31887-89-5

Upstream product

• 4471-09-4 N-benzylcyclohexylimine 
• 4594-78-9 cyclohexanone-2-propionitrile 
• 100-46-9 benzylamine 
• 1655-07-8 ethyl 2-oxocyclohexane carboxylate 
• 154819-92-8 1-Benzyl-2-oxo-1,3,4,5,6,7-hexahydro-2H-quinoline-4a-carboxylic acid ethyl ester 
• 108-94-1 cyclohexanone 
• 97022-10-1 3-(2-Pyrrolidin-1-yl-cyclohex-1-enyl)-propionic acid ethyl ester 

Relevant academic research and scientific papers

Synthesis of [6-6-6] ABE tricyclic ring analogues of methyllycaconitine

A new synthesis of the bridged [6-6-6] ABE tricyclic ring analogues of methyllycaconitine with the C-1 oxygenated substituents has been developed using an efficient aza-annulation of β-enamino ketone followed by a facile decarboxylation to form BE rings. Subsequent elaboration to form the A ring was achieved by a transannular acyl radical cyclization with concomitant equipment of the key C-1 oxygen functionality.

Ruthenium-Catalyzed Hydration of Nitriles and Transformation of δ-Ketonitriles to Ene-lactams: Total Synthesis of (-)-Pumiliotoxin C

Hydration of nitriles with 1-2 equivalents of water can be performed efficiently by using RuH2(PPh3)4 catalyst to give the corresponding amides.Under the similar reaction conditions, δ-ketonitriles can be converted into the corresponding ene-lactams, which are versatile synthetic intermediates.The efficiency of the reaction is demonstrated by the short-step synthesis of (-)-pumiliotoxin C.

Formation of 1,2,3,4-Tetrahydro-2-pyridones by Aza-Annulation of Imines with Acrylate Derivatives

The aza-annulation of imines with activated acrylate derivatives was studied as a means of preparing the corresponding 1,2,3,4-tetrahydro-2-pyridones.Through the use of reagents known to facilitate the formation of amide bonds from carboxylic acids, several methods of activating the acrylate species were compared.The acrylate derivatives studied were acryloyl chloride and acrylic anhydride as well as acrylic acid activated by reaction with EtO2CCl, (PhO)2P(O)N3, or MCPI.Optimum annulation was obtained with imines derived from cyclohexanone to produce octahydro-2-quinolone products.The N-isobutylimine prepared from cyclopentanone also produced selective ring annulation to efficiently produce the corresponding bicyclic product, but the reaction with the imine of n-butanal produced lower yields of cyclic product.Ring formation was relatively unaffected by substituents at the α-position of the acrylate derivative, demonstrated by the use of methacrylate, but β-substituents hindered the annulation process and, in turn, increased the amounts of byproduct resulting from only N-acylation of the imine.Increasing the steric bulk of the imine alkyl substituent produced the opposite effect; the relative amount of N-acylation compared to complete aza-annulation was diminished as the size of the substituent was increased.Mechanistic features of the reaction are discussed in terms of product distribution and competition experiments.

ENAMINE CHEMISTRY-XXIV. SYNTHESIS, THIATION, AND REDUCTION OF LACTAMS

Enamines, 1, prepared from cyclohexanones or cyclopentanones are reacted with acrylamide to give lactams, the condensed 2-piperidones, 2.Ethyl 2-(1-pyrrolidinyl)-2-cyclohexene-1-propanoate, 3, when treated with primary amines, produces the corresponding N-substituted 2-piperidones, 4.Ethyl 2-(1-pyrrolidinyl)-2-cyclohexene-1-ethanoates and ethyl 2-(1-pyrrolidinyl)-2-cyclopentene-1-ethanoate, 5, react with primary amines to give condensed N-substituted 2-pyrrolidones, 6, and non-cyclic imines, 7.The starting enamines , 1, treated with 2-bromo acetamides only afford the N-alkylated compounds, 8 (2-pyrrolidino acetamides), and the regioselectivity of this reaction is rationalized in terms of the HSAB-principle.Compound 1 undergoes an exchange reaction (aminolysis) when reacted with primary amines to give the imines 9.Thiation of the lactams 2 and 6 with the Lawesson reagent (LR), affords the corresponding thiolactams, 10.Reduction of the lactams and thiolactams, 2, 6, and 10 by LAH gives the imines, 11, and the enamines, 16.Further reduction of 11 (LAH) affords the saturated amines, 15.The stereochemistry for the formation of 15 is discussed using the torsion angle notation and the principal of least torsional distortion.In a one-pot reaction using LAH-acetic anhydride the lactams, 2, and the thiolactams, 10, are transformed into the enamides, 14.Compound 14 was also obtained from 11 by direct acetylation with acetic anhydride in the presence of triethylamine.