Cyanohydrin ether

Cyclic cyanohydrin ethers, 6-alkyl-2,2-dimethyl-l,3-dioxane-4-carbonitriles 1, are easily available from silylated aldols. Deprotonation of 1 and subsequent alkylation gives, v+ -4,6-disubsti-tuted 2,2-dimethyl-l,3-dioxane-4-carbonitriles 2 in good yields in a highly diastereoselective reaction48. Primary bromoalkanes and oxiranes have been used as alkylating reagents. Reduction of the alkylation products 2 afforded the protected, vj. -l,3-diols 3 with complete retention of configuration (see Section D.2.I.). 

A similar method was used for the synthesis of a cyclic cyanohydrin ether 75. The cyclization took place by the intramolecular displacement of the polymer-supported cyanohydrin 74 by treatment with lithium hexa-methyldisilazide (Scheme 21). Target 75 was obtained in 46% yield. While the yield is moderate, a pure product was obtained after a simple workup procedure. The cyanohydrin ether 75 can be readily converted to a cyclic ketone.46... 

Cyanation of acetals. Reaction of acetals with t-butyl isocyanide catalyzed by TiCU results in cyanohydrin ethers in high yield. A similar reaction with ethylene acetals results in spirolactones. 

Chiral cyanohydrines The TiCU-catalyzed reaction of (CH,),SiCN with (2R,4R)-pentanediol acetals (2) gives cyanohydrin ethers (3) with high diastereoselectivity (-95% de). 

Strecker reactions are among the most efficient methods of synthesis of a-amino nitriles, useful intermediates in the synthesis of amino acids [73] and nitrogen-containing heterocycles such as thiadiazoles, imidazoles, etc. [74]. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a source of cyano anion provides promising and safer routes to these compounds [73b,75]. TMSCN is, however, readily hydrolyzed in the presence of water, and it is necessary to perform the reactions under strictly anhydrous conditions. BusSnCN [76], on the other hand, is stable in water and a potential source of cyano anion, and it has been found that Strecker-type reactions of aldehydes, amines, and BuaSnCN proceed smoothly in the presence of a catalytic amoimt of Sc(OTf)3 in water [77]. No surfactant was needed in this reaction. The reaction was assumed to proceed via imine formation and successive cyanation (it was confirmed that imine formation was much faster than cyanohydrin ether formation under these reaction conditions) again the dehydration process (imine formation) proceeded smoothly in water. 

In the presence of a Lewis acid such as SnCh, BF3 OEt2, ot TiC104, TMS-CN reacts with acetals to give cyanohydrin ethers. o-Ribofuranosyl cyanide, an important intermediate of C-nucleoside synthesis, is prepared from a furanosyl acetate (Scheme 23). ... 

In catalytic processes with enzymes such as D-oxynitrilase and (R) xynitrilase (mandelonitrilase) or synthetic peptides such as cyclo[(5)-phenylalanyl-(5)-histidyl], or in reaction with TMS-CN pro-mot by chiral titanium(IV) reagents or with lanthanide trichlorides, hydrogen cyanide adds to numerous aldehydes to form optically active cyanohydrins. The optically active Lewis acids (8) can also be used as a catalyst. Cyanation of chiral cyclic acetals with TMS-CN in the presence of titanium(IV) chloride gives cyanohydrin ethers, which on hydrolysis lead to optically active cyanohydrins. An optically active cyanohyrMn can also be prepared from racemic RR C(OH)CN by complexation with bru-... 

The condensation of cyanohydrin ethers with aldehydes or ketones provides a-hydroxy ketones. 0-Benzoyl-protected cyanohydrins react with aldehydes to give a-hydroxy ketones via intramolecular deprotective benzoylation analogous to TMS-protect cyanohydrins (Scheme 10). ... 

Allylic ethers of cyanohydrins are easily prepared through phase transfer allylation. Deprotonation of these ethers with LDA in THF at -78 °C effects 2,3-rearrangement to transient p. y-unsaturated ketone cyanohydrins, which are transformed during work-up to the ketones (Table 16). In an extension of this work, the mixed acetal cyanohydrin ethers (187), prepared by mild acid treatment of the cyanohydrins with 2-methoxy-1,3-butadiene or 1-f-butoxyallene, rearranged to the keto enol ethers (189 equation 40). Hydrolysis of the enol ethers (189) leads to 1,4-dicarbonyl compounds, which can be cyclized to cyclopentenones. 

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