ISSN:
0947-6539
Keywords:
asymmetric synthesis
;
C—C bond formation
;
cyanohydrins
;
drug research
;
umpolung
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
We present the first cyanohydrin derivative 4 that allows diastereoselective umpolung reactions. In 4 the OH group of the cyanohydrin is linked with a chiral phosphate, which can be removed hydrolytically after asymmetric synthesis. Cyclization of pseudoephedrine 1d with POCl3 gave 2d. This was followed by addition of racemic benzaldehyde cyanohydrin 3 to give the key intermediate 4d with complete retention of the configuration at phosphorus. Deprotonation of 4d, followed by addition of a wide variety of electrophiles afforded the crystalline products 5 with high diastereomeric excesses (de up to 94%). High asymmetric induction was also achieved for the reaction of 4-Li+ with acyl halides, α-bromoacetates, 2-cycloalkenones, α,β-unsaturated esters, and γ-bromoacetates. Lewis acid assisted hydrolysis proceeded without racemization and gave high yields of ketone cyanohydrins 6. From the ring-opened chiral auxiliary 7, optically pure pseudoephedrine 1 was readily recovered by acid hydrolysis. Optically pure (R) and (S) ketone cyanohydrins are now accessible in a very general strategy, which circumvents the substrate limitations of enzymatic synthesis.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chem.19970030815
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