Cyanohydrins carbonyl group protection

Carbonyl group protection. A C ==0 cyanohydrin carbonate at room tempcrati ketones are less reactive. The adducts are rr in MeOH. 

The carbonyl group forms a number of other very stable derivatives. They are less used as protective groups because of the greater difficulty involved in their removal. Such derivatives include cyanohydrins, hydrazones, imines, oximes, and semicarbazones. Enol ethers are used to protect one carbonyl group in a 1,2- or 1,3-dicarbonyl compound. 

The cyclobutane ring was then cleaved by hydrolysis of the enamine and ring opening of the resulting (3-diketone. The relative configuration of the chiral centers is unaffected by subsequent transformations, so the overall sequence is stereoselective. Another key step in this synthesis is Step D, which corresponds to the transformation 10-IIa => 10-la in the retrosynthesis. A protected cyanohydrin was used as a nucleophilic acyl anion equivalent in this step. The final steps of the synthesis in Scheme 13.11 employed the C(2) carbonyl group to introduce the carboxy group and the C(l)-C(2) double bond. 

Anions of protected cyanohydrins of aliphatic, aromatic or a,3-unsaturated aldehydes undergo 1,4-addition to cyclic and acyclic enones. The synthetic utility of protected cyanohydrins in 1,4-addition depends on regioselectivity, since a competing reaction is 1,2-addition to Ae carbonyl group. The regioselectivity of these reactions (1,4- versus 1,2-addition) is dependent on the structure of the protected cyanohydrin, the enone and the reaction solvent. Some general principles which influence die regioselectivity can be defined. 

Silylated cyanohydrins have found considerable utility in the regioselective protection of p-qui-nones, as intermediates for the preparation of 3-amino alcohols and as precursors to acyl anion equivalents. Such compounds are typicdly prepared in high yield by either thermal or Lewis acid catalyzed addition of TMS-CN across the carbonyl group. This cyanosilylation has a variety of disadvantages and modified one-pot cyanosilylation procedures have been reported. - The carbonyl group can be regenerated by treatment with acid, silver fluoride or triethylaluminum hydrofluoride followed by base. ... 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

The alkylation of protected cyanohydrin anions constitutes an excellent method for ketone synthesis. Generally the anions are generated from aliphatic or aromatic aldehyde protected cyanohyd with LDA under nitrogen at -78 C. The addition of an alkyl halide produces the protected ketone cyanohydrin. The carbonyl group is then liberated by successive treatment with dilute acid and dilute aqueous base. This method is applicable for the synthesis of buflomedil. ... 

Acyl Anions Derived from (9-Protected cyanohydrins contain a masked carbonyl group with inverted polarity. 

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