Enantioselective cyclization of enamide-ynes and application to the synthesis of the kopsifoline core

Corkey, Britton K.; Heller, Stephen T.; Wang, Yiming; Toste, F. Dean

doi:10.1016/j.tet.2013.02.091

Cited by 26 publications

(17 citation statements)

References 47 publications

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“…34 Although we 13a and others 11 had previously reported BINOL-derived mononuclear phosphoramiditegold(I) complexes, reactions catalyzed by these complexes had not exhibited significant enantioselectivity. Due to the 2-coordinate linear geometry of gold, we anticipated substantial difficulty in achieving good enantioselectivity with these mononuclear complexes.…”

Section: Development Of Chiral Phophoramidite and Phosphite Ligands Fmentioning

confidence: 72%

Development of Catalysts and Ligands for Enantioselective Gold Catalysis

2013

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CONSPECTUS The use of Au(I) complexes for the catalytic activation of C-C π-bonds has been the subject of intense investigation in the last decade or so. The facile formation of carbon-carbon and carbon-heteroatom bonds facilitated by gold naturally led to efforts to render these transformations enantioselective. Early examples of enantioselective gold-catalyzed transformations have focused on bis(phosphinegold) complexes derived from axially chiral scaffolds. Although these complexes were highly successful in some reactions like cyclopropanation, careful choice of the weakly coordinating ligand (or counterion) was needed to obtain high levels of enantioselectivity for the case of allene hydroamination. These counterion effects led us to use the anion itself as a source of chirality, which was successful in the case of allene hydroalkoxylation. In order to expand the scope of reactions amenable to enantioselective gold catalysis to cycloadditions and other carbocyclization processes, a new class of mononuclear phosphite and phosphoramidite ligands was developed to supplement the previously widely utilized phosphines. Finally carbene ligands, in particular, the acyclic diaminocarbenes, have also been successfully applied to enantioselective transformations.

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Section: Development Of Chiral Phophoramidite and Phosphite Ligands Fmentioning

confidence: 72%

Development of Catalysts and Ligands for Enantioselective Gold Catalysis

2013

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“…10 By mimicking what is the likely biosynthesis of the kopsifolines, 1 a late-stage C21–C3 bond formation via a transannular enamide alkylation of an alcohol-derived C21 iodide within the Aspidosperma alkaloid skeleton was developed and implemented to complete the assemblage of the kopsifoline skeleton (eq 1) in a route that directly provides the natural product in its final indolenine oxidation state. The studies further established the kopsifoline absolute configuration as enantiomeric to the Aspidosperma alkaloids including fendleridine, but analogous to that found within kopsinine.…”

Section: Introductionmentioning

confidence: 99%

Total Syntheses of (−)-Kopsifoline D and (−)-Deoxoapodine: Divergent Total Synthesis via Late-Stage Key Strategic Bond Formation

Lee

Boger

2014

J. Am. Chem. Soc.

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Divergent total syntheses of (−)-kopsifoline D and (−)-deoxoapodine are detailed from a common pentacyclic intermediate 15, enlisting the late-stage formation of two different key strategic bonds (C21–C3 and C21–O–C6) unique to their hexacyclic ring systems that are complementary to its prior use in the total syntheses of kopsinine (C21–C2 bond formation) and (+)-fendleridine (C21–O–C19 bond formation). The combined efforts represent the total syntheses of members of four classes of natural products from a common intermediate functionalized for late-stage formation of four different key strategic bonds uniquely embedded in each natural product core structure. Key to the first reported total synthesis of a kopsifoline that is detailed herein was the development of a transannular enamide alkylation for late-stage formation of the C21–C3 bond with direct introduction of the reactive indolenine C2 oxidation state from a penultimate C21 functionalized Aspidosperma-like pentacyclic intermediate. Central to the assemblage of the underlying Apidosperma skeleton is a powerful intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole that provided the functionalized pentacyclic ring system 15 in a single step in which the C3 methyl ester found in the natural products served as a key 1,3,4-oxadiazole substituent, activating it for participation in the initiating Diels–Alder reaction and stabilizing the intermediate 1,3-dipole.

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“…As in the Van der Eycken study, the spirocycle 205 was a side‐product in this reaction, with the major fused indole products 206 presumably being formed via a 1,2‐migration of spirocycle 205 . Next, Toste and co‐workers reported a single example of a Pd II catalysed spirocyclisation in their studies towards the synthesis of the kopsifoline . Submission of alkyne 207 to the asymmetric Pd II conditions furnished the spirocycle 208 in moderate yield and good enantioselectivity.…”

Section: Indole Dearomatisationsmentioning

confidence: 99%

“…[115] As in the Vander Eyckens tudy, the spirocycle 205 was as ide-product in this reaction, with the major fused indole products 206 presumably being formed via a1 ,2-migration of spirocycle 205.N ext, To ste and co-workers reported as ingle example of aP d II catalysed spirocyclisation in their studies towards the synthesis of the kopsifoline. [116] Submission of alkyne 207 to the asymmetricP d II conditions furnished the spirocycle 208 in moderate yield and good enantioselectivity.I nterestingly,t he authors noted an improved reaction profileu nder acidic conditions. Next, Enders and co-workers reported an intermolecular variant,c ombining both conjugate addition and alkyne activation with 209 and 210 to form as ingle example of spirocyclic indolenine 212 as am echanistic probe.…”

Section: Additiont Oalkenesalkynesand Allenesmentioning

confidence: 99%

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Synthesis of Spirocyclic Indolenines

James

O’Brien

Taylor

et al. 2015

Chemistry A European J

299

119

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This Review provides an in-depth account of the synthesis of spirocyclic indolenines. Over the last 77 years, a wide array of diverse synthetic methods has been developed in order to generate these synthetically useful and biologically important spirocyclic scaffolds. The main synthetic strategies discussed are grouped into three main categories, namely interrupted Fischer indolisations, dearomatisation reactions of indoles and condensation reactions. The historical background, common synthetic challenges, current state-of-the-art and future perspectives of this field are examined.

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Enantioselective cyclization of enamide-ynes and application to the synthesis of the kopsifoline core

Abstract: We report the palladium-catalyzed enantioselective cyclization of 1,6-enamidynes to form spirocyclic ring systems. We applied this methodology to the concise synthesis of the skeletal core of the kopsifoline alkaloids.

Cited by 26 publications

References 47 publications

Development of Catalysts and Ligands for Enantioselective Gold Catalysis

Development of Catalysts and Ligands for Enantioselective Gold Catalysis

Total Syntheses of (−)-Kopsifoline D and (−)-Deoxoapodine: Divergent Total Synthesis via Late-Stage Key Strategic Bond Formation

Synthesis of Spirocyclic Indolenines

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