Chemoenzymatic synthesis of trans-dihydrodiol derivatives of monosubstituted benzenes from the corresponding cis-dihydrodiol isomers.
Enantiopure trans-dihydrodiols have been obtained by a chemoenzymatic synthesis from the corresponding cis-dihydrodiol metabolites, obtained by dioxygenase-catalysed arene cis-dihydroxylation at the 2,3-bond of monosubstituted benzene substrates. This generally applicable, seven-step synthetic route to trans-dihydrodiols involves a regioselective hydrogenation and a Mitsunobu inversion of configuration at C-2, followed by benzylic bromination and dehydrobromination steps. The method has also been extended to the synthesis of both enantiomers of the trans-dihydrodiol derivatives of toluene, through substitution of a vinyl bromine atom of the corresponding trans-dihydrodiol enantiomers derived from bromobenzene. Through incorporation of hydrogenolysis and diMTPA ester diastereoisomer resolution steps into the synthetic route, both trans-dihydrodiol enantiomers of monohalobenzenes were obtained from the cis-dihydrodiols of 4-haloiodobenzenes.
Boyd
Derek R
DR
School of Chemistry and Chemical Engineering, Queen's University Belfast, Belfast, UK BT9 5AG. dr.boyd@qub.ac.uk
Sharma
Narain D
ND
Llamas
Nuria M
NM
Coen
Gerard P
GP
McGeehin
Peter K M
PK
Allen
Christopher C R
CC
D001555:Benzene Derivatives / Q000138:chemical synthesis*; D001966:Bromine / Q000737:chemistry; D002384:Catalysis; D049308:Dioxygenases / Q000378:metabolism*; D006219:Halogens / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D006868:Hydrolysis; D007536:Isomerism; D008956:Models, Chemical; D009281:Naphthalenes / Q000737:chemistry* / Q000378:metabolism*; D014050:Toluene / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry
D001555:Benzene Derivatives; D006219:Halogens; D009281:Naphthalenes; D014753:Vinyl Compounds; C507866:trans-1,2-dihydro-1,2-naphthalenediol; D014050:Toluene; D006859:Hydrogen; C003763:vinyl bromide; D049308:Dioxygenases; D001966:Bromine