A Simple Preparation of 2-Silylated 3-Furoic Acids and 2-Silylated 3-Thiophenecarboxylic Acids

Beese, G.; Keay, Brian A.

doi:10.1055/s-1991-20618

Cited by 22 publications

(6 citation statements)

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“…Although the ratio of isomers formed in the Gewald reaction could not be improved, a simple wash procedure was developed that allowed removal of the ethyl isomer 2a with a tolerable recovery of the desired isomer 2b . The Discovery chemists 3 found that the silyl group could be put in through a deprotonation process rather than the halogen−metal exchange originally used. This reaction with lithium diisopropylamide (LDA) as the base could be run at 0 °C as opposed to −70 °C, and eliminated the difficult-to-handle bromo acid as an intermediate.…”

Section: Resultsmentioning

confidence: 99%

Process Research on the Synthesis of Silthiofam: A Novel Fungicide for Wheat

Phillips¹,

Fevig²,

Lau³

et al. 2002

Org. Process Res. Dev.

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The development of an efficient, low-cost synthesis of the novel wheat fungicide silthiofam (1) is described. Improvements to the original Discovery route allowed 300 kg of material to be prepared in two, overlapping pilot-plant campaigns. Thereafter, efforts were focused on further optimizing the pilot-plant route, and on devising alternate, lower cost routes to silthiofam. One potential new route involved a cycloaddition reaction between 3-mercapto-2-butanone and N-(2-propenyl)-3-trimethylsilylpropynamide. The cyclic product could be directly dehydrated to silthiofam, however the overall yield was modest, raw material costs were high, and there were purification problems. The route ultimately selected for development proceeds in 6 chemical steps and about 60% yield from the inexpensive precursors 3-chloro-2-butanone and methyl 3-methoxyacrylate. Key features of the route are a novel thiophene-3-carboxylate synthesis involving cycloaddition of 3-mercapto-2-butanone with the acrylate followed by acid catalyzed aromatization, the room temperature formation and silylation of a thiophene-3-carboxylate dianion, and conversion of the resulting carboxylic acid into silthiofam with negligible loss of the silyl group. The process involves isolation of just two intermediates, only one of which is purified, and uses only three organic solvents, all of which are recycled. It can be run safely on large scale to give high-purity silthiofam.

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Section: Resultsmentioning

confidence: 99%

Process Research on the Synthesis of Silthiofam: A Novel Fungicide for Wheat

Phillips¹,

Fevig²,

Lau³

et al. 2002

Org. Process Res. Dev.

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“…3-Carboxy furans and thiophenes can be deprotonated and silylated at the 2-position either via the ester monoanion or the carboxylate dianion (Scheme 158). [285][286][287]…”

Section: Scheme 157mentioning

confidence: 99%

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

Sommer¹

2004

Synthesis

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The replacement of a b-hydrogen on an a,b-unsaturated carbonyl system with a non-hydrogen, non-carbon atom amounts to either a net two electron oxidation or an isohypsic substitution at the b-carbon. The resulting compounds are the functional equivalents of b-dicarbonyl derivatives. Although many methods have been developed to effect this transformation, they lack generality and the process remains an underutilized one in organic synthesis.

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“…In this and the following paper, we provide a full account of our work on the silyl migrations and regioselective lithiations. This paper will provide a full account of (a) the [1,4] O → C silyl rearrangement of 3-((silyloxy)methyl)furans and -thiophenes, (b) the [1,4] O → C silyl migration of silyl esters of 3-furoic acid and 3-thiophenecarboxylic acids; and (c) the [1,4] C → O silyl rearrangement of 2-silylated-3-(hydroxymethyl)-4-substituted furans and thiophenes …”

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confidence: 99%

Regioselective Preparation of 2,4-, 3,4-, and 2,3,4-Substituted Furan Rings. 1. [1,4] O → C and [1,4] C → O Silyl Migrations of Silyl Ethers and Esters Attached to Furan and Thiophene Rings

et al. 1997

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1,4] O f C and [1,4] C f O rearrangements are described for a variety of furans and thiophenes. Treatment of 3-((silyloxy)methyl)furans and -thiophenes with n-BuLi in HMPA provided 2-silylated-3-(hydroxymethyl)furans and -thiophenes in good to excellent yields. The reaction was shown by crossover studies to proceed via an intramolecular [1,4] O f C silyl migration. Silyl esters of 3-furoic acids also underwent an intramolecular [1,4] O f C silyl migration to provide 2-silylated-3-furoic acids in moderate to good yield when treated with a mixture of LDA and HMPA. Finally, the above silyl migrations were shown to be reversible. Treatment of 2-silylated-3-(hydroxymethyl)furans and -thiophenes with NaH in DMF provided 3-((silyloxy)methyl)furans and -thiophenes in excellent yields via a [1,4] C f O silyl migration. The [1,4] C f O silyl migration was also shown to be an intramolecular process by a crossover study.

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A Simple Preparation of 2-Silylated 3-Furoic Acids and 2-Silylated 3-Thiophenecarboxylic Acids

Cited by 22 publications

References 0 publications

Process Research on the Synthesis of Silthiofam: A Novel Fungicide for Wheat

Process Research on the Synthesis of Silthiofam: A Novel Fungicide for Wheat

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

Regioselective Preparation of 2,4-, 3,4-, and 2,3,4-Substituted Furan Rings. 1. [1,4] O → C and [1,4] C → O Silyl Migrations of Silyl Ethers and Esters Attached to Furan and Thiophene Rings

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