived from the 9,H-epoxides (81) by treatment with KOH followed by benzylation. The thermodynamically unstable 9a-epimer (82) was prepared from the 9j8-epimer (83) by... 

It should finally be pointed out that the mild reaction conditions typically employed in dioxirane-mediated oxidations enable the asymmetric epoxidation of enol ethers and enol esters. With the silyl ethers, work-up provides enantiomeri-cally enriched a-hydroxy ketones. As summarized in Table 10.1, quite significant enantiomeric excesses were achieved by use of catalyst 10 at loadings ranging from 30 [30] to 300 mol% [31]. Enol esters afford the intact acyloxyepoxides enantiomeric purities are, again, quite remarkable. 

A mixture consisting of 3 g of l-(3-amino-3,3-dimethyl-n-propyl) benzimidazolidinone-2, 3.3 g of l-[naphthyl-(l)-oxyl]propylene-(2,3)-epoxide and 12 ml of 98% ethanol were refluxed for three hours. Thereafter, the ethanol was distilled off, the residue was taken up in some methanol, and the solution was acidified with 1 N hydrochloric acid and then extracted with ethyl acetate. The ethyl acetate was distilled out of the extract solution, and ether and some water were added to the residue, whereupon a crystalline substance separated out. The product was recrystallized from ethanol, yielding 60% of theory of ()-l-(3-((2-hydroxy-3-(l-naphthyloxy)propyl)amino)-3-methylbutyl)-2-benzimidazolinone, which had a melting point of 161°C. 

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