O-acyl-cyanohydrins

Effenberger and coworkers have utilized the tolerance of methyl ketones by the recombinant enzyme to develop an alternative synthesis of tetronic acids and their amino derivatives, as shown in Figure 5.18. Treatment of O-acyl cyanohydrins with lithium disilazide resulted in base-induced ring closure to amino tetronic acid derivatives. Alternatively, the cyanohydrins could be converted to a-hydroxy esters prior to acylation, and the same base-induced cyclization then led to tetronic acid derivatives [89]. 

DBU catalyses cyanoacylation of ketones, R OR2, with aromatic acyl cyanides giving O-acyl cyanohydrin adducts, ArOCO-C(CN)R1R2, in fair to good yields in 2 h at ambient temperature.256... 

Thus, the O-acylated cyanohydrins 81 are cyclized in the presence of perchloric acid to 2-oxazolin-4-onium salts 82, which are then deprotonated to the corresponding 2-oxazolin-4-ones 8368,69 (equation 30). 

Enantiomerically enriched O-trimethylsilyl cyanohydrins were transformed directly into O-acyl-cyanohydrins using various anhydrides or acid chlorides in the presence of a catalytic amount of Sc(OTf)3 (Scheme 12.40) [94]. 

In addition, Moberg et al. have reported a synthesis of enantioenriched O-acylated cyanohydrins cooperatively catalysed by a chiral titanium complex and an achiral base such as TEA. The reaction occurred between acyl cyanides and prochiral aldehydes in dichloromethane at —40 °C, providing the corresponding O-acylated cyanohydrins in good to high yields (64-93%) and moderate to high enantioselectivities ranging from 20 to 96% ee. As shown in Scheme 7.17, it was supposed that the Lewis acid was able to activate both the acyl cyanide and the aldehyde whieh was verified by NMR spectroseopy, and the Lewis base simultaneously served to liberate the... 

Scheme 7 Chirality transfer in unsaturated O acyl cyanohydrins.

Lithiated O-silyl cyanohydrins add to cyclobutenediones to form acyl cyclobutenone intermediates 634, which can undergo ring expansion to provide 2/7-pyran-2-ones (Scheme 144) <1999JOC2145>. 

In 1971 Stork and Maldonado showed that anions derived from O-protected cyanohydrins of aldehydes could be efficiently metallated and the resultant anions could serve as synthetically useful acyl anion equivalents. Other develop-... 

Carbonyl Umpolung. When deprotonated with a strong base, O-(trimethylsilyl) cyanohydrins can function as effective acyl anion equivalents that can be used to convert aldehydes to ketones, and in the synthesis of 1,4-diketones, tricyclic ketones, and the highly sensitive a, -epoxy ketone functionality (eq 18). ... 

The combination of ortho metallation and meta nucleophilic acylation was used to prepare a key intermediate in a synthesis of deoxyfrenolicin (42), as outlined in Scheme 11. The complex of anisole is orf/io-metallated with n-butyllithium and quenched with chlorotrimethylsilane the resulting [(o-(tri-methylsilyl)anisole)Cr(CO)3] (43) is then metallated again, converted to the arylcuprate, and coupled with ( )-2-hexenyl bromide to give the complex of l-trimethylsilyl-2-methoxy-3-(2-hexenyl)benzene (44). Addition of the carbanion from the cyanohydrin acetal of 4-pentenal, followed by the standard iodine oxidation and subsequent hydrolysis of the cyanohydrin acetal to regenerate the carbonyl group... 

While the addition/oxidation and the addition/protonation procedures are successful with ester enolates as well as more reactive carbon nucleophiles, the addition/acylation procedure requires more reactive anions and the addition of a polar aprotic solvent (HMPA has been used) to disfavor reversal of anion addition. Under these conditions, cyano-stabilized anions and ester enolates fail (simple alkylation of the carbanion), but cyanohydrin acetal anions are successful. The addition of a cyanohydrin acetal anion to l,4-dimethoxynaphthalene-Cr(CO)3 occnrs by kinetic control at C-/3 in THF/HMPA and leads to the O -diacetyl derivative after methyl iodide addition and hydrolysis of the cyanohydrin acetal. Monoacylation of 1,4-dimethoxynaphthalene-Cr(CO)3 has been achieved nsing the seqnence of reactions shown in eqnation (126). ... 

Oxidation of a cyanohydrin derived from a conjugated aldehyde (as the O-TMS derivative) using py-ridinium dichromate (PDC) in DMF gave an a,p-unsaturated lactone (6 -butenolide) as the major product (equation 12). Simple nonconjugated cyanohydrins are not satisfactory substrates for the synthesis of acyl cyanides using PDC, because they seem to add to the initially formed acyl cyanides, leading ultimately to cyanohydrin esters. Oxidation of cyanohydrin to acyl cyanides can be carried out either by means of manganese dioxide, mthenium-catalyzed oxidation with r-butyl hydroperoxide or NBS. ... 

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