Lithium bromide-promoted three-component synthesis of oxa-bridged tetracyclic tetrahydroisoquinoline derivatives

Heating a toluene soln. of an alpha -(isocyano)acetamide deriv., an aldehyde and a 3-(2-aminophenyl)propenoic acid (aniline) deriv. in the presence of lithium bromide at 60 Deg provides an oxa-bridged tetracyclic tetrahydroquinoline in good to excellent yield as a mixt. of two separable diastereoisomers. In this one-pot multicomponent reaction, one C-N, one C-O and three C-C bonds are formed with concomitant creation of five asym. centers and three heterocycles. Fragmentation of epoxy-tetrahydroquinoline an under mild acidic conditions affords a 4,6-phenanthroline deriv. The multicomponent reaction of 2-isocyano-1-(4-morpholinyl)-3-phenyl-1-propanone with heptanal and 3-(2-aminophenyl)-2-propenoic acid Me ester gave (1R,2S,4aS,5S,10bS)-rel-5-hexyl-1,5,6,10b-tetrahydro-2-(4-morpholinyl)-3-(phenylmethyl)-2H-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylic acid Me ester (major product). [on SciFinder (R)]


Published in:
Heterocycles, 73, 729-742
Year:
2007
Keywords:
Addition reaction (nucleophilic; prepn. of (alkyl)tetrahydro(morpholinyl)-2 ; 4a-epoxybenzo[f][1 ; 7]naphthyridine-1-carboxylates via lithium bromide-promoted ; stereoselective Ugi three-component reaction of aldehyde ; (isocyano)(morpholinyl)alkanone ; (aminophenyl)propenoate); Stereoselective synthesis (prepn. of (alkyl)tetrahydro(morpholinyl)-2 ; 4a-epoxybenzo[f][1 ; 7]naphthyridine-1-carboxylates via lithium bromide-promoted Ugi three-component reaction of aldehyde ; (isocyano)(morpholinyl)alkanone ; (aminophenyl)propenoate); Aldehydes; Isocyanates Role: RCT (Reactant) ; RACT (Reactant or reagent) (prepn. of (alkyl)tetrahydro(morpholinyl)-2 ; 4a-epoxybenzo[f][1 ; 7]naphthyridine-1-carboxylates via lithium bromide-promoted Ugi three-component reaction of aldehyde ; (isocyano)(morpholinyl)alkanone ; (aminophenyl)propenoate); Diels-Alder reaction (prepn. of (alkyl)tetrahydro(morpholinyl)-2 ; 4a-epoxybenzo[f][1 ; 7]naphthyridine-1-carboxylates via lithium bromide-promoted ; stereoselective Ugi three-component reaction of aldehyde ; (isocyano)(morpholinyl)alkanone ; (aminophenyl)propenoate); Fragmentation reaction (prepn. of (alkyl)tetrahydro(morpholinyl)benzo[f][1 ; 7]naphthyridine-1-carboxylate via fragmentation of 2 ; 4a-epoxybenzo[f][1 ; 7]naphthyridine-1-carboxylate precursor); Multicomponent reaction; Ugi reaction (stereoselective; prepn. of (alkyl)tetrahydro(morpholinyl)-2 ; 4a-epoxybenzo[f][1 ; 7]naphthyridine-1-carboxylates via lithium bromide-promoted Ugi three-component reaction of aldehyde ; (isocyano)(morpholinyl)alkanone ; (aminophenyl)propenoate); Carboxylic acids Role: RCT (Reactant) ; RACT (Reactant or reagent) (alpha ; beta -unsatd. ; aminoaryl ; esters; prepn. of (alkyl)tetrahydro(morpholinyl)-2 ; 4a-epoxybenzo[f][1 ; 7]naphthyridine-1-carboxylates via lithium bromide-promoted Ugi three-component reaction of aldehyde ; (isocyano)(morpholinyl)alkanone ; (aminophenyl)propenoate) ; morpholine epoxybenzonaphthyridine carboxylate prepn stereoselective Ugi reaction lithium bromide; piperidine epoxybenzonaphthyridine carboxylate prepn stereoselective Ugi reaction lithium bromide
Note:
CAN 148:285131
28-13
Heterocyclic Compounds (More Than One Hetero Atom)
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
0385-5414
written in English.
3867-18-3 Role: RCT (Reactant), RACT (Reactant or reagent) (lithium bromide-promoted three-component synthesis of oxa-bridged tetracyclic tetrahydroisoquinoline derivs. (without concurrent Passerini reaction); 1007873-41-7P Role: SPN (Synthetic preparation), PREP (Preparation) (lithium bromide-promoted three-component synthesis of oxa-bridged tetracyclic tetrahydroisoquinoline derivs. (without concurrent Passerini reaction); 75-07-0 (Acetaldehyde); 104-53-0 (Benzenepropanal); 111-71-7 (Heptanal); 1664-62-6 (3-(2-Aminophenyl)-2-propenoic acid methyl ester); 6688-11-5 (Cyclooctanecarboxaldehyde); 85059-48-9 (DL-2-Isocyano-1-(morpholin-4-yl)-3-phenyl-1-propanone); 336105-88-5 (2-Isocyano-1-(4-morpholinyl)-2-phenylethanoen); 380374-16-3; 380374-17-4 (3-(6-Amino-1,3-benzodioxol-5-yl)-2-propenoic acid ethyl ester); 380374-20-9; 380374-21-0; 380374-35-6 (4-[2-Isocyano-3-(4-methoxyphenyl)-1-oxopropyl]morpholine); 1007873-30-4 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of (alkyl)tetrahydro(morpholinyl)-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylates via lithium bromide-promoted, stereoselective Ugi three-component reaction of aldehyde, (isocyano)(morpholinyl)alkanone, (aminophenyl)propenoate); 380374-23-2P; 380374-25-4P; 1007873-35-9P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of (alkyl)tetrahydro(morpholinyl)-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylates via lithium bromide-promoted, stereoselective Ugi three-component reaction of aldehyde, (isocyano)(morpholinyl)alkanone, (aminophenyl)propenoate); 7550-35-8 (Lithium bromide) Role: RGT (Reagent), RACT (Reactant or reagent) (prepn. of (alkyl)tetrahydro(morpholinyl)-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylates via lithium bromide-promoted, stereoselective Ugi three-component reaction of aldehyde, (isocyano)(morpholinyl)alkanone, (aminophenyl)propenoate); 380374-24-3P; 380374-27-6P; 380374-28-7P; 380374-29-8P; 380374-33-4P; 1007873-33-7P; 1007873-34-8P; 1007873-36-0P; 1007873-37-1P; 1007873-38-2P; 1007873-39-3P; 1007873-40-6P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of (alkyl)tetrahydro(morpholinyl)-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylates via lithium bromide-promoted, stereoselective Ugi three-component reaction of aldehyde, (isocyano)(morpholinyl)alkanone, (aminophenyl)propenoate); 1007873-42-8P; 1007873-44-0P; 1007873-45-1P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of (alkyl)tetrahydro(morpholinyl)benzo[f][1,7]naphthyridine-1-carboxylate via fragmentation of 2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylate precursor); 85059-38-7 (1-(2-Isocyano-1-oxo-3-phenylpropyl)piperidine) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of (alkyl)tetrahydro(piperidinyl)-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylates via lithium bromide-promoted, stereoselective Ugi three-component reaction of aldehyde, (isocyano)(piperidinyl)alkanone, (aminophenyl)propenoate); 1007873-31-5P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of (alkyl)tetrahydro(piperidinyl)-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylates via lithium bromide-promoted, stereoselective Ugi three-component reaction of aldehyde, (isocyano)(piperidinyl)alkanone, (aminophenyl)propenoate); 1007873-32-6P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of (alkyl)tetrahydro(piperidinyl)-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylates via lithium bromide-promoted, stereoselective Ugi three-component reaction of aldehyde, (isocyano)(piperidinyl)alkanone, (aminophenyl)propenoate); 1007873-43-9P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of (alkyl)tetrahydro(piperidinyl)benzo[f][1,7]naphthyridine-1-carboxylate via fragmentation of 2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylate precursor)
Laboratories:




 Record created 2010-11-25, last modified 2018-03-17


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