Reaction of β-Diketones with Peracids

House, Herbert O.; Gannon, Walter F.

doi:10.1021/jo01100a030

Cited by 40 publications

(11 citation statements)

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“…The success of this reaction is probably due to activation of the ester by chelation of the Mg II cation with both C¼O groups. Analogous base-catalyzed rearrangements of ahydroxy b-diketones to a-keto esters have been reported by Davis et al [29] and others [30] [31].…”

Section: Methodssupporting

confidence: 58%

Total Synthesis of the Alkaloid (±)‐Aspidophytine Based on Carbonyl Ylide Cycloaddition Chemistry

Mejía-Oneto¹,

Padwa²

2008

Helvetica Chimica Acta

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The Rh II -catalyzed cycloaddition cascade of an indolyl-substituted a-diazo imide was used for the total synthesis of the complex pentacyclic alkaloid (AE)-aspidophytine. Treatment of the resulting dipolar cycloadduct with BF 3 · OEt 2 induces a domino fragmentation cascade. The reaction proceeds by an initial cleavage of the oxabicyclic ring and formation of a transient N-acyl iminium ion which reacts further with the adjacent tert-butyl ester and sets the required lactone ring present in aspidophytine. A three-step sequence was then used to remove both the ester and OH groups. Subsequent functional group manipulations allowed for the high-yielding conversion to (AE)-aspidophytine.

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Section: Methodssupporting

confidence: 58%

Total Synthesis of the Alkaloid (±)‐Aspidophytine Based on Carbonyl Ylide Cycloaddition Chemistry

Mejía-Oneto¹,

Padwa²

2008

Helvetica Chimica Acta

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“…Analogous base-catalyzed rearrangements of α-hydroxy β-diketones to α-keto esters have been reported by Davis et al 14 and others. [15][16][17][18] The pathway shown in Scheme 4 is supported by the isolation of carbonate 10 when the reaction of 7 was carried out with Cs 2 CO 3 in acetonitrile at 81 °C for 1 h. Under these conditions, carbonate 10 was obtained in 75% yield and could be readily hydrolyzed to 9 when subjected to mild acidic conditions.…”

mentioning

confidence: 91%

Lewis acid-promoted α-hydroxy β-dicarbonyl to α-ketol ester rearrangement

Hong

Mejía-Oneto

Padwa

2006

Tetrahedron Letters

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The decarbomethoxylation reaction of a substituted α-hydroxy-α-carbomethoxy pentacyclic substituted ketone, used as an advanced intermediate in the synthesis of the alkaloid aspidophytine, can be elected by heating with MgI 2 in CH 3 CN. The reaction was shown to proceed by a novel α-hydroxy β-dicarbonyl to α-ketol ester rearrangement. It was possible to isolate a carbonate intermediate in 75% yield, thereby providing support for the proposed pathway.The Rh(II)-catalyzed cyclization/cycloaddition cascade of α-diazo carbonyl compounds developed in our laboratories has proven to be an extremely efficient process for the synthesis of a variety of aza polycyclic ring systems. 1 Intramolecular trapping of the carbonyl ylide dipole generated from the domino Rh(II)-reaction proceeds in a highly regio and stereoselective manner and has been used in the construction of several heterocyclic natural products. 2-4 For example, this domino cascade was successfully applied in our laboratory toward the synthesis of the alkaloid (±)-lycopodine (Scheme 1). 5 The initially formed cycloadduct 2, obtained from the Rh(II)-cascade reaction of 1, was treated with a Lewis acid and provided the rearranged tetracyclic lactam 3 derived from a Pictet-Spengler type cyclization of a transient Nacyliminiumion. 6 Although lactam 3 contains the proper ring skeleton needed for lycopodine, it is overfunctionalized. The three-step sequence that we used to remove both the hydroxyl and ester functionalities involved (i) a Barton-McCombie deoxygenation, 7 (ii) ester hydrolysis, and (iii) thermal decarboxylation of the resulting carboxylic acid. Compound 4 was eventually transformed into (±)-lycopodine.More recently, in our successful synthesis of the alkaloid (±)-aspidophytine, 8 it was also necessary to remove the hydroxyl and carbomethoxy functionalities from the advanced intermediate 7, which was obtained by treating cycloadduct 6 with BF 3 ·OEt 2 (Scheme 2). In this case, the three-step protocol previously used for lycopodine resulted in only very low yields of ketone 8. During the course of preparing ketone 8 for an eventual synthesis of aspidophytine, we investigated the dealkoxycarbonylation-dehydroxylation of lactam 7 and related systems under several reaction conditions. The results that we obtained are not only useful for the future construction of molecules of the type discussed here, but also allow for the facile chemoselective removal of either (or both) the hydroxyl and/or carboalkoxy functionalities.Dealkoxycarbonylation of activated esters via nucleophilic dealkylation 9 represents a one-step process for the removal of the alkyl ester entity, particularly when structurally hindered. The reaction usually involves heating of the substrate in a dipolar aprotic solvent in the presence of a nucleophile. Following Krapcho's original development of this approach, 10 which employed NaCl in DMSO, many other nucleophiles have been found to be applicable, 9 including thiolates, tert-but-oxide, thiocyanate, amines, and acetate. For malona...

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“…This transformation, well‐known as the Rubottom reaction, [17] although being a widespread and useful α‐hydroxylation reaction in organic synthesis, [18] requires prederivatization of carbonyl compounds to silyl enol ethers and occasionally TBAF deprotection of the firstly formed silyl ether, which represent drawbacks from the step‐economic point of view. In this context, magnesium monoperphthalate (MMPP), [19] although being cheaper, stable and practical peroxy acid than popular MCPBA, was only briefly studied by Gannon and House in the direct oxidation of two α‐substituted β‐diketones [20] . The oxidation proved to be unselective, observing the formation of α‐hydroxy‐β‐diketones, together with the carboxylic acids and α‐hydroxy ketones.…”

Section: Methodsmentioning

confidence: 99%

Magnesium Monoperphthalate (MMPP): a Convenient Oxidant for the Direct Rubottom Oxidation of Malonates, β‐Keto Esters, and Amides

2021

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A mild and convenient protocol for the α‐hydroxylation of α‐substituted malonates, β‐ketoesters, and β‐ketoamides is disclosed. Cheap and stable magnesium monoperphthalate (MMPP) was effective for a first direct α‐hydroxylation protocol of the Rubottom oxidation, providing tartronic esters, cyclic α‐hydroxy β‐ketoesters and amides in good to high yields, when working at room temperature and in ethanol as the solvent. The protocol has been successfully scaled up to gram quantity.

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Reaction of β-Diketones with Peracids

Cited by 40 publications

References 0 publications

Total Synthesis of the Alkaloid (±)‐Aspidophytine Based on Carbonyl Ylide Cycloaddition Chemistry

Total Synthesis of the Alkaloid (±)‐Aspidophytine Based on Carbonyl Ylide Cycloaddition Chemistry

Lewis acid-promoted α-hydroxy β-dicarbonyl to α-ketol ester rearrangement

Magnesium Monoperphthalate (MMPP): a Convenient Oxidant for the Direct Rubottom Oxidation of Malonates, β‐Keto Esters, and Amides

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