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Diels–Alder reactions of five-membered heterocycles containing one heteroatom with an N-arylmaleimide were studied. Cycloaddition of 2,5-dimethylfuran (4) with 2-(4-methylphenyl)maleimide (3) in toluene at 60 °C gave bicyclic adduct 5. Cycloadditions of 3 with 2,5-dimethylthiophene (11) and 1,2,5-trimethylpyrrole (14) were also studied. Interestingly, the bicyclic compound 5 cleanly rearranged, with loss of water, when treated with p-toluenesulfonic acid in toluene at 80 °C to give 4,7-dimethyl-2-p-tolylisoindoline-1,3-dione (6).

We have previously attempted to prepare 5-(4-morpholinyl)-2-aminothiophene ( 3 ) by reducing 5-(4-morpholinyl)-2-nitrothiophene ( 2 ), to prepare a precursor for the preparation of thienyloxazolidinones as potential linezolid-like antibiotics. This strategy failed, but allowed us to define an interesting reductive aromatization reaction. We have now succeeded in producing thienyloxazolidinones using an alternative strategy, initiating from 5-(4-morpholinyl)thiophene-2-carboxaldehyde ( 8 ). This Letter describes the synthesis of thienyloxazolidinone 14 , which is a key intermediate for the preparation of new oxazolidinone antibiotics with a thiophene core.

The Cadogan–Sundberg indole synthesis produces two major products from the treatment of 2-nitrostilbenes with triethyl phosphite, which are the 2-arylindoles and the corresponding 2-aryl-N-ethoxyindoles. We were interested in determining the origin of the oxygen atom in the 2-aryl-N-ethoxyindoles. In this study, we verify that this oxygen atom originates from the nitro group and not from the triethyl phosphite.

2-Pyridones are well-known ambident nucleophiles which are capable of reacting with electrophiles through either the nitrogen or oxygen atom to form N-alkyl-2-pyridones or 2-alkoxypyridines, respectively. It has been shown that the ratio of these products can be affected by a number of factors including the nature of the electrophile, the base used for deprotonation, and the solvent. We have now discovered a relationship between the ratio of N- and O-alkylation products and the nature of substituents on the pyridone ring when the Mitsunobu reaction is used to alkylate 2-pyridones.

Two new syntheses of the phytoalexin methyl 1-methoxyindole-3-carboxylate (1) were developed that employ the same key intermediate. Methyl 2-(2-nitrophenyl)acrylate (2) was directly converted into phytoalexin 1 using modified Cadogan–Sundberg indole synthesis conditions with trimethyl phosphite. Acrylate 2 also underwent reductive cyclization with stannous chloride to give methyl 1-hydroxyindole-3-carboxylate (3), which was methylated to produce phytoalexin 1.

An efficient synthesis of new imidazo[1,2-b]pyridazine derivatives was effected by treating 3,6-dichloropyridazine with various 2-hydroxyethylamines following by imidazole ring formation under Swern oxidative conditions. Some mechanistic aspects of the cyclization step are discussed.

A concise method for the preparation of α-amino pentafluoroethyl ketone salts from amino acids is described. These intermediates are useful for the preparation of peptidyl pentafluoroethyl ketones.

Opening of the epoxide of (E)-4-phenyl-2-buten-1-ol with trimethylaluminum gave two phenonium ion-mediated products, whose ratio was dependent on reaction conditions.

A new method for the synthesis of peptidyl α-keto esters is described, which is particularly useful for the construction of proteinase inhibitors with a lysine side chain.

The title carbocyclic amine 15 , prepared in high yield from isoxazolidine 8 using efficient oxidation-epimerization-reduction sequence, is an inhibitor of mung bean αmannosidase II and a potent inhibitor of jack bean α-mannosidase.

The oxidation of α-hydroxy esters, including peptidyl α-hydroxy esters, with the Dess-Martin periodinane reagent is a useful and general method for the preparation of α-keto esters.