A concise total synthesis of (±)-cipadonoid B from synthetic azedaralide

Faber, Jonathan M.; Williams, Craig M.

doi:10.1039/c0cc04698a

Cited by 22 publications

(15 citation statements)

References 39 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 The final solution, forming this bond by an intramolecular reaction (in this case a sigmatropic rearrangement), is the standard method to surmount this challenge. 6 Much less common is the use of a bimolecular reaction to join two complex fragments and form two new stereocenters, at least one of which is quaternary. 7,8 Reactions between nucleophilic carbon radicals and electrondeficient alkenes have several attractive features for use in coupling of complex fragments, and in particular, tertiary carbon radicals are especially well-suited for forming quaternary stereocenters by uniting complex fragments through sp 3 −sp 3 σ bonds.…”

Section: Introductionmentioning

confidence: 99%

Fragment Coupling with Tertiary Radicals Generated by Visible-Light Photocatalysis

2016

View full text Add to dashboard Cite

Convergent synthesis strategies in which a target molecule is prepared by a branched approach wherein two or more complex fragments are combined at a late stage are almost always preferred over a linear approach in which the overall yield of the target molecule is eroded by the efficiency of each successive step in the sequence. As a result, bimolecular reactions that are able to combine complex fragments in good yield and, where important, with high stereocontrol are essential for implementing convergent synthetic strategies. Although intramolecular reactions of carbon radicals have long been exploited to assemble polycyclic ring systems, bimolecular coupling reactions of structurally complex carbon radicals have rarely been employed to combine elaborate fragments in the synthesis of structurally intricate molecules. We highlight in this Account recent discoveries from our laboratories that demonstrate that bimolecular reactions of structurally elaborate tertiary carbon radicals and electron-deficient alkenes can unite complex fragments in high yield using nearly equimolar amounts of the two coupling partners. Our discussion begins by considering several aspects of the bimolecular addition of tertiary carbon radicals to electron-deficient alkenes that commend these transformations for the union of structurally complex, sterically bulky fragments. We then discuss how in the context of synthesizing rearranged spongian diterpenoids we became aware of the exceptional utility of coupling reactions of alkenes and tertiary carbon radicals to unite structurally complex synthetic intermediates. Our initial investigations exploit the early report of Okada that N-(acyloxy)phthalimides reductively fragment at room temperature in the presence of visible light and catalytic amounts of the photocatalyst Ru(bpy)3Cl2 to form carbon radicals that react with alkenes. We show that this reaction of a tertiary radical precursor and an enone can combine two elaborate enantioenriched fragments in good yield with the formation of new quaternary and secondary stereocenters. As a result of the ready availability of tertiary alcohols, we describe two methods that were developed, one in collaboration with the MacMillan group, to generate tertiary radicals from tertiary alcohols. In the method that will be preferred in most instances, the tertiary alcohol is esterified in high yield to give a tert-alkyl hemioxalate salt, which-without purification-reacts with electron-deficient alkenes in the presence of visible light and an Ir(III) photocatalyst to give coupled products having a newly formed quaternary carbon in high yield. Hemioxalate salts containing Li, Na, K, and Cs countercations can be employed in this reaction, whose only other product is CO2. These reactions are carried out using nearly equimolar amounts of the addends, making them ideal for coupling of complex fragments at the late stage in a synthetic sequence. The attractive attributes of the fragment-coupling chemistry that we discuss in this Account are illustrated by an enanti...

show abstract

Section: Introductionmentioning

confidence: 99%

Fragment Coupling with Tertiary Radicals Generated by Visible-Light Photocatalysis

2016

View full text Add to dashboard Cite

show abstract

“…Based upon cipadonoid B 359, 118 Faber et al further reported a concise and enantioselective total synthesis of proceranolide 364, khayasin 365 and mexicanolide 366 (Scheme 2). First, compound 364 was obtained from 370 by epoxidation and cyclization; then, compound 365 was afforded by acylation of 364; nally, conversion of 364 to 366 in the presence of Jones reagent was achieved.…”

Section: Khayasin Proceranolide and Mexicanolidementioning

confidence: 99%

Recent progress in the chemistry and biology of limonoids

Zhang

2017

RSC Adv.

View full text Add to dashboard Cite

show abstract

“…The intact limonoid framework is characterized by a 4,4,8‐trimethyl‐17‐furyl‐13α‐androstane, but this family encompasses a diverse array of structural architectures as a result of oxidations and skeletal rearrangements. Not surprisingly, the unique architectures and the wide spectrum of biological properties of limonoids have attracted keen interest from the synthesis community,4 and for example, azadiradione,5 cipadonoid,6a mexicanolides,6b and azadirachtin have been synthesized 7. Herein, we describe the first total synthesis of (±)‐limonin ( 1 ).…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis of Limonin

et al. 2015

View full text Add to dashboard Cite

Limonoids are highly oxygenated C13α-triterpenes and common secondary metabolites. Several hundred congeners have been isolated to date. The first total synthesis of (±)-limonin, the flagship congener of the limonoids, is now reported and features 1) a tandem radical cyclization generating the BCD ring system with the C13α configuration that is essential to the limonoids and a Robinson annulation to construct the limonoid androstane framework, 2) a singlet-oxygen cycloaddition and a Baeyer-Villiger oxidation to synthesize the highly oxidized D ring, and 3) a Suárez reaction to construct the unique AA' ring system.

show abstract

A concise total synthesis of (±)-cipadonoid B from synthetic azedaralide

Abstract: The tetranortriterpene cipadonoid B was efficiently constructed from synthetic azedaralide in a one-pot cascade, via the underutilised ketal-Claisen rearrangement.

Cited by 22 publications

References 39 publications

Fragment Coupling with Tertiary Radicals Generated by Visible-Light Photocatalysis

Fragment Coupling with Tertiary Radicals Generated by Visible-Light Photocatalysis

Recent progress in the chemistry and biology of limonoids

Total Synthesis of Limonin

Contact Info

Product

Resources

About