187837-12-3Relevant 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
Synthesis and reactions of enantiopure substituted benzene cis-hexahydro-1,2-diols
Boyd,Sharma,Berberian,Dunne,Hardacre,Kaik,Kelly,Malone,McGregor,Stevenson
experimental part, p. 855 - 868 (2010/07/05)
Enantiopure dis-dihydro-1,2-diol metabolites, obtained from toluene dioxygenase-catalysed dis-dihydroxylation of six monosubstituted benzene substrates, have been converted to their corresponding dis-hexahydro-1,2-diol derivatives by catalytic hydrogenation via their dis-tetrahydro-1,2-diol intermediates. Optimal reaction conditions for total catalytic hydrogenation of the dis-dihydro-1,2-diols have been established using six heterogeneous catalysts. The relative and absolute configurations of the resulting benzene dis-hexahydro-1,2-diol products have been unequivocally established by X-ray crystallography and NMR spectroscopy. Methods have been developed to obtain enantiopure dis-hexahydro-1,2diol diastereoisomers, to desymmetrise a meso-cishexahydro-1,2-diol and to synthesise 2-substituted cyclohexanols. The potential of these enantiopure cyclohexanols as chiral reagents was briefly evaluated through their application in the synthesis of two enantiomerically enriched phosphine oxides from the corresponding racemic phosphine precursors.
