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

Abstract

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...

A carbonate-forming Baeyer-Villiger monooxygenase

“…Epoxide opening facilitated by abstraction of C18 α-proton leads to an a-alcohol intermediate, which can form the epoxy alkoxide 20 and readily rearrange across the 1,5 diketone system to afford 9 . This last step is analogous to the reported Lewis-acid-promoted conversion of an α-hydroxy β-dicarbonyl compound to a carbonate 21 , 22 . Alternatively, direct addition of Fl-4a-OO-at C21 of 11 may also take place ( Supplementary Fig.…”

Molecular Rearrangements: Part 2. Other Reactions

“…The presence of a Ag n 0 /Ag n + redox couple facilitates a non-classical electron-transfer process, involving chemical reactions interposed between two electron-transfer steps occurring in opposite directions. 34 The reaction was shown to proceed through a novel α-hydroxy β-dicarbonyl to α-ketol ester rearrangement mechanism, which is supported by the isolation of the carbonate (45) intermediate. 33 The decarboxymethylation of substituted α-hydroxy-α-carbomethoxy hexacyclic substituted ketones (43), one of these used as an advanced intermediate in the synthesis of the alkaloid aspidophytine, can be effected by heating with MgI 2 in CH 3 CN in good yields (75-84%) (Scheme 12).…”

“…Metal alkoxides, such as sodium benzylate, in catalytic amounts promote the [2,3]-Wittig rearrangement of silyl enolates (34), to afford the corresponding rearrangement product (35) in good yields at room temperature (Scheme 8). 23 It has been demonstrated that the oxygen anion of initially formed product (36) effectively catalysed the [2,3]-Wittig rearrangement as a Lewis base.…”

Furan Çekirdekli Bileşiklerin Mikrodalga Destekli Molekül İçi Diels Alder Halkalaşma Reaksiyonları

“…Bu reaksiyonlarda genellikle dien olarak furan türevi bileşikler kullanılır. [1] Bunun en önemli sebebi furanın tiyofen ve pirole göre daha düşük aromatikliğe sahip olmasıdır. Yine de daha zor reaksiyon veren pirol ve tiyofen türevli bileşikler de diels alder reaksiyonlarında çeşitli ön işlemlerden sonra kullanılabilmektedir [2].…”