Formal Total Synthesis of (±)-Estrone via the Furano Diene Approach

Abstract

We present in this report the development and realization of a novel formal total synthesis of estrone (1) via the Torgov diene (24) by the furano diene approach, first attempted by Woodward in 1937. The core ring structure 16 was established by an acid-mediated regioselective and stereospecific cyclization of the endo-oxabicyclo[2.2.1]heptene derivative 14, which is readily available from the AlCl(3)-catalyzed Diels-Alder cycloaddition of 2-(3-methoxyphenethyl)furan (4) and dimethyl maleate. The mechanistic pathway of this S(N)' type cyclization is discussed, and the earlier perspectives in our preliminary report (Org. Lett. 2004, 6, 1333) are corrected.

Unusual Structure-Energy Correlations in Intramolecular Diels–Alder Reaction Transition States

“…The Diels–Alder reaction of furan has been widely used in the synthesis of complex targets and as a probe for the investigation of substituent effects [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. We recently reported a comprehensive, computational and experimental study of halogenation effects in intramolecular Diels–Alder reactions [19].…”

Applications of Friedel–Crafts reactions in total synthesis of natural products

“… 143,144 Another common synthetic pathway is the equivalent acid-mediated FC alkylation reaction of olefins. 145 The natural diptoindonesin D 130 and pauciflorial F 131 have been extracted from the acetone extract of the tree bark of Hopea dryobalanoides 146 and the stem barks of Vatica pauciflora 147 respectively. Yang and co-workers established an efficient method for the construction of several dibenzo[ a , d ] cycloheptenes through FC alkylation reaction.…”

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

“…Separation of the desired isomer by crystallization and cleavage of the methyl ether finally gave estrone ( 12 ). Three of the four stereocenters of estrone [155–163] were set in a single conjugate addition and enolate alkylation reaction with excellent stereocontrol [44]. …”