Shuhei Fukamachi

SYNTHESIS OF 2-BENZOTHIOPHENE-1(3H)-THIONE AND ISOTHIOCHROMENE-1-THIONE DERIVATIVES BY IODINE-MEDIATED CYCLIZATION OF LITHIUM 2-(VINYL)DITHIOBENZOATE DERIVATIVES

Successive treatment of α-substituted 2-bromostyrenes with butyllithium and carbon disulfide generates lithium 2-(vinyl)dithiobenzoates, which are then allowed to react with iodine to give 3-substituted 3-iodomethyl-2-benzothiophene-1(3H)-thiones and/or 4-substituted isothiochromene-1-thiones in one-pot. Some of the former products can be transformed into the corresponding latter products on treatment with sodium hydrogencarbonate in refluxing acetonitrile.

NEW, FACILE SYNTHESIS OF 3,3-DISUBSTITUTED PHTHALIDES BASED ON THE REACTION OF α-SUBSTITUTED 2-LITHIOSTYRENES WITH CARBON DIOXIDE

A new method to prepare 3,3-disubstituted phthalides [isobenzofuran-1(3H)-ones] from α-substituted 2-bromostyrenes has been developed. The reaction of α-substituted 2-lithiostyrenes, generated in situ by bromine-lithium exchange between α-substituted 2-bromostyrenes and butyllithium, with carbon dioxide gave the corresponding lithium 2-vinylbenzoates, which upon treatment with concentrated hydrochloric acid afforded the desired products in one pot.

SYNTHESIS OF 3-SUBSTITUTED BENZO[b]THIOPHENES VIA THE REACTION OF α-SUBSTITUTED 2-LITHIO-β-METHOXYSTYRENES WITH SULFUR

3-Substitued benzo[b]thiophenes were synthesized in reasonable overall yields from α-substituted 2-bromo-β-methoxystyrenes. Thus, the bromine-lithium exchange between these bromostyrenes with butyllithium in diethyl ether at 0 °C followed by reaction with sulfur afforded the corresponding α-substituted β-methoxy-2-sulfanylstyrenes. These were then treated with an equimolar amount of concentrated hydriodic acid in acetonitrile at room temperature to give the desired products.

A facile synthesis of 1,1-disubstituted isoindoline derivatives by intramolecular iodoamination of 2-vinylbenzylamine derivatives

The intramolecular iodoamination of N-(2-vinylbenzyl)acetamide derivatives, derived from α-substituted 2-vinylbenzonitriles in two steps, afforded the corresponding 2-acetyl-1 -iodomethylisoindoline derivatives, which were transformed into the 1-methyl or 1-sulfenylmethyl derivatives by tributyltin hydride reduction or substitution by sodium thiolates, respectively, in reasonable yields.

CONVENIENT SYNTHESIS OF 1,3-DIHYDROISOBENZOFURANS BY HYDRIODIC ACID-CATALYZED CYCLIZATION OF 2-VINYLBENZYL ALCOHOLS

A new and short process has been developed for the preparation of 1,1,3-tri- and 1,1,3,3-tetra-substituted 1,3-dihydroisobenzofurans (phthalanes) from α-substituted 2-bromostyrenes. The method involves addition of α-substituted 2-lithiostyrenes, generated by the bromine-lithium exchange between α-substituted 2-bromostyrenes and butyllithium, to aliphatic aldehydes or ketones, followed by hydriodic acid catalyzed cyclization of the resulting 2-vinylbenzyl alcohols.

One-pot synthesis of 4-substituted isothiochroman-1-thiones from α-substituted 2-bromostyrenes and carbon disulfide

A facile method for the preparation of isothiochroman-1-thiones has been developed. Thus, treatment of α-substituted 2-lithiostyrenes, generated in situ from bromine-lithium exchange between the respective 2-bromostyrenes and butyllithium, with carbon disulfide, followed by workup with saturated aqueous ammonium chloride, affords 4-substituted isothiochroman-1-thiones in reasonable yields.

SYNTHESIS OF 1,4-DIHYDRO-2H-3,1-BENZOXAZIN-2-ONES BY HYDRIODIC ACID MEDIATED CYCLIZATION OF t-BUTYL 2-VINYLPHENYLCARBAMATES

A two-step facile synthesis of 4,4-disubstituted 1,4-dihydro-2H-3,1-benzoxazin-2-ones starting from α-substituted 2-aminostyrenes is described. The method involves the hydriodic acid mediated cyclization of t-butyl 2-vinylphenylcarbamate derivatives, which could be easily prepared by N-t-butoxycarbonylation of α-substituted 2-aminostyrene derivatives, under mild conditions.

Synthesis of 1H-isoindol-3-amine derivatives by iodine-mediated cyclization of 2-vinylbenzamidine derivatives

It has been found that the reaction of 2-vinylbenzamidine derivatives, prepared by reacting 2-vinylbenzonitriles with lithium cyclic secondary amides, with iodine in the presence of sodium hydrogen carbonate in acetonitrile resulted in the formation of the corresponding l-iodomethyl-1H-isoindole-3-amine derivatives in reasonable overall yields based on the starting 2-vinylbenzonitriles. We have also found that transformation of these 1-iodomethyl derivatives into 1-sulfenylmethyl derivatives could be achieved in good yields on treatment with various sodium thiolates.

Synthesis of isochromans by hydriodic acid or iodine mediated cyclization reactions of 1-(2-vinylphenyl)propan-2-ols

Treatment of 1-(2-vinylphenyl)propan-2-ols, which can be easily prepared from 2-bromostyrenes and epoxides, with hydriodic acid in acetonitrile yields the corresponding isochromans (1H-3,4-dihydro-2-benzopyrans). When the above alcohols are treated with iodine in acetonitrile in the presence of sodium hydrogencarbonate, the corresponding 1-iodomethylisochromans are obtained, which can be easily converted into the corresponding 1-alkyl(or aryl)sulfanylmethylisochromans on treatment with sodium thiolates in DMF.

Synthesis of 1-(1-arylsulfanylalkyl)indoles and 2,2-bis[1-(1-arylsulfanylalkyl)indol-3-yl]propanes by acid-catalyzed reactions of indoles with aryl vinyl sulfides

We report a facile synthesis of 1-(1-arylsulfanylalkyl)indoles and 2,2-bis[1-(1-arylsulfanylalkyl)indol-3-yl]propanes under mild conditions. Thus, treatment of 3-substituted indoles with aryl vinyl sulfides in dichloromethane at room temperature in the presence of a catalytic amount of (±)-camphor-10-sulfonic acid yields the former indole derivatives in moderate to fair yields. 3-Nonsubstituted indoles can be transformed into the latter indole derivatives in satisfactory yields on treatment with excess aryl vinyl sulfides in the presence of a catalytic amount of the acid under similar conditions.