Heterocyclic Intermediates Research Articles

ChemInform Abstract: Asymmetric Syntheses via Heterocyclic Intermediates. Part 36. Asymmetric Synthesis of Dimethyl (R)‐4‐Amino‐4‐methyl‐2‐pentenedioates (Dimethyl β,γ‐Didehydro‐α‐methyl‐D‐glutamates) or Methyl (R)‐2,5‐Dihydro‐2‐methyl‐5‐oxo‐2‐pyrrolecarboxylates by the Bislactim Ether Method. ‐ Asymmetric Synthesis of β,γ‐Didehydroglutamic Acids.

AbstractThe (in situ) lithiated bis‐lactim ether (Ia) reacts with the methyl acrylates (II) or (IV) to give the "Michael adducts" (III) or (V) with a high degree of asym.

ChemInform Abstract: Asymmetric Synthesis via Heterocyclic Intermediates. Part 1. Synthesis of 3,4‐Dihydro‐11a‐(S)‐methyl‐4‐(R)‐phenyl‐1,4‐oxazino(4,3‐b)isoquinolin‐1(6H,11H)‐one (III).

ChemInform Abstract: Asymmetric Synthesis via Heterocyclic Intermediates. Part 1. Synthesis of 3,4‐Dihydro‐11a‐(S)‐methyl‐4‐(R)‐phenyl‐1,4‐oxazino(4,3‐b)isoquinolin‐1(6H,11H)‐one (III).

ChemInform Abstract: Ketene‐S,N‐acetals as Synthetic Intermediates for Heterocycles. New Synthesis of Multisubstituted Pyridine‐2‐thiones.

AbstractCoupling of malodinitrile (II) with the ketene‐S,N‐acetals (I) and (V) yields the β‐dicyanomethylene thioamides (III) and (VI) which are cyclized under basic conditions to form the pyridinethiones (IV) or (VII).

Stereocontrolled reactions through heterocyclic intermediates

Abstract

Asymmetric synthesis via heterocyclic intermediates - XXXIX 1: Asymmetric synthesis of (enantiomerically and diastereomerically virtually pure) methyl 2-amino-4,5-epoxy-3-hydroxy-alkanoates and methyl 2-amino-3-hydroxy-4,5-methylene-alkanoates by the bislactimether method

α,β-Unsaturated aldehydes react with the titanated bislactin ether 6 of cyclo-(L-val-gly) to give the (2R,1'S)-syn-addition products of type 8 . With TBHP (catalyzed by Ti(OiPr) 4 with and without (+) - or (-) -DET) these furnish the epoxides 10 or 11 with 1', 2' -anti or 1', 2'-syn relation. In some cases virtually only one stereoisomer is formed. Upon acid hydrolysis the compounds 10 or 11 give the corresponding methyl (2R,3R)-2-amino-4,5-epoxy-3-hydroxy-alcanoates (type 12 or 13 ). As experiments with 10c revealed, the oxirane ring in 10 or 11 can be submitted to various regio- and stereo-controlled transformations affording the precursors of type 14 or 17 of amino acids in the sugar series. Cyclopropanation of 8 (diiodo methane/diethyl zinc) proceeds highly diastereoselectively to give the cyclopropanes of type 19 . Upon acid hydrolysis these give the corresponding (enantiomerically and diastereomerically pure) methyl (2R,3S,4R,5R)-2-amino-3-hydroxy-4,5-methylene-alcanoates of type 20 .

Asymmetric Synthesis via Heterocyclic Intermediates; XXXVII1Asymmetric Synthesis of Dimethyl (R)-2-Amino-(E)-hept-4-enedioates by the Bislactim Ether Method

An asymmetric synthesis of (virtually enantiomerically and diasteriomerically pure) dimethyl (2R, 3?)-2-amino-(E)-heptene-1,7-dioates of type 9 is described.

ChemInform Abstract: Ketene S,N‐Acetals as Synthetic Intermediates for Heterocycles. Reaction of Ketene S,N‐Acetals with 1,4‐Quinones.

AbstractAnellation of the quinones (I) or (IV) with the ketene S,N‐acetals (II) yields the furans (III) or (V) bearing enamine groups.

ChemInform Abstract: Asymmetric Syntheses via Heterocyclic Intermediates. Part 35. Optically Active α‐Arylglycine Esters by Friedel‐Crafts Alkylation with the Chiral Cation of the Bislactim Ether of cyclo‐(L‐Val‐Gly).

AbstractArylation of the chiral bislactim chloride (I) yields diastereomeric mixtures of the aryldihydropyrazines (III) and (IV) (in the case of (IIIc) and (IVc) additionally minor amounts of the 2‐methoxyphenyl substituted regioisomers are formed); hydrolysis of the major isomers (IIIa)‐(IIIc) affords the (R)‐configurated arylglycine esters (V).

ChemInform Abstract: Asymmetric Syntheses via Heterocyclic Intermediates. Part 34. Asymmetric Synthesis of α‐Amino‐γ‐nitrocarboxylic Esters by the Bislactim Ether Method.

AbstractMetalation of the ether (S)‐(I) followed by reaction with the alkenes (II) yields the products (III) with 97‐99% stereoselectivity.

ChemInform Abstract: Asymmetric Syntheses via Heterocyclic Intermediates. Part 33. Asymmetric Synthesis of (Diastereomerically and Enantiomerically Virtually Pure) Methyl (2R,3S)‐threo‐2‐Amino‐3‐hydroxy‐4‐alkenoates by the Bislactim Ether Method.

AbstractThe titanium derivative (III) of the bislactim ether (I) from cyclo(Val‐Gly) reacts with unsaturated aldehydes (IV) exclusively by 1,2‐addition in a highly diastereoselective mode to give the products (V).

Asymmetric synthesis via heterocyclic intermediates. I. Synthesis of 3,4‐dihydro‐11a‐(S)‐methyl‐4‐(R)‐phenyl‐1,4‐oxazino[4,3‐b]isoquinolin‐1(6H,11H)‐one

AbstractThe synthesis of 3,4‐dihydro‐11a‐(S)‐methyl‐4‐(R)‐phenyl‐1,4‐oxazino[4,3‐b]isoquinoline‐1(6H,11H)‐one 1 is described.

ChemInform Abstract: Asymmetric Syntheses via Heterocyclic Intermediates. Part 32. Asymmetric Synthesis of Cyclic α‐Amino Acids by the Bislactim Ether Method.

AbstractThe bislactim ether (I) reacts with the dibromides (II) to give the bromides (III), which are cyclized to the bicyclic compounds (IV).

Asymmetric Syntheses via Heterocyclic Intermediates, XXXIII. Asymmetric Synthesis of (Diastereomerically and Enantiomerically Virtually Pure) Methyl (2R,3S)‐threo‐2‐Amino‐3‐hydroxy‐4‐alkenoates by the Bislactim Ether Method

AbstractThe titanium derivative 4a of the bislactim ether 1a from cyclo‐(L‐Val‐Gly) reacts with α,β‐unsaturated aldehydes 5 exclusively by 1,2‐addition in a highly diastereoselective mode to give virtually only the (2R,1′S) diastereomers of type 6. Upon hydrolysis these furnish the methyl (2R,3′S)‐threo‐2‐amino‐3‐hydroxy‐4‐alkenoates of type 11–13 which are essentially diastereomerically and enatiomerically pure.

ChemInform Abstract: Asymmetric Syntheses via Heterocyclic Intermediates. Part 31. Asymmetric Synthesis of Various Non‐Proteinogenic Amino Acid Methyl Esters (Functionalized in the Carbon Chain) and Amino Acids by the Bislactim Ether Method.

AbstractThe bislactim ethers (II), (VI), (X) and (IVa) are converted to their lithiated derivatives (III), (VII), (XI) and (XIV).

ChemInform Abstract: Asymmetric Synthesis via Heterocyclic Intermediates. Part 30. Asymmetric Synthesis of Glutamic Acids and Derivatives thereof by the Bislactim‐ether Method. Michael‐Addition of Methyl 2‐Alkenoates to the Lithiated Bislactim‐ether of Cyclo‐(L‐Val‐Gly).

AbstractThe lithiated bislactim ether (II) is coupled with the methyl 2‐alkenoates (III) to yield the adducts (IV).

Asymmetric Synthesis via Heterocyclic Intermediates. Asymmetric Synthesis of (-)-(1S,2R)-Allocoronamic Acid

Asymmetric Synthesis via Heterocyclic Intermediates. Asymmetric Synthesis of (-)-(1S,2R)-Allocoronamic Acid

Ketene-S,N-acetals as synthetic intermediates for heterocycles. New synthesis of multisubstituted pyridine-2-thiones.

Ketene-S, N-acetals reacted with isothiocyanates to give β-aminothiocarbonyl-α-methylthioen-amines, which were transformed into enaminonitriles by carbon-carbon bond formation with malononitriles. Treatment of the enaminonitriles with base afforded pyridine-2-thiones. In addition, bis-lithio-ketene-S, N-acetals, generated from the enaminonitriles and n-BuLi, reacted with alkyl halides to give 3-alkylpyridine-2-thiones.

Ketene S,N-acetals as synthetic intermediates for heterocycles. Reaction of ketene S,N-acetals with 1,4-quinones

Annelation of ketene S,N-acetals with 1,4-quinones is found to give benzo[b]- and naphtho[1,2-b]furans bearing enamine groups. Subsequent enamine reaction allows the formation of 1-benz- and naphtho[1,2-b]oxepines and benzofuran-2-ones.

Asymmetric syntheses via heterocyclic intermediates, XXXI. Asymmetric synthesis of various non‐proteinogenic amino acid methyl esters (functionalized in the carbon chain) and amino acids by the bislactim ether method

AbstractThe lithiated bislactim ethers 5, 10, 12, and 23 were alkylated with a variety of alkylating agents 6 to give the alkylated bislactim ethers 7, 11, 13, and 24 with a high degree of asymmetric induction (up to 99%). Upon hydrolysis these furnished the optically active amino acid methyl esters of type 8, 14, or 25. Some of these amino acid esters were further hydrolyzed to yield the amino acids.

ChemInform Abstract: Thioketone‐S‐oxides by [2 + 2] Cycloaddition of Ynamines with N‐Sulfinyl‐tosylamide.

AbstractThe title reaction yields the heterocyclic intermediates (III), which isomerize to give either E or Zproducts (IV) [E‐(IVc) converts to Z‐(IVc) in solution].