Catalytic Asymmetric Torgov Cyclization: A Concise Total Synthesis of (+)‐Estrone

Abstract

An asymmetric Torgov cyclization, catalyzed by a novel, highly Brønsted acidic dinitro-substituted disulfonimide, is described. The reaction delivers the Torgov diene and various analogues with excellent yields and enantioselectivity. This method was applied in a very short synthesis of (+)-estrone.

Disulfonimid‐katalysierte asymmetrische Reduktion von N‐Alkyliminen

“…Erst kürzlich präsentierten wir chirale Disulfonimide (DSI) als effektive Präkatalysatoren für die siliciumbasierte LewisSäure-Katalyse [11] und als starke Brønsted-Säure-Katalysatoren. [12] Unsere chiralen DSIs (2e-i)katalysieren die Reaktion tatsächlich besser als alternative Phosphorsäurekatalysatoren und stellten das Amin 4 mit einer hçheren Enantioselektivität dar . Nach einer sorgfältigen Untersuchung entwickelten wir Reaktionsbedingungen, mit denen die Reduktion von Imin 1a mit 5Mol-% des Katalysators (R)-DSI-2i, Hantzsch-Ester 3d (1.4 ¾quiv.)…”

Explosive Decomposition of a Melamine–Cyanuric Acid Supramolecular Assembly for Fabricating Defect‐Rich Nitrogen‐Doped Carbon Nanotubes with Significantly Promoted Catalysis

“…Benjamin List and co‐workers44 have very recently disclosed an organocatalytic procedure for obtaining Torgov's diene ( 97 ) and analogues with the aid of the enantiopure Bronsted acid catalyst dinitro‐substituted disulfonamide 120 . The methodology has been successfully applied to the short and concise total synthesis of (+)‐estrone (Scheme ).…”

Recent Progress in Steroid Synthesis Triggered by the Emergence of New Catalytic Methods

“…While many modern studies are focused on improving the synthesis and formation of functionalized Hajosh‐Parrish and Wieland‐Miescher ketones, the developments in organocatalysis allow to achieve rapid formation of significantly more complex intermediates. This subsection of the minireview highlights some of such studies that emerged from the groups of Hayashi, Hong and List …”

“…Thus, in 2014, Benjamin List's group reported an asymmetric synthesis of (+)‐estrone that was enabled by the chiral Brønsted acid catalysis (cf. Scheme ) . This synthesis was based on the racemic approach by Torgov, who in 1963, described an acid‐catalyzed cyclization of easily available diketone 184 into a steroidal Δ 8,14 ‐dienone 186 , which is a useful precursor to various steroids including estrone .…”