Cyanohydrin ethers rearrangement

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. 

An interesting development in the lithiated cyanohydrin ether approach to acyl carbanion equivalents involves the [2,3] sigmatropic rearrangement of the anions derived from allyl- or propargyl-cyanohydrin ethers/ Scheme 2 shows an example of the application of this process in the synthesis of y-dicarbonyl compounds or their monoenol ethers. ... 

If X in Scheme 41 represents a cyanide group (X = CN) the rearrangement of the anion leads to a cyanohydrin anion as the product, which can yield a carbonyl function directly.The reaction is not only known for allylic ethers but also for propargylic ethers, giving access to allenic carbonyl compounds in the latter case (equation 39). ... 

Allenic products ate formed in the anion-initiated rearrangement of cyanohydrin propargylic ethers (148 Table 10).- The intermediate cyanohydrins (149) are converted to allenyl ketones (150) upon work-up. 

CH2 -C(OMe)NMe2 in DMF for 24 hr at 160 C.233 Hydroxyesters can be made from furfural cyanohydrin and when heated with an orthoester afford vinyl ethers that rearrange in a similar manner (Scheme 58).234 The ester substituent appears to promote the rearrangement by stabilizing the intermediate. 

It is well known that alk-2-ynones can be prepared from a copper(i) alkyne and an acyl halide. Now the troublesome metallation step can be avoided by direct reaction of the terminal alkyne with the acyl chloride in triethylamine containing copper(l) iodide and bis(triphenylphosphine)palladium(ii) chloride as catalysts. Cyanohydrins and propargyl bromides form alkynyl ethers which rearrange on treatment with lithium di-isopropylamide to form ar-allenic ketones (Scheme 59). ... 

P,7-Unsaturated ethers of cyanohydrins, on formation of lithio derivatives, undergo a 2,3-sigmatropic rearrangement to form. y-unsaturated ketones (equation 21), whereas benzylic ethers of aliphatic cyanohydrins gave o-methylaryl ketones. The method has been used to prepare 3-methyi-l-(3-methyl-2-furyl)-l-butanones, a naturally occurring Cio terpene, a-allenic ketones and enolic monoethers of 7-keto aldehydes via 2,3-sigmatropic rearrangement of tiieir respective carbanions. ... 

Explored initially by Reich,cyanide addition to acyl silanes can produce Brook rearrangement, leading to an additional cascade of steps in appropriately designed systems. For example, Takeda, using a crown ether as a phase transfer agent but under non-aqueous conditions, showed that cyanide addition to acyl silanes and subsequent Brook rearrangement led, in the case of y bromo acyl silane 59 to intramolecular alkylation and formation of cyclopropanone cyanohydrin derivative 60. ... 

Johnson s group developed a catalytic asymmetric cyanation/1,2-Brook rearrangement/C-acylation of acylsilanes with cyanoformates (Scheme 19.14). In the presence of (i ,/ )-(salen)Al 19, the corresponding cyanohydrin trimethylsilyl ethers of a-keto esters were obtained in moderate to good enantioselectivities (61-82% enantiomeric excess). Access to chiral (silyloxy)nitrile anions is facilitated by metal cyanide-promoted Brook rearrangement reaction of acylsilanes. 

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