Cyclic Β-keto Esters Research Articles

Selective Transformations of β-Keto Esters, Promoted by Dowex Basic Ion-Exchange Resins

Depending on the nature of the Dowex basic ion-exchange resin, cyclic β-keto esters 1 react with α,β-unsaturated aldehydes 2 to give either the corresponding Michael adducts 3 or the highly functionalized bicyclo[3.3.1]nonanes 4 in a one-pot Michael addition−intramolecular aldolization sequence. Some selective transformations of the highly functionalized systems 3 and 4 to provide amino azabicyclo[3.3.1]nonanones 9, polycyclic aminals 10, and azacyclooctene 12 are also presented. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Environmentally friendly TPDS-mediated free radical ring expansion of α-haloalkyl cyclic β-keto esters

Reactivities of tetraphenyldisilane (TPDS), tris(trimethylsilyl)silane, and tributyltin hydride in the radical ring expansion of α-haloalkyl cyclic β-keto esters were examined. Among these reagents, TPDS was found most effective for the preparation of medium-sized cyclic compounds in terms of yields and ring-expansion/reduction selectivity.

Common synthetic strategy for optically active cyclic terpenoids having a 1,1,5-trimethyl- trans-decalin nucleus: syntheses of (+)-acuminolide, (−)-spongianolide A, and (+)-scalarenedial

We have developed a simple and practical method for providing enantiomerically pure bi-, tri-, and tetracyclic frameworks having a 1,1,5-trimethyl-trans-decalin nucleus, and demonstrated their utility for terpenoid synthesis. Thus, we achieved the stereocontrolled total syntheses of (+)-acuminolide as a bicyclic, (−)-spongianolide A as a tricyclic, and (+)-scalarenedial as a tetracyclic terpenoid from the corresponding optically pure cyclic β-ketoesters, which were obtained by repeating the same method of the ring construction, including the olefin cyclization with Lewis acid, followed by simple optical resolution using chiral auxiliaries for acetal formation, respectively. This is a general and valuable strategy for the synthesis of enantiomerically pure cyclic terpenoids having the 1,1,5-trimethyl- trans-decalin nucleus.

A New Sulfenylation Reagent, 3-Phenylsulfenyl-2-(N-cyanoimino)thiazolidine, and Its Optically Active Version

We have developed a new sulfenylation reagent, 3-phenylsulfenyl-2-(N-cyanoimino)thiazolidine 3, that is readily available and stable upon storage. Compound 3 easily reacts with amines or thiols to give the corresponding sulfenamides or asymmetrical disulfides in excellent yields. It was also found that the α-sulfenylation reaction of carbonyl compounds with 3 proceeds smoothly. Furthermore, optically active 4-diphenylmethyl derivative 4 was synthesized as an asymmetric sulfenylation reagent, which realized 96% e.e. upon α-sulfenylation of a cyclic β-keto ester.

Bicycloannelation Reaction of γ-Substituted Cyclic β-Ketoesters

The effect of y-substituants on the bicycloannelation of cyclic P-ketoesters in presence of Pd and 1,3-allylic diacetate is described.

Synthesis of vinyl nonaflates derived from β-ketoesters, β-diketones or α-diketones and their palladium-catalyzed cross-coupling reactions with organozinc halides

Cyclic and acyclic β-ketoesters 4, a typical cyclic α-diketone 5 and a typical cyclic β-diketone 6 were converted to the corresponding vinyl nonaflates of general formula 7, 8 and 9, respectively, by reaction with 1.2–1.5 equiv of NaH in DMF at 20–55 °C followed by treatment with 1.15–1.30 equiv of perfluoro-1-butanesulfonyl fluoride at 20 °C. These vinyl nonaflates, which were purified by MPLC on silica gel, proved to be excellent electrophiles in Pd-catalyzed cross-coupling reactions with aryl-, 1-alkynyl- and alkylzinc chlorides. A variety of cyclic and acyclic tetrasubstituted α,β-unsaturated esters which included stereoisomerically pure compounds, a 2-substituted 3-aryl-2-cyclopentenone and naturally-occurring dihydrojasmone were cleanly synthesized by these smooth and selective cross-coupling reactions.

Synthesis and reactivity of Michael adducts of cyclic β-ketoesters enolates with electrophilic acetylenes

The enolates of cyclic β-ketoesters react with electrophilic acetylenes to give the corresponding Michael adducts in good yields when the reaction is performed in acetone in the presence of catalytic amounts of K 2CO 3. The Michael adducts resulting from ethynylmethylketone, when refluxed in toluene in the presence of catalytic amounts of pTsOH, undergo an intramolecular aldol reaction leading mainly to bicyclo [n. 3. 1]alkadienones besides Robinson annulation products.

Microbial reduction of varying size cyclic β-ketoesters. : Stereoselective synthesis of chiral lactones and epoxides

The reduction of four- to eight-membered cyclic β-ketoesters to the corresponding β-hydroxyesters by various yeasts and fungi is described. The microbial reduction of ethyl cyclobutanone 2-carboxylate is reported for the first time. The different stereospecificities observed in these reductions involving a dynamic kinetic resolution are analysed. The enantiopure reduction products have been used in the synthesis of both enantiomers of functionalized lactones and epoxides.

First example of samarium diiodide-promoted sequential cyclization and ring-expansion reactions of α-bromomethyl cyclic β-keto esters to homologated γ-keto esters

SmI 2 reductions of some aromatic as well as aliphatic α-bromomethyl cyclic β-keto esters produced one-carbon homologated γ-keto esters in modest to good yields. Graphic

A Useful Oxidation Procedure for the Preparation of 3-Alkanoyltetronic Acids

An easy and convenient synthesis of 3-alkanoyl-5-hydroxymethyltetronic acids, the salts of which have inhibitory activity against HIV-1 protease, is described and a new direct route to 1,3-dicarbonylester from cyclic β-ketoester is developed.

Síntese de β-cetoésteres cíclicos: novo procedimento para ciclizações de Dieckmann empregando ALCL3 e trietilamina

In this communication we describe a new methodology to Dieckmann cyclization of diethyl adipate (1) and diethyl pimelate (3) applying push-pull strategy using anhydrous aluminium trichloride and triethylamine in dichloromethane at room temperature. This method is very efficient, simple, safe and reproducible, giving the corresponding cyclic β-keto ester derivatives in 84% and 71% yield, respectively.

Mechanism of Anionic Polymerization of (Meth)acrylates in the Presence of Aluminium Alkyls IV. Formation of a Co-ordinative Polymer Network via the Living Aluminate End Group

The polymerization of methyl methacrylate in the presence of aluminium alkyls in toluene deviates from conventional kinetics. This results predominantly from the formation and precipitation of a co-ordinative polymer gel or network. Due to the lower reactivity and accessibility of the living chains in the gel, they are regarded as ’dormant’ and thus the concentration of active species decreases during polymerization. The network formation occurs via co-ordination of the living aluminate chain end group with in-chain ester carbonyl groups. Part of the chains are deactivated by a termination process but they are free of cyclic β-ketoesters which would result from the common ’back-biting’ reaction.

Selective synthesis of 1-, and 3-carbomethoxy 2-tetralol stereoisomers by microbial reduction of the corresponding tetralones

The microbial reduction of β-ketoesters derived from 2-tetralone has been shown to produce good yields of 2-hydroxy-1-car☐y- or 3-hydroxy-2-car☐yesters. Baker's yeast invariably affords a high enantiomeric purity cis-hydroxyester, while fungi strains may produce, sometimes exclusively, cis- or trans- complementary stereochemistries. From a general survey of the baker's yeast reduction of cyclic β-ketoesters, a working model for predicting enantio- and diastereoselectivities of the reduction is proposed and discussed.

Use of Cyclic β-Keto Ester Derivatives in Photoadditions. Synthesis of (±)-Norasteriscanolide

The [2 + 2] photoaddition of 2-cyclopentenones with derivatives of the cyclic β-keto ester 1 was investigated. The resultant adducts then underwent fragmentation to 5/8 fused ring systems present in terpenoid natural products such as asteriscanolide (3). For example, photoaddition of 2-cyclopentenone with the trimethylsilyl derivative 13 gave the head-to-head cis-anti-cis adduct 14. Monomethylation and borohydride reduction of the adduct yielded lactone 19. Cleavage of the silyl ether in 19 with fluoride ion followed by spontaneous fragmentation gave norasteriscanolide (20). Substrate 20, which possesses all the stereochemical features of the natural product 3 but lacks two methyl groups, was synthesized in only four steps using this methodology.

Biotransformation of cyclic β-keto esters by Chlorella pyrenoidosa Chick

Algal transformations of three cyclic β-keto esters, methyl 2-oxocyclopentanecarboxylate (MCPC), ethyl 2-oxocyclohexanecarboxylate (ECHxC), and methyl 2-oxocycloheptanecarboxylate (MCHpC) were photoautotrophically studied with an axenic strain of Chlorella pyrenoidosa Chick. The three cyclic β-keto esters were transformed in two manners; reduction of the carbonyl group to a hydroxy group and elimination of the alkoxycarbonyl group. The former reaction occurred more often than the latter. The cis/trans ratios of the resulting alcohols in MCPC, ECHxC and MCHpC were 13 : 87, 15 : 85, and 65 : 35, respectively. The alkoxycarbonyl group elimination products were as follows: cyclopentanone and cyclopentanol in MCPC, cyclohexanone and cyclohexanol in ECHxC, and cycloheptanone in MCHpC.

Reactions of cyclic β-keto esters and other enol derivatives with 3-acetoxyamino-2-isopropylquinazolin-4(3H)-one: further oxidation of the cyclic α-(3,4-dihydro-2-isopropyl-4-oxoquinazolin-3-yl)amino ketones with lead tetraacetate leading to ring-expansion (in dichloromethane) and ring-cleavage (in methanol)

The cyclic β-keto esters 12, 20, 22, 26, the β-diketone 28 and the enol silyl ethers 24 and 30 have been converted in 60–77% yields into the corresponding α-(oxoquinazolinyl)amino cyclic ketone derivatives 16, 21, 23, 29, 27, 25 and 31, respectively, by reaction with 3-acetoxyamino-2-isopropylquinazolin-4(3H)-one 11. Further oxidation of some of these products with lead tetraacetate gives products whose nature depends on the solvent used; in dichloromethane, 16, 21 and 25, which contain 5-membered ring ketones, give ring-expanded products 32, 38 and 39, respectively whereas, in methanol, ring-cleavage of 16, 25 and 27 occurs to give imino-esters 41, 44 and 42/43, respectively. Ring-expansion of 23, 27 and 31, which contain 6-membered ring ketones, does not occur and the only isolated product in each case is the benzoxazinone 40. A mechanism which accounts for this dependence on the solvent is presented: radical intermediates do not appear to be implicated.

An unprecedented DBU–MeOH promoted one-pot γ-arylidenation of cyclic β-ketoesters by a directed γ-aldol reaction and dehydration sequence

Cyclic β-ketoesters 1 undergo, in a one-pot process, an unprecedented DBU–MeOH promoted selective γ-arylidenation with aldehydes 2, by a directed γ-aldol reaction and dehydration sequence, to afford stereoselectively synthetically valuable cycloalkenones 3 in good yields.

Facile Tandem Michael Addition-Retro Dieckmann Reaction of Cyclic β-Ketoesters: One-Pot Preparation of Polyfunctionalized Acyclic Derivatives

Abstract A facile base promoted tandem Michael addition-retro Dieckmann reaction leading to polyfunctionalized acyclic derivatives is observed by condensation of β-ketoesters with α,β-unsaturated electrophiles in methanol.

Preparation of cyclic α-(3,4-dihydro-2-isopropyl-4-oxoquinazolin-3-yl)amino-β-ketoesters: Further oxidation with lead tetra-acetate in dichloromethane and in methanol leading to ring-expansion and ring-cleavage products, respectively

Cyclic β-ketoesters e.g. 7 and the enol silyl ether 18 are converted to the corresponding α-(quinazolinonyl)amino (α-Q′NH) derivatives 10 and 19 respectively by reaction with the 3-acetoxyaminoquinazolinone 6: further oxidation of 10 and 19 with lead tetra-acetate in dichloromethane gave ring-expanded products 15 and 20 respectively but with methanol as solvent the corresponding ring-cleaved products 21 and 22 are obtained: radical intermediates do not appear to be involved.

Oxidative cleavage of 2-substituted cycloalkane-1,3-diones and of cyclic β-ketoesters by copper perchlorate / oxygen

A preparative method for the synthesis of (ω-1), ω-dioxocarboxylic acids and (ω-1)-oxoalkanedioic acids monoesters by respective oxidative cleavage of 2-substituted cycloalkane-1,3-diones and cyclic β-ketoesters, by copper perchlorate in acetonitrile in an oxygen atmosphere, is reported.