Cyclohexane carbaldehyde derivative

Scheme 9.42 Ring expansion of cyclohexane carbaldehyde derivatives.

The search for other amino acid-based catalysts for asymmetric hydrocyanation identified the imidazolidinedione (hydantoin) 3 [49] and the e-caprolactam 4 [21]. Ten different substituents on the imide nitrogen atom of 3 were examined in the preparation, from 3-phenoxybenzaldehyde, of (S)-2-hydroxy-2-(3-phenoxy-phenyl)acetonitrile, an important building block for optically active pyrethroid insecticides. The N-benzyl imide 3 finally proved best, affording the desired cyanohydrin almost quantitatively, albeit with only 37% enantiomeric excess [49]. Interestingly, the catalyst 3 is active only when dissolved homogeneously in the reaction medium (as opposed to the heterogeneous catalyst 1) [49]. With the lysine derivative 4 the cyanohydrin of cyclohexane carbaldehyde was obtained with an enantiomeric excess of 65% by use of acetone cyanohydrin as the cyanide source [21]. 

These reductions can be combined with other transformations as exemplified by cyclopropane 120, which has been converted to the nitrile 122, the spiro lactone 123, and the functionalized spiro tetrahydrofuran 121 61). All products are eventually derived from cyclohexane carbaldehyde. 

The efficiency of this approach is seen in a prompt reductive coupling of sulfide 204 with cyclohexane carbaldehyde to afford C-glycosyl derivative 205. This was applied to a fast synthesis of the same disaccharidic component of the sialylTn antigen [96] (O Scheme 43). 

This reaction is restricted to derivatives of N-benzylideneaniline since cyclohexane carbaldehyde or pivaldehyde with aniline give the product in less than 10% yield. More surprisingly, the reaction of acylzirconocene chloride 38 with imine proceeds with a Bronsted acid, even in aqueous media. Although, the hydrolysis of acylzirconocene into aldehyde is a well-known process (see Scheme 12.22), the reaction with N-phenyl imine is much faster. Under 20mol% HCl/THF, the... 

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