Constructing Quaternary Stereogenic Centers Using Tertiary Organocuprates and Tertiary Radicals. Total Synthesis of trans-Clerodane Natural Products

Abstract

A new concise construction of trans-clerodane diterpenoids is reported in which oxacyclic and trans-hydronaphthalene fragments are coupled, and the critical C9-quaternary carbon stereocenter formed stereoselectively, by 1,6-addition of a tertiary cuprate or a tertiary carbon radical to β-vinylbutenolide. This strategy is specifically illustrated by total syntheses of (-)-solidagolactone (4), (-)-16-hydroxycleroda-3,13-dien-15,16-olide (5, PL3), and (-)-annonene (6).

Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling

“…This severe steric interaction had previously prevented the preparation of the N -phthalimidoyl oxalate derivative. 17 However, acylation of 69 with methyl chlorooxoacetate proceeded in excellent yield. In situ hydrolysis with aqueous CsOH allowed pure cesium oxalate 44 tobe isolated in one step and high yield from alcohol 69 without the use of chromatography.…”

“…Coupling of oxalate 44 (1.5 equiv) with commercially available 4-vinylfura N -2-one (1.0 equiv) proceeded with perfect diastereo- and regioselectivity in 98% yield to give trans -clerodane 70 , a natural product that is a versatile precursor of many other members of the trans-clerodane family. 17 …”

Constructing Quaternary Carbons from N-(Acyloxy)phthalimide Precursors of Tertiary Radicals Using Visible-Light Photocatalysis

“…To prepare more sterically demanding substrates, coupling of acid chlorides with the potassium salt of N -hydroxyphthalimide in the presence of a crown ether is most effective (Figure 1B). 4 As summarized in Figure 1, ( N -acyloxy)phthalimides of variable structural complexity were prepared in high yield by these methods. These radical precursors are typically crystalline solids, which are stable to benchtop storage, ambient light, biphasic aqueous purification conditions, and chromatography on silica gel.…”

“…1,2 The utility of this general method for combining complex carbon fragments has recently been highlighted in several total synthesis investigations in our laboratories. 3,4 …”

Neue Entwicklungen auf dem Gebiet der Minisci‐Reaktion

“…[52] In einer Minisci-Reaktion macht dieser Ansatz aufgrund des formal oxidativen Charakters der Umsetzung allerdings den Einsatz eines externen Oxidationsmittels nçtig. [55][56][57] Der Einsatz von N-Acyloxyphthalimiden in Minisci-Reaktionen wurde 2017 erstmals in zwei Arbeiten von Shang, Fu und Mitarbeitern beschrieben (Schema 13). Diese Verbindungen wurden von Okada, Okamoto und Oda ursprünglich zur Erzeugung von Alkylradikalen entwickelt, und sind in den letzten Jahren beliebte Werkzeuge der organischen Synthesechemie geworden, unter anderem aufgrund vieler interessanter Anwedungen der Gruppe um Baran, [54] und früherer einflussreicher Studien von Overman.…”