Conversion of 2-Alkyl-2-(2-oxopropyl)cyclopentane-1,3-diones into 2,3,5- and 2,3,4-Trisubstituted Cyclopent-2-enones by Intramolecular Aldolizations to 2,3-Diacylcyclopropanolates Followed by Remarkable Skeletal Rearrangements¹

Abstract

2-Alkyl-2-(prop-2-ynyl)cyclopentane-1,3-diones 2, conveniently prepared from 2-alkylcyclopentane-1,3-diones 1 and prop-2-ynyl bromide, afford the triketones 3 by Hg2+-catalyzed hydration of the acetylenic triple bond. Treatment of these triketones with aqueous sodium hydroxide gives rise to the 2,3,5-trisubstituted cyclopent-2-enones 5, which are accompanied by the isomeric 2,3,4-trisubstituted cyclopent-2-enones 7 as byproducts. The formation of these isomers can be avoided, when the 2,2-disubstituted cyclopentane-1,3-diones 2 are first converted by ring cleavage into the 5-alkyl-4-oxooct-7-ynoic acids 4 and then by subsequent hydration into the 5-alkyl-4,7-dioxoalkanoic acids 6. An intramolecular aldolization of the latter forms exclusively the cyclopentenones 5. A mechanism explaining the simultaneous formation of 5 and 7 from 3 is based on the formation of the 2,3-diacylcyclopropanolates 11 and 16 by intramolecular aldolization and subsequent ring opening to the 2-acetylcyclohexane-1,4-diones 13 and 18. A further ring opening to the 4,7-dioxoalkanoates 15 and 20 followed by intramolecular aldol condensation then gives rise to the isomeric trisubstituted cyclopent-2-enones 5 and 7.

Catalytic Hydration of Alkynes and Its Application in Synthesis

“…56 For mercury(II) in general, catalyst loadings from 0.1 mol% to excess (≥250 mol%) have been reported, but the range of 2-10 mol% is more usual. Reaction temperatures range from -20°C 64 67 Phenylmercuric hydroxide has been proposed as a stoichiometric reagent for hydration of aliphatic, nonconjugated terminal alkynes. 68…”

“…Non-enolizable b-diketones 64 or b-keto esters or malonates 214 bearing an a-propargyl substituent are readily hydrated; the Hennion-Nieuwland acetalization catalyst has been used. 62a Unprotected carboxylic acids are also hydrated, 64,215 as are carboxylic acid esters. A fivemembered-ring lactone was hydrated to give either of two epimeric products, depending on the reaction conditions (Scheme 35).…”

Synthesis of Cyclopentitols by Ring-Closing Approaches

“…Cyclopentenones 360, possessing a carboxylic moiety in the side chain, have been prepared from the cyclic diketone 358 by successive alkylation, ring cleavage, hydration, and base-catalyzed intramolecular aldolization of thus obtained diketones 359 (Scheme 112). 394 When carrying out the aldolization via triketones 361, the authors have obtained the aldol products 362 along with the isomeric cyclopentenones 363 as byproducts. The proposed mechanism, involving deprotonation, nucleophilic attack with ring enlargement, alkali-promoted ring opening, and condensation to cyclopentenone, was confirmed by the isolation of the sixmembered cyclic intermediate by acidification.…”

“…Cyclopentenones 360 , possessing a carboxylic moiety in the side chain, have been prepared from the cyclic diketone 358 by successive alkylation, ring cleavage, hydration, and base-catalyzed intramolecular aldolization of thus obtained diketones 359 (Scheme ) . When carrying out the aldolization via triketones 361 , the authors have obtained the aldol products 362 along with the isomeric cyclopentenones 363 as byproducts.…”

Ruthenium-Catalyzed Anti-Markovnikov Hydration of Terminal Alkynes

“…Reaction temperatures range from -20 °C to reflux temperature of the organic solvent. 53 Reaction times vary from minutes to a day and catalyst loadings from 0.1 mol-% to excess (≥250 mol-%), though the range of 2-10 mol-% is more usual. Little improvement of the basic methodology has occurred except for the introduction by NISHIZAWA of Hg(OTf) 2 •2TMU in MeCN/CH 2 Cl 2 as efficient catalyst at room temperature.…”