1498378-87-2Relevant articles and documents
Reactions of nitrogen nucleophiles with enantiopure cyclohexenyl electrophiles: A stereo- and regio- selective study
Boyd, Derek R.,Sharma, Narain D.,Belhocine, Tayeb,Malone, John F.,McGregor, Stuart T.,Atchison, Jordan,McIntyre, Peter A. B.,Stevenson, Paul J.
, p. 997 - 1008 (2014/01/06)
The reactions of enantiopure cyclohexene epoxides and trans-1,2- bromoacetates, derived from the corresponding substituted benzene cis-dihydrodiol metabolites, with nitrogen nucleophiles, were examined and possible mechanisms proposed. An initial objective was the synthesis of new 1,2-aminoalcohol enantiomers as potential chiral ligands and synthetic scaffolds for library generation. These apparently simple substitution reactions proved to be more complex than initially anticipated and were found to involve a combination of different reaction mechanisms. Allylic trans-1,2-azidohydrins were prepared by Lewis acid-catalysed ring-opening of cyclic vinyl epoxides with sodium azide via an SN2 mechanism. On heating, these trans-1,2-azidohydrins isomerized to the corresponding trans-1,4-azidohydrins via a suprafacial allyl azide [3,3]-sigmatropic rearrangement mechanism. Conversion of a 1,2-azidohydrin to a 1,2-azidoacetate moved the equilibrium position in favour of the 1,4-substitution product. Allylic trans-1,2- bromoacetates reacted with sodium azide at room temperature to give C-2 and C-4 substituted products. A clean inversion of configuration at C-2 was found, as expected, from a concerted SN2-pathway. However, substitution at C-4 was not stereoselective and resulted in mixtures of 1,4-cis and 1,4-trans products. This observation can be rationalized in terms of competitive S N2 and SN2′ reactions allied to a [3,3]-sigmatropic rearrangement. cis-1,2-Azidohydrins and cis-1,2-azidoacetates were much more prone to rearrange than the corresponding trans-isomers. Reaction of the softer tosamide nucleophile with trans-1,2-bromoacetates resulted, predominantly, in C-4 substitution via a syn-SN2′ mechanism. One application of the reaction of secondary amines with allylic cyclohexene epoxides, to give trans-1,2-aminoalcohols, is in the synthesis of the anticholinergic drug vesamicol, via an SN2 mechanism. Copyright 2013 John Wiley & Sons, Ltd. Multiple reaction pathways including SN2, S N2′, and [3,3]-sigmatropic rearrangement mechanisms are required to rationalize the formation of products obtained from the reaction of cyclohexene epoxides and trans-bromoacetates with azide and other nitrogen nucleophiles. Copyright
