Palladium(II)-catalyzed 1,3-dipolar cycloaddition of nitrones with enol ethers

Hori, Koichi; Ito, Junji; Ohta, Tetsuo; Furukawa, Isao

doi:10.1016/s0040-4020(98)00776-5

“…The uncatalyzed intramolecular dipolar cycloadditions to form Setigerumine I ( 1 ) and Isosetigerumine I ( 11 ) had reasonably low energy barriers in solution Δ G TS,Dipolar =19.3 kcal mol −1 ; Δ H TS,Dipolar =18.6 kcal mol −1 , and Δ G TS,Dipolar =17.2 kcal mol −1 ; Δ H TS,Cope =16.6 kcal mol −1 , respectively (Figure 2). While these energies agree with our experimental observations, the possible activation of nitrones 10 and 10′ by Lewis‐acidic oxidants cannot be ruled out at this stage [17, 18] …”

Section: Methodssupporting

confidence: 85%

Synthesis of (±)‐Setigerumine I: Biosynthetic Origins of the Elusive Racemic Papaveraceae Isoxazolidine Alkaloids**

Serna

¹

,

Kürti

²

,

Siitonen

³

2021

Angewandte Chemie

1

0

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The biosynthetic origins of the structurally related racemic isoxazolidine Papaveraceae alkaloids Setigerumine I, Dactylicapnosinine and Dactylicapnosine have remained elusive since their original isolation over two decades ago. Herein we report the first biosynthetic hypothesis for their formation and, inspired by it, the first synthesis of (±)‐Setigerumine I with accompanying computational rationale. Based on the results, these isoxazolidine alkaloids arise from racemizing oxidative rearrangements of prominent isoquinoline alkaloids Noscapine and Hydrastine. The key steps featured in this synthesis are a room temperature Cope elimination and a domino oxidation/inverse‐electron demand 1,3‐dipolar cycloaddition of an axially chiral, yet configurationally unstable, intermediate. The work opens this previously inaccessible family of natural products for biological studies.

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“…The uncatalyzed intramolecular dipolar cycloadditions to form Setigerumine I (1) and Isosetigerumine I (11) proceeded with reasonably low energy barriers in solution ΔGTS, Dipolar = 19.3 kcal/mol; ΔHTS,Dipolar = 18.6 kcal/mol, and ΔGTS, Dipolar = 17.2 kcal/mol; ΔHTS,Cope = 16.6 kcal/mol respectively (Figure2). While these energies agree with our experimental observations, the possible activation of nitrones 10 and 10' by Lewis-acidic oxidants cannot be ruled out at this stage 41.…”

supporting

confidence: 84%

“…While these energies agree with our experimental observations, the possible activation of nitrones 10 and 10' by Lewis-acidic oxidants cannot be ruled out at this stage. 41 We expected the intramolecular [3+2] reaction, taking nitrone 10 to Setigerumine I (1), to be an inverse electron-demand 1,3-dipolar cycloaddition reaction, as the nitrone dipole of 10 reacts with a reasonably electron-rich enol ether dipolarophile. These inverse electron-demand processes are markedly underdeveloped when compared to their normal electron-demand counterpairs.…”

mentioning

confidence: 99%

Synthesis of (±)‐Setigerumine I: Biosynthetic Origins of the Elusive Racemic Papaveraceae Isoxazolidine Alkaloids**

Serna

¹

,

Kürti

²

,

Siitonen

³

2021

View full text Add to dashboard Cite

The biosynthetic origins of the structurally related racemic isoxazolidine Papaveraceae alkaloids Setigerumine I, Dactylicapnosinine and Dactylicapnosine have remained elusive since their original isolation over two decades ago. Herein we report the first biosynthetic hypothesis for their formation and, inspired by it, the first synthesis of (±)‐Setigerumine I with accompanying computational rationale. Based on the results, these isoxazolidine alkaloids arise from racemizing oxidative rearrangements of prominent isoquinoline alkaloids Noscapine and Hydrastine. The key steps featured in this synthesis are a room temperature Cope elimination and a domino oxidation/inverse‐electron demand 1,3‐dipolar cycloaddition of an axially chiral, yet configurationally unstable, intermediate. The work opens this previously inaccessible family of natural products for biological studies.

show abstract

“…In the structure shown in Scheme 6.37 the two phosphorus atoms of the Tol-BINAP ligand and the two car- Furukawa et al also applied the above described palladium catalyst to the inverse electron-demand 1,3-dipolar cycloaddition of nitrones with vinyl ethers. However, all products obtained in this manner were racemic [81]. …”

Section: Palladium Catalysts For Reactions Of Nitronesmentioning

confidence: 97%