Reactions of nitrogen nucleophiles with enantiopure cyclohexenyl electrophiles:a stereo- and regio- selective study


Autoria(s): Boyd, Derek; Das Sharma, Narain; Belhocine, Tayeb; Malone, John F.; McGregor, Stuart T.; Atchison, Jordan; McIntyre, Peter A. B.; Stevenson, Paul J.
Data(s)

01/12/2013

Resumo

<p>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 S(N)2 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 S(N)2-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(N)2 and S(N)2 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-S(N)2 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 S(N)2 mechanism. Copyright (c) 2013 John Wiley & Sons, Ltd.</p>

Identificador

http://pure.qub.ac.uk/portal/en/publications/reactions-of-nitrogen-nucleophiles-with-enantiopure-cyclohexenyl-electrophiles(96e6bf21-55f9-4716-8a3f-f50976f0eddf).html

http://dx.doi.org/10.1002/poc.3183

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Boyd , D , Das Sharma , N , Belhocine , T , Malone , J F , McGregor , S T , Atchison , J , McIntyre , P A B & Stevenson , P J 2013 , ' Reactions of nitrogen nucleophiles with enantiopure cyclohexenyl electrophiles : a stereo- and regio- selective study ' Journal of Physical Organic Chemistry , vol 26 , no. 12 , pp. 997-1008 . DOI: 10.1002/poc.3183

Palavras-Chave #dihydrodiols #vinyl epoxides #bromoacetates #S(N)2 #sigmatropic rearrangement mechanisms #CHEMOENZYMATIC TOTAL-SYNTHESIS #ARENE OXIDATION-PRODUCT #BIASED 3,3-SIGMATROPIC REARRANGEMENT #ASYMMETRIC ALLYLIC ALKYLATION #BENZENE CIS-1,2-DIHYDRODIOLS #SUBSTITUTION-REACTIONS #INHIBITORY-ACTIVITIES #AZIDE REARRANGEMENT #EFFICIENT SYNTHESIS #BUILDING-BLOCKS
Tipo

article