Thermal and base-catalyzed rearrangements of diacyl carbinols

Rubin, M. B.; Inbar, Shai

doi:10.1016/s0040-4039(01)86778-2

Cited by 16 publications

(5 citation statements)

References 16 publications

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“…b. Diacylcarbinol Rearrangement (Scheme ) . This rearrangement is reaction 3 in the general scheme and has only been observed with compounds where the diacyl carbinol moiety is not entirely incorporated in a single ring. In the mechanism proposed, the initial oxyanion 102 attacks a neighboring carbonyl group with formation of an epoxide intermediate 104 which undergoes rebonding and eventual protonation to form esters.…”

Section: Rearrangement Reactionsmentioning

confidence: 93%

The Chemistry of Vicinal Polycarbonyl Compounds

2000

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Section: Rearrangement Reactionsmentioning

confidence: 93%

The Chemistry of Vicinal Polycarbonyl Compounds

2000

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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.…”

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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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“…To overcome the potential pitfall caused by the reversibility of the reaction, we thought about exploiting two strategies to render the process highly enantioselective: a) kinetic resolution of the rearranged product. The α‐hydroxy‐β‐dicarbonyls are known to undergo further isomerization to afford the corresponding α‐ketol esters . If the minor enantiomer underwent the acyl migration faster than its antipode ( k 1 > k 2 , k 4 > k 3 ), then an ee enhancement of 2 would be expected .…”

Section: Methodsmentioning

confidence: 99%

“…The a-hydroxy-b-dicarbonyls are known to undergo further isomerization to afford the corresponding a-ketol esters. [12] If the minor enantiomer underwent the acyl migration faster than its antipode (k 1 > k 2 , k 4 > k 3 ), then an ee enhancement of 2 would be expected. [13][14][15] Since the rearrangement of 2 to 3 is,d epending on the reaction conditions,a lso reversible, [16] reaction conditions would have to be carefully fine-tuned to favor the forward reactions;b)asubsequent kinetically competent hemiacetalization reaction converting 5 into the more complex product 6.Inthis case,the major enantiomer should react faster than the minor one to amplify the product ee value (k 1 > k 2 , k 3 > k 4 ).…”

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Catalytic Enantioselective α‐Ketol Rearrangement

Andres

Wang

2018

Angew Chem Int Ed

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Ahighly enantioselective a-ketol rearrangement has been developed. In the presence of ac hiral Cu-bisoxazoline complex, achiral b-hydroxy-a-dicarbonyls were isomerized to chiral a-hydroxy-b-dicarbonyls and their bicyclic derivatives in excellent yields and enantioselectivities.E nantioenriched 2-acyl-2-hydroxy cyclohexan-1-ones,d ihydroxyhexahydrobenzofuranones,a nd dihydroxyhexahydro-cycloheptafuranones,w ith up to three stereocenters,w ere readily prepared from achiral starting materials in one operation. The reaction is applicable to the desymmetrization of meso substrates and kinetic resolution of racemic alcohols. Scheme 1. The a-ketol rearrangement.

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Thermal and base-catalyzed rearrangements of diacyl carbinols

Cited by 16 publications

References 16 publications

The Chemistry of Vicinal Polycarbonyl Compounds

The Chemistry of Vicinal Polycarbonyl Compounds

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

Catalytic Enantioselective α‐Ketol Rearrangement

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