An Alternative Synthetic Access to cis-4a-Methyloctahydrophenanthrene, a Biomarker of Sergipe-Alagoas Basin Petroleum in Brazil

Abstract

cis-4a-Metiloctaidrofenantreno (1) foi preparado em 8 etapas (23% rendimento total) a partir do ácido 2-bromofenilacético (3) e cicloexano-1,3-diona (6). Uma reação de acoplamento do tipo Michael Heck com alta diastereosseletividade cis foi a etapa chave na montagem do esqueleto tricíclico. O composto 1 foi utilizado como padrão cromatográfico o que permitiu identificação-inequívoca de um biomarcador minoritário presente no petróleo de Carmópolis, Bacia de SergipeAlagoas, Brasil.cis-4a-Methyloctahydrophenanthrene (1) was prepared in 8 steps (23% overall yield) from 2-bromophenyl)acetic acid (3) and cyclohexane-1,3-dione (6). A highly cis-diastereoselective Michaeltype Heck coupling served as the key step in the assembly of the tricyclic skeleton. This compound 1 was used as gas chromatography standard which allowed the unequivocal identification of a minor biomarker present in Carmopolis oil from the Sergipe-Alagoas Basin in Brazil. Keywords: cis-4a-Methyloctahydrophenanthrene, biomarker, Carmopolis petroleum, SergipeAlagoas Basin IntroductionGC/MS analyses of Brazilian petroleum 1 (Carmopolis oil field, Sergipe-Alagoas Basin, Brazil) disclosed the presence of several acids and hydrocarbons possessing alkylsubstituted monoaromatic sterane, and methyloctahydrophenanthrene (biodegraded monoaromatic sterane) skeletons, most of which require non-commercial standards for full characterization. Confirming the presence of both biomarkers, 1 and 2, possessing cis A/B-ring configuration, in the studied oils, would provide evidence for the low maturity level of the petroleum and of a common diagenetic precursor for 1 and 2 (Figure 1). 2 Preparation of cis-4a-methyloctahydrophenanthrene (1) has already been accomplished along several routes. 2 Notwithstanding these reports we proposed a new synthetic strategy assess cis-diastereomer 1 which would easily be extended to the synthesis of 2. Results and DiscussionThe most attractive synthetic strategy based on a retrosynthetic analysis called for the insertion of the arylpalladium bromide intermediate formed from the aryl bromide unit in 9 into the tethered cyclohexenone moiety (Scheme 1). This would correspond to the carbopalladation step of an intramolecular Heck reaction, one of the most versatile palladium-catalyzed carbon-carbon bond-forming processes, that has been widely applied for the construction of complex carbon skeletons, 3 and works particularly well with an electron-acceptor-substituted alkene partner. However, since the intramolecular carbopalladation in 9 generates a quaternary center, the intermediate cannot undergo β-hydride elimination, and must take the course of an overall conjugate addition, as has previously been observed for β-substituted enones. 4 According to literature precedence, 5 cisconfiguration of the formed product could be expected. -4a-Methyloctahydrophenanthrene Vol. 13, No. 5, 2002 The pivotal intermediate 9 6 was easily prepared in three steps from 1,3-cyclohexanedione (6) and 1-bromo-2-(2-iodoethyl)benzene (5) in 37% yield. The lat...

Synthesis Studies on the Lomaiviticin A Aglycone Core: Development of a Divergent, Two-Directional Strategy

“…Acylation of the sterically hindered alcohol with 2-iodobenzoyl chloride furnished the ester 57 , a substrate for Heck-type cyclization. Toward that end, treatment of this aryl iodide under modified Jeffrey conditions led to formation of a tricyclic product 58 that effectively established the required C(11a)/C(11b) connection for lomaiviticinone. This model system points out the possible, but there are other approaches that also may be fruitful; work toward that goal is ongoing. …”

2-(2-Bromophenyl)acetic acid

“…The title compound, (I), has many applications in various syntheses, for example, in the synthesis of heterocyclic compounds (Deshpande et al, 2008) and in the synthesis of AMPA antagonists -substituted quinoxalinediones, quinolones, isatinoximes and benzodiazepine derivatives (Pratt et al, 2000). It can also be used in a gas chromatography as a phase transfer catalyst (Rodriguesa et al, 2002). Herein we report its crystal structure.…”

“…For applications of the title compound, see: Deshpande et al (2008); Rodriguesa et al (2002); Pratt et al (2000). For related structures, see: Hodgson & Asplund (1991); Harris et al (1994); Hartung et al (2004); Yuan et al (2008); Jasinski et al(2010); Li et al (2010).…”