Enantioselective Synthesis of (+)-Estrone Exploiting a Hydrogen Bond-Promoted Diels−Alder Reaction

Abstract

Starting from Dane’s diene and methylcyclopentenedione, (+)-estrone is synthesized along the Quinkert−Dane route in 24% total yield. The key step is an enantioselective Diels−Alder reaction promoted by an amidinium catalyst as efficiently as by a traditional Ti-TADDOLate Lewis acid.

Progress towards synthetic chlorins with graded polarity, conjugatable substituents, and wavelength tunability

“…The product in each case ( C11 or C12 ) was suggested by a molecular ion peak upon ESI-MS analysis, but the trace quantity thwarted isolation. Alternatively, attachment of 1,3-dimethoxy-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene [59,60] (derived here from 2,6-dimethoxyphenyl boronic acid and pinacol) to the 15-position of the chlorin was investigated but found non-advantageous versus incorporation of the 2,6-dimethoxyaryl unit via the dipyrromethane in the Eastern half synthesis. The failure to incorporate the snap-on motif prompted return to an established route wherein the facially encumbering diphosphonate group is installed via the use of the Eastern half.…”

Transition‐Metal‐Mediated or ‐Catalyzed Syntheses of Steroids and Steroid‐Like Compounds

“…Last but not least, mention should also be made of syntheses of steroids accomplished by use of classical organic methodology. Typical examples include the syntheses of (+)-or (Ϯ)-estrone reported by Corey et al, [6][7][8] Pattenden et al, [9] Mukai et al, [10] Göbel et al, [11] and Li et al, [12] or the syntheses of ent-desmosterol, [13] ent-cholesterol, [14,15] and ent-estradiol [16] by Covey et al and by Rychnowski et al…”

Organocatalytic Asymmetric Formation of Steroids

“…[8] Later Quinkert et al showed that the Diels-Alder reaction could be promoted by the application of a Lewis acid catalyst. [10][11][12][13] Organocatalysis has opened a new dimension in asymmetric catalysis in the last decade. [10][11][12][13] Organocatalysis has opened a new dimension in asymmetric catalysis in the last decade.…”

“…EWG = electronwithdrawing group. [8][9][10][11][12][13] Our novel approach is based on the condensation of an aminocatalyst with an enal or 2,4-dienal to form either a dienamine or trienamine, respectively, which consist of a diene moiety attached to an activating and stereoinducing molecular handle. [20] A more recent development is the application of organocatalysis in targetoriented synthesis.…”