Michael Cyclization Research Articles

Total synthesis of tricyclic β-lactams

The synthesis of tricyclic carbapenam and penems was achieved by highly stereoselective Lewis acid-catalyzed reactions of 4-substituted 1-trimethylsilyloxyfurans with a 4-acetoxy azetidinone chiron, and further elaboration of the resulting condensation products using intramolecular Michael cyclizations.

Synthesis of Carbacephems from Serine

Carbacephems have been synthesized from d-serine by two routes involving construction first of the six-membered ring followed by cyclization to give the bicyclic β-lactam. In one route, alkylation of a lactim ether was accomplished with Ni(Acac)2 as a catalyst. The desired R stereochemistry at the carbon corresponding to C-6 of the cephem was obtained by stereospecific hydrogenation of a vinylogous carbamate. The second route involved a stereospecific Michael cyclization to give the same C-6 stereochemistry. Closure of a piperidyl β-amino acid intermediate common to both routes was accomplished using a modified Mukaiyama reagent found to be superior in our system to the traditional reagent. The resulting carbacephem core was stereospecifically substituted at C-7 with an ethyl or amino functionality. The ethylated intermediate was transformed into a stable enol triflate useful for the further elaboration of biologically important carbacephems.

ChemInform Abstract: Formation of Highly Substituted Cyclopentanes from Radical and Anionic Michael Cyclizations of α‐Iodo‐γ‐ and ‐δ‐lactones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Unprecedented formation of spirobicyclo[3.1.0]hexanes through tandem acetylene-addition - Michael cyclization

Reaction of 4-pentynyltriphenylphosphonium bromide 2 with oestrone methyl ether in the presence of potassium tert-butylate produced a spirobicyclo[3.1.0]hexane rather than the anticipated Wittig product. The reaction appears to be general for pinacolone-type ketones, as was demonstrated by several examples. A mechanism for this anomalous reaction is proposed.

Stereoselective synthesis of cis-decalins via Diels–Alder and double Michael addition of substituted Nazarov reagents

The base-catalyzed cycloaddition and double Michael cyclization of substituted Nazarov reagents and of 1-phenylsulfinyl analogs, with 2-carbomethoxy-2-cyclohexen-1-one 1 yielding cis-decalins is reported. The reaction is highly stereoselective affording cis,cis- or cis, trans-decalins. Mechanistic aspects are briefly discussed.

(±)-2-amino-2-thiazoline-4-ethanoic acid; a novel, specific GABA A receptor agonist

Intramolecular Michael cyclization led directly to-amino-2-thiazoline-4-ethanoic acid, a new and potent member of the limited group of specific GABA A receptor agonists.

A novel ring-closure strategy for the carbapenems: the total synthesis of (+)-thienamycin

Intramolecular Michael cyclization of an N-[(alkoxycarbonyl) methyl]-4-(3-nitro-2-propenyl)-3-oxoazetidin-2-one available in optically pure form leads to the corresponding carbapenam skeleton. Further elaboration via oxidative cleavage of an exocyclic nitromethylene group gives an advanced intermediate, which was transformed into (+)-thienamycin. The stereochemistry of the Michael cyclization and the pitfalls of protective group chemistry are discussed

Highly stereoselective double michael cyclization of 1-phenylsulfinyl and sulfonyl analogues of the nazarov reagent

The base-catalyzed double Michael addition of the β-keto sulfoxide 5 with 2-carbomethoxy-2-cyclohexenone ( 1) proceeds, after elimination of the sulfoxide moiety during chromatography on silica, to give the dehydrodecalin adduct 6 with high stereoselectivity.

ChemInform Abstract: A Novel Synthetic Route to the Hexahydrobenzofuran Subunit of the Avermectins and Milbemycins.

Abstract2‐Acetoxyfuran (I) is coupled with maleic anhydride (II) to give the anhydride (III).

ChemInform Abstract: Regioselective Synthesis of the Spiro‐benzofuran Unit, Present in Several Natural Products, by an Intramolecular Michael Cyclization.

AbstractA spiro‐benzofuran unit, as shown in compounds (VI) and (VII), is common to several biologically active natural products.

ChemInform Abstract: Regioselective Synthesis of the Spiro‐benzofuran Unit, Present in Several Natural Products, by an Intramolecular Michael Cyclization.

AbstractDas ausgehend vom Ketoester (I) über den ogß‐ungesättigten Aldehyd (IIIc) gemäß Schema hergestellte Enon (VII) liefert nach Etherspaltung mit Bortribromid über eine intramolekulare Michael‐Addition ein chromatographisch trennbares Gemisch der beiden isomeren Spirobenzofurane (VIII) und (IX) sowie des Enons (X).

Regioselective Synthesis of the Spiro-Benzofuran Unit, Present in Several Natural Products, by an Intramolecular Michael Cyclization

Abstract The regioselective construction of a spirocycle unit, common to several biologically active natural products, through an intramolecular Michael cyclization is described.

Regioselective Synthesis of the Spiro-benzofuran Unit, Present in Several Natral Products, by an Intramolecular Michael Cyclization

Abstract The regioselective construction of a spirocycle unit, common to several biologically active natural products, through an intramolecular Michael cyclization is described.

Promising cyclization reactions to construct the ring systems of brevianamides A,B

An effective intramolecular Michael cyclization and intramolecular SN 2′ cyclization is described for constructing the tricyclic framework of the natural mycotoxins brevianamides A,B.

A novel synthetic route to the hexahydrobenzofuran subunit of the avermectins and milbemycins

Radical-induced intramolecular Michael cyclization of a bromovinyl-type appendage onto a functionalized cyclohexene carboxylic acid derivative produces the corresponding oxahydrindanes which can be transformed into oxahydrindenes (hexahydrobenzofurans) related to the title compounds. (−)-Quinic acid is a useful optically active precursor.

Total synthesis of antitumor agent at-125, (α S,5 S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid

A short and efficient total synthesis of racemic AT-125 and its racemic threo isomer proceeds via an intramolecular Michael cyclization of a protected α,β-dehydroglutamic acid γ-hydroxamate. Separation of diastereomers and deprotection to racemic AT-125 followed by enzymatic resolution of the N-chloroacetamide with hog-kidney acylase provides the natural α S,5 S isomer.

Synthetic entry to the hexacyclic Aspidosperma alkaloids. Total synthesis of (±)-4-hydroxyaspidofractinine

The pentacyclic intermediate (V) underwent a new type of Michael cyclization on the vinylogous amide system with acrylonitrile and methyl vinyl sulphone to give regio- and stereo-specific bridge formation producing the hexacyclic compounds which constitute the aspidofractinine (I) skeleton.