Synthesis of p-phenylthio- peri-hydroxy polyaromatic compounds by strong-base-induced [4+2] cycloaddition of 4- (phenylthio)homophthalic anhydrides with phenylsulfinyl- dienophiles
Kiyosei Iio, Akiko Okajima, Yoshifumi Takeda, Ken-ichi Kawaguchi, Brendan A. Whelan, Shuji Akai, and Yasuyuki Kita*
Graduate School of Pharmaceutical Sciences, Osaka University,
1-6 ,Yamada-oka, Suita, Osaka 565-0871, Japan
E-mail:
[email protected]
Dedicated to Professor Keiichiro Fukumoto on the occasion of his 70th birthday
(received 29 May 03; accepted 06 Aug 03; published on the web 11 Aug 03)
Abstract
A direct and regioselective synthesis of p-phenylthio-substituted peri-hydroxy polyaromatic compounds (9–12) was developed via the strong-base-induced [4+2] cycloaddition of the 4- (phenylthio)homophthalic anhydrides (1a–d) to the phenylsulfinyl-substituted dienophiles (5–8). The sulfinyl group in 5–8 is the key to producing the desired reaction under mild conditions (at – 20 °C to room temperature) in good yields. A reaction mechanism explaining the remarkable effect of the sulfinyl group is discussed.
Keywords: peri-Hydroxy polyaromatic compounds, strong-base-induced [4+2] cycloaddition, homophthalic anhydride, sulfinyl-substituted dienophile
Introduction
General and efficient syntheses of peri-hydroxy polyaromatic p-quinones (I) and their dihydroquinone derivatives (II) are important in recent synthetic organic- and medicinal chemistry because these compounds are key components of many biologically important natural products such as anthracyclines1 and fredericamycin A.2 For the synthesis of these quinone compounds, the transformation of phenols into p-benzoquinones or p-dihydrobenzoquinone derivatives has been one of the most important steps.3 Recently, we reported a new method for the synthesis of I and II from p-(phenylthio)phenols (III) via the aromatic Pummerer-type reaction of the derived sulfoxides (IV).4 The synthesis of III has been achieved by two methods; viz, the p-specific thiocyanation of phenols (V) using the combination of PhICl2 and Pb(SCN)2
