843614-79-9Relevant academic research and scientific papers
Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthryl) propionic acids by an effective combination of radical and organometallic chemistry
Ricci, Giacomo,Ruzziconi, Renzo
, p. 611 - 623 (2007/10/03)
(Chemical Equation Presented) Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthr-1-yl)- and 2-(phenanthr-2-yl)-propionic acids 1-5 were prepared using phenanthren-1(2H)-ones 6a - c as key intermediates. Thus, ethyl 2-(fluorophenanthryl)propionates 11 were obtained in good yields by Reformatsky reaction of 6a - c with ethyl 2-bromopropionate followed by dehydratation and DDQ-promoted aromatization of the resulting β-hydroxyesters. Side-chain alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 14 were obtained by bromine/lithium permutation of dihydrophenanthryl bromides 12a - c with butyllithium followed by quenching of the lithiated intermediates with methyl pyruvate or ethyl 3,3,3-trifluoropyruvate and subsequent DDQ-promoted aromatization. The alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 25 were prepared by reacting 8-bromo-1,3-difluorophenanthrene 24 with butyllithium for 10 seconds at -110°C and subsequent addition of the suitable pyruvate to the lithiated intermediates. Alkyl 2-hydroxy-2-(phenanthr-2-yl)propionates 26 and 29 were suitably obtained by site-selective metalation of 1,3- difluorophenanthrene 28 and the bromophenanthrene 24, respectively, with LDA followed by quenching of the metalated intermediates with the suitable alkyl pyruvate. Fluorination of the above α-hydroxypropionates with DAST, followed by the alkaline hydrolysis, allowed the expected 2-(phenanthryl) propionic acids 1-5 to be obtained in satisfactory overall yields.
