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The Journal of organic chemistry

Synthesis of (+/-)-trans-7,8-Dihydrodiol of 6-Fluoro-benzo[a]pyrene via Hydroxyl-Directed Regioselective Functionalization of Substituted Pyrene.


PMID 11674280

Abstract

Synthesis of (+/-)-trans-7,8-dihydroxy-6-fluoro-7,8-dihydrobenzo[a]pyrene, the metabolite from 6-fluoro-benzo[a]pyrene, is described. Position 6 of 7,8,9,10-tetrahydrobenzo[a]pyren-7-ol (1) was functionalized by bromination with N-bromosaccharin. Regioselectivity in the bromination is thought to derive from a substrate-reagent hydrogen bond. NMR evidence is offered to support this model. The 6-bromo derivative 2 was subjected to dehydration followed by bromine-lithium exchange. Quenching the lithio intermediate with NFSi afforded the 6-fluoro derivative 4. Prévost reaction on the 7,8 double bond resulted in the trans dibenzoate 5 (established by comparison to a cis derivative prepared by osmium tetroxide cis dihydroxylation). Introduction of the 9,10 double bond by a bromination-dehydrobromination procedure, followed by hydrolysis, gave racemic trans-7,8-dihydrodiol 7. Resolution of the enantiomers was achieved by chiral HPLC, and the absolute configurations of the early and late eluting isomers were determined through CD spectroscopy by comparison with the metabolically obtained (7R,8R)-dihydrodiol.

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391611
7,8,9,10-Tetrahydrobenzo[a]pyren-7-ol, 98%
C20H16O