Synthesis of (1R,cis,αS)-cypermethrine via lipase catalyzed kinetic resolution of racemic m-phenoxybenzaldehyde cyanohydrin acetate

Pyrethroid insecticides. Chapter III: Synthesis of 3-phenoxy mandelonitrile

“…26,27,60 Ester hydrolysis in acidic media proved unsatisfactory because hydrolysis of the cyano group takes place faster than that of the ester. 60 Best results have been obtained performing a transesterification using lipases and an alcohol 27,55,56 such as ethanol in large excess, which is able to deprotect 1c to produce smoothly 3-phenoxymandelonitrile (S)-(3a) (Scheme 16, third step). 27 The process is highly stereoselective and therefore only applies to a single enantiomer of the racemate.…”

CAL-B Catalyzed Enantioselective Synthesis of Cyanohydrins - A Facile Route to Versatile Building Blocks

“…[1][2][3][4] However, up to now, no general and stereoselective chemical synthesis is available. [1][2][3][4] However, up to now, no general and stereoselective chemical synthesis is available.…”

“…[1][2][3][4] However, up to now, no general and stereoselective chemical synthesis is available. While there are excellent lipases for the synthesis of the industrially relevant (S)-m-phenoxybenzaldehyde cyanohydrin (4b), 3,4,14 no general or straightforward lipase catalyzed formation of cyanohydrins is available. While there are excellent lipases for the synthesis of the industrially relevant (S)-m-phenoxybenzaldehyde cyanohydrin (4b), 3,4,14 no general or straightforward lipase catalyzed formation of cyanohydrins is available.…”

“…As expected, the reaction proceeded considerably faster when the temperature was increased. 3,4,22 Alternatively, the unprotected cyanohydrin can be acylated in the mixture with the remaining acetate and then separated. The temperature was not increased above 60 ∞C, since CAL-B is known to be unstable at higher temperatures.…”

“…However, this was not coupled with a significant loss of activity or selectivity. 4 It is also possible to invert the cyanohydrin via a Mitsunobu reaction, 23 ensuring a high yield of the desired enantiomer, R or S. 15 Increasing the concentration of propanol above a ratio of 2 equiv of alcohol to 1 equiv racemic substrate showed little effect, while a concentration of 0.1 mol/l of substrate in toluene was ideal.…”