The direct synthesis of the title amino acid derivatives from carboxylic esters and nitrones can be achieved in fair to good yields when lithium or magnesium ester enolates were treated with nitrones in THF at -78 °C or in Et2O at -20 to 0 °C, respectively. The products from the reaction of t-butyl acetate with 3,4-dihydroisoquinoline N-oxide or 5,5-dimethylpyrroline 1-oxide were transformed into (1,2,3,4-tetrahydroisoquinolin-1-ylidene)acetate or (pyrrolidin-2-ylidene)acetate derivatives in the presence of triphenylphosphine, carbon tetrachloride, and triethylamine in refluxing dichloromethane.

2-(1-Hydroxyalkyl)-1,4-naphthoquinones are found to react with pyrrolidino enamines in toluene to give 1H-naphtho[2,3-c]pyran-5,10-diones in good yields via a tandem conjugate addition-cyclization sequence, followed by an elimination of pyrrolidine. 2-Hydroxymethyl-1,4-naphthoquinone and morpholino enamines undergo a similar sequence, without loss of morpholine, to yield 3-morpholino-3,4-dihydro-1H-naphtho[2,3-c]pyran-5,10-diones. The 3-morpholino group of these products can be replaced with a hydro, a hydroxy, or a methoxy group. Imines also react with 2-(1-hydroxyalkyl)-1,4-naphthoquinones to give the corresponding 1H-naphtho[2,3-c]pyran-5,10-diones, including a natural product (pentalongin). The utility of these reactions is demonstrated in the synthesis of pyranonaphthoquinone antibiotics, viz. (±)-eleutherin and (±)-isoeleutherin.

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A new and simple method for the preparation of 3,3-disubstituted isoindolin-1-ones from a-substituted 2-bromostyrenes is described. Construction of the isoindolin-1-one skeleton was accomplished by treating a-substituted secondary 2-vinylbenzamides, easily obtainable from the reaction of a-substituted 2-lithiostyrenes with isocyanates, with iodine to afford 3-substituted 3-iodomethylisoindolin-1-ones.A number of synthetic methods for 3-substituted isoindolin-1-ones have been reported, 1 mainly on account of their biological interest. 2 For example, the alkylation of 2-substituted 3-lithioisoindolin-1-ones, first reported by Couture et al., 1b is one of the most efficient methods for preparing this class of compounds. However, there have been few reports on the synthesis of 3,3-disubstituted derivatives in literature. 3 In this paper we wish to demonstrate that the intramolecular iodoamination 4 of asubstituted secondary 2-vinylbenzamides provides a simple and convenient method for the synthesis of 3,3-disubstituted isoindolin-1-one derivatives. 5 Our synthesis of 3,3-disubstituted isoindolin-1-one derivatives was conducted as outlined in Scheme 1. Thus, the bromine-lithium exchange between readily available asubstituted 2-bromostyrenes 1 and butyllithium in diethyl ether at 0 °C for one hour generated the corresponding asubstituted 2-lithiostyrenes. Almost complete generation of 1-(2-lithiophenyl)-1-phenylethene from 1a was confirmed by obtaining 1,1-diphenylethene almost quantitatively after quenching with aqueous ammonium chloride. Then, these lithium products were allowed to react with isocyanates to give the a-substituted secondary 2-vinylbenzamides 2 in the yields summarized in Table 1. It indicates that aliphatic isocyanates (entries 3 and 4) gave poorer results than aromatic isocyanates (entries 1, 2, 5, and 6). The moderate yields of 2 may be ascribed to the liability of isocyanates to oligomerization.The regioselective intramolecular iodoamination of these amides 2 proceeded smoothly on treatment with iodine in the presence of sodium hydrogen carbonate in acetonitrile at 0 °C to give the 3-iodomethylisoindolin-1-one derivatives 3 in fair to good yields. Reduction of the iodo moiety of 3 with tributyltin hydride smoothly proceeded in benzene at room temperature to afford the 3-methylisoindolin-1-one derivatives 4 in fair to good yields. These results are also summarized in Table 1.We attempted the nucleophilic substitution reactions of 3a with sodium thiolates; however, this resulted in the formation of intractable mixtures of products.In conclusion, we have shown that 3,3-disubstituted isoindolin-1-ones can be synthesized in two steps from readily available a-substituted 2-bromostyrenes and under milder reaction conditions. This method may find some value in synthesis because of its simplicity.The melting points were determined on a Laboratory Devices MEL-TEMP II melting-point apparatus and are uncorrected. The IR spectra were recorded on a Shimadzu FTIR-8300 spectrometer. The 1 H NMR spectra were deter...

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