Hydroxy-nitriles, from epoxides

Cross-coupling reactions of ArCOAr. Reaction of Yb(0) with diaryl ketones changes the reactivity of the carbonyl group from electrophilic to nucleophilic. Thus in the presence of this lanthanoid metal, diaryl ketones couple with other ketones, nitriles, and epoxides to give pinacols, a-hydroxy ketones, and 1,3-diols, respectively, via the intermediate a. 

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. "... 

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... 

Obviously, this pathway will be more favored when the epoxide carbon further away from the nitrile group is the more substituted one.8 9 This can be demonstrated by treatment of the 5,6-epoxy-6-methylheptanenitrile with potassium hexamethyldisilazanidc in refluxing benzene to give /nmv-2-( 1-hydroxy-1 -inethylethyl)cyclobutanecarbonitrile in 70% yield (Table 14).8... 

As key intermediate for the introduction of chirality in positions 3 and 6 of 133, hydroxy-2,6,6-trimethylhex-2-en-l-one 19 was chosen this is readily available from the hydroxyketone (18) [24]. Reaction of 18 with mesyl chloride gave the corresponding mesylate which, on treatment with tetrabutylammonium acetate, was converted into the acetoxyketone 20 with complete inversion of configuration. The introduction of the second chiral centre was achieved by diastereoselective epoxidation of the protected hydroxyketone 27 with dimethyl sulphonium methylide, yielding the crystalline epoxide 22. This was readily transformed into the protected hydroxy-a-cyclocitral (23). Subsequent chain lengthening by a Horner-Emmons reaction gave a nitrile which, on treatment with MeLi, was converted into the crystalline C 13-hydroxy ketone 24 in excellent optical yield. The compounds mentioned were identified by m.p, [a] , IR, H-NMR, X-ray, CD and MS [24],... 

Silyl cyanides react enantioselectively with such electrophiles as aldehydes, ketones, imines, activated azines, or,/ unsaturated carbonyl compounds, epoxides, and aziridines in the presence of chiral Lewis acid catalysts to give functionalized nitriles, versatile synthetic intermediates for hydroxy carboxylic acids, amino acids, and amino alcohols (Tables 3-6, 3-7, 3-8, and 3-9, Figures 3-6, 3-7, and 3-8, and Scheme 3-154). ° Soft Lewis acid catalytst, the reaction of epoxides with trimethylsilyl cyanide often leads to isonitriles, which are derived from silylisonitrile spiecies (Schemes 3-155 and 3-156). Soft Lewis base such as phosphine oxide also catalyzes the reaction and cyanohydrin silyl ethers of high ee s are isolated. 

Miscelleneous Applications. The method of choice for the regioselective opening of benzylic and tertiary epoxides with alcohols (eq 13) appears to be a reaction mediated by organ-otin phosphate condensate (OPC) , which is readily prepared from DBTO and tributyl phosphate. DBTO catalyzes rearrangement of 3-hydroxy-2-oxo carboxylic acid esters (eq 14), a reaction reminiscent of a similar one mediated by the enzyme reductoisomerase. DBTO has been used as a catalyst for the addition of Azidotrimethylsilane to nitriles for the production of tetrazoles (eq 15). 

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