Organic synthesis based on the Beckmann fragmentation: generation of an electrophilic salt intermediate and successive C–C bond formation using Gilman reagents

Fujioka, Hiromichi; Matsumoto, Nao; Ohta, Reiya; Yamakawa, Maki; Shimizu, Nozomi; Kimura, Takashi; Murai, Kenichi

doi:10.1016/j.tetlet.2015.03.089

Cited by 7 publications

(3 citation statements)

References 17 publications

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“…To the best of our knowledge, this is the only method that allows the deprotection of acetals in the presence of ketals. In 2006, we reported the detailed study of the above chemistry including mechanistic considerations via a pyridinium-type salt intermediate B , which is an acidic species that reacts with many nucleophiles including H 2 O …”

Section: Introductionmentioning

confidence: 99%

Highly Discriminative and Chemoselective Deprotection/Transformations of Acetals with the Combination of Trialkylsilyl Triflate/2,4,6-Collidine

et al. 2018

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Acetals are the most useful protecting groups for carbonyl functional groups. In addition to the role of protection, they can also be used as synthons of carbonyl functions. Previously, we developed a chemoselective deprotection and nucleophilic substitution of acetals from aldehydes in the presence of ketals. This article describes the highly discriminative and chemoselective transformations of acetals bearing different substitution patterns, different types of acetals, as well as mixed acetals. These reactions can achieve the transformations that cannot be attained by conventional methods, and their results strongly suggest the combination of RSiOTf/2,4,6-collidine to promote such unprecedented phenomena.

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Section: Introductionmentioning

confidence: 99%

Highly Discriminative and Chemoselective Deprotection/Transformations of Acetals with the Combination of Trialkylsilyl Triflate/2,4,6-Collidine

et al. 2018

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“…Neighboring-group participation is a widely used approach to control stereochemistry in substitution reactions of carbohydrate compounds. − Most commonly, acyloxy groups, namely, the acetate, benzoate, and pivaloate esters, ,, are used to favor the 1,2- trans products with high selectivity. ,, Neighboring-group participation has not emerged as a useful approach for controlling stereochemistry in reactions involving acyclic acetals, however. − The use of neighboring-group participation to control stereochemistry in acyclic systems, as illustrated in eq , would be significant because it would provide access to the products expected from nucleophilic additions to α-alkoxy aldehydes that would be governed by the Felkin–Anh or related − stereochemical models. Such transformations, however, often give products with modest diastereoselectivity. ,,− …”

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Using Neighboring-Group Participation for Acyclic Stereocontrol in Diastereoselective Substitution Reactions of Acetals

Ramdular

Woerpel

2020

Org. Lett.

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Neighboring-group participation of an ester enabled stereocontrol in substitution reactions of acyclic acetals. The ester group formed a trans-fused dioxolenium ion intermediate, which underwent a substitution reaction at the acetal carbon atom to afford the product with high diastereoselectivity. Neighboring-group participation was confirmed by isolating dioxolane products resulting from nucleophilic addition at C-2 of a 1,3-dioxolenium ion intermediate. Using a pivaloate ester as the participating group in combination with strong nucleophiles produced substitution products with diastereoselectivities of ≥90:10.

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“…2). 16) Gilman reagents were found to be the best type of organometallic carbon nucleophile for this reaction, with several other more popular organometallic reagents, including organolithium and Grignard reagents, failing to provide good results. However, we previously found that the phosphonium salts derived from O,O-acetals and (o-tol) 3 P reacted smoothly with Grignard reagents.…”

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confidence: 99%

Beckmann Fragmentation and Successive Carbon–Carbon Bond Formation Using Grignard Reagents <i>via</i> Phosphonium Salt Intermediates

Fujioka

Matsumoto

Kuboki

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The intermediates formed during the Beckmann fragmentation of α-alkoxy and α-alkoxy-α-alkyl oxime acetates have been successfully trapped as phosphonium salts, which were subsequently reacted with a variety of Grignard reagents to give the corresponding substituted products in good yields. Notably, this reaction proceeded smoothly even from α-alkoxy-α-alkyl oxime acetates.Key words Beckmann fragmentation; phosphonium salt intermediate; Grignard reagent; carbon-carbon bond formationWe recently found that the treatment of acetals with a combination of trifluoromethanesulfonic acid trialkylsilyl ester (R 3 SiOTf) and base (e.g., pyridinium-type bases or triarylphosphines) gave the corresponding electrophilic pyridinium or phosphonium salts as stable intermediates. We subsequently showed that these salts can be used as stable synthetic equivalents of oxonium ions from acetals, and went on to develop a series of acetal substitution reactions using a variety of different nucleophiles (Eq. 1).1-10) One of the main advantages of our new methods is that the nucleophiles can be added to the reaction mixture long after the formation of the intermediate salts. Furthermore, these methods are compatible with a wide variety of nucleophiles, including acid and base labile nucleophiles. It is noteworthy that acid labile nucleophiles cannot normally be used in the reactions of oxonium ions, because oxonium ions are usually formed under Lewis acidic conditions in the presence of a nucleophile, which would preclude the use of an acid labile nucleophile. 11) We subsequently investigated the application of this salt chemistry to another reaction involving sequential Beckmann fragmentation/carbon-carbon (C-C) bond forming reactions, which has been previously reported by our group using organoaluminum reagents.12-15) The treatment of α-alkoxy oxime acetates with trifluoromethanesulfonic acid trimethylsilyl ester (TMSOTf) and 2,4,6-collidine produced the corresponding collidinium salt intermediates, which were successfully subjected to a C-C bond forming reaction with a variety of different Gilman reagents (Eq. 2).16) Gilman reagents were found to be the best type of organometallic carbon nucleophile for this reaction, with several other more popular organometallic reagents, including organolithium and Grignard reagents, failing to provide good results. However, we previously found that the phosphonium salts derived from O,O-acetals and (o-tol) 3 P reacted smoothly with Grignard reagents. [8][9][10] We therefore envisioned that the formation of a phosphonium salt instead of a collidinium salt would make it possible to use Grignard reagents in this reaction, which would represent a significant improvement over our previous method in terms of its scope and convenience.

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Organic synthesis based on the Beckmann fragmentation: generation of an electrophilic salt intermediate and successive C–C bond formation using Gilman reagents

Cited by 7 publications

References 17 publications

Highly Discriminative and Chemoselective Deprotection/Transformations of Acetals with the Combination of Trialkylsilyl Triflate/2,4,6-Collidine

Highly Discriminative and Chemoselective Deprotection/Transformations of Acetals with the Combination of Trialkylsilyl Triflate/2,4,6-Collidine

Using Neighboring-Group Participation for Acyclic Stereocontrol in Diastereoselective Substitution Reactions of Acetals

Beckmann Fragmentation and Successive Carbon–Carbon Bond Formation Using Grignard Reagents <i>via</i> Phosphonium Salt Intermediates

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