Gibbane synthons via hexahydrofluorenones. Intramolecular Reformatsky reaction

Abstract

An efficient synthesis of hexahydrofluorene-2,9-dione and 7-methoxyhexahydrofluorene-2,9-dione from the appropriate phenylpyruvic acids is described. Their conversion to -bromo esters and amides as well as the intramolecular Reformatsky reaction of these substances to provide gibbane synthons is detailed.Synthetic efforts directed toward the gibberellins [gibberellic acid (1)] have led to known gibberellins,3 degradation products thereof,4 and gibbane synthons.5 Our interest in this problem lay in devising an efficient synthetic route to hexahydrofluorenones 7a and 7b, which could in turn lead to tetracyclic gibbane synthons.Although frans-2-phenyl-o-oxo-l-cyclohexanecarboxylic acid (4) had previously been cyclized to dione 7a, no yields were specified and, moreover, the acid was obtained as the minor product from the Diels-Alder reaction of 2-ethoxybutadiene and irans-cinnamic acid.6 It seemed reasonable that the corresponding cis acid 5a would be more amenable to cyclization than its trans counterpart. In addition, the fact that the dissolving metal reduction of 3,4-diphenylcyclohex-2-en-l-one (3a) affords m-3,4-diphenylcyclohexanone7 augured well for a method of preparing the requisite cis acid, since the carboxylate anion of acid 3b should play a similar role to that of the 3-phenyl substituent in ketone 3a.To this end, the condensation between p-methoxyphenylpyruvic acid and methyl vinyl ketone was achieved in aqueous methanolic sodium hydroxide, yielding 1-hydroxy-2-(p-methoxyphenyl)-5-oxo-l-cyclohexanecarboxylic acid (2c) as a single diastereomer in high yield. Several analogous annelations have been reported between phenylpyruvic acid and benzalacetone,8•9 p-methoxybenzylidene acetone,9 and ethyl(1) Taken in part from the Ph.D. thesis of , E. C.,

Synthesis of Functionalized Bicyclo[3.2.1]octanes and Their Multiple Uses in Organic Chemistry

“…A related strategy based on the cyclization of vinyl halides to a carbonyl function was reported shortly after. While the Grignard reagent derived from 128 75 failed to give any bridged compound, the corresponding cuprate gave the tricyclic methylene ketone 129 in 60% yield. 76 This methodology was also employed for a more direct access to ketone 127 77 and used in a total synthesis of gibberellic acid.…”

The Taiwaniaquinoids: A Review

“…Cheng postulated that the abeo-abietanes found in T. cryptomerioides arise from a pinacol-type rearrangement of 6,7-dihydroxyferruginol (19), possibly derived from 6,7-dehydroferruginol (20), which is also found in the leaves of T. cryptomerioides (Scheme 1). 2a This kind of rearrangement gives rise to the 5(6f7)abeo- † Taken in part from the Ph.D. dissertation of Joel M. Shimkus, University of Georgia, Athens, GA (2009).…”

“…18 Ziegler and Condon used the PPA cyclization of phenylcyclohexanecarboxylic acid derivatives to construct their gibbane synthons (35 f 36, eq 4). 19 Ramana extended the methodology of Dev, Rand, and Conia by reacting ethyl cyclohexene-1-carboxylate (37) with variously substituted methoxylated arenes under acidic conditions (eq 5). 20 Interestingly, Ramana found that the use of H 2 SO 4 caused Michael addition to occur first, followed by intramolecular Friedel-Crafts acylation, whereas the use of PPA caused 1,2addition to the ester to take place, followed by a Nazorov cyclization.…”

“…34 , eq 3) . Ziegler and Condon used the PPA cyclization of phenylcyclohexanecarboxylic acid derivatives to construct their gibbane synthons ( 35 → 36 , eq 4) . Ramana extended the methodology of Dev, Rand, and Conia by reacting ethyl cyclohexene-1-carboxylate ( 37 ) with variously substituted methoxylated arenes under acidic conditions (eq 5) .…”

Palladium(II)-katalysierte Domino-Reaktionen zur enantioselektiven Synthese von Confluentin, Daurichromen- und Rhododaurichromansäure Untersuchungen zur Synthese von Aglaroxin A

“…55%) erhalten werden. [97] Die Kupplung des lithiierten Esters Es sind zwei Methoden zur Darstellung in der Literatur beschrieben. Bei der ersteren handelt es sich um eine oxidative Diolspaltung des Weinsäuremethylesters (134), der mit Periodsäure zum Glyoxylester 135 reagiert.…”