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An α-regio-, diastereo-, and enantioselective [3 + 2] annulation reaction of Morita–Baylis–Hillman carbonates of isatins and activated alkenes with a bulky electron-withdrawing 1,2-benzoisothiazole 1,1-dioxide or 1,2,3-benzoxathiazine 2,2-dioxide motif is reported, furnishing an array of spirooxindoles (>19:1 dr, up to >99% ee) catalyzed by cinchona-derived tertiary amines. Density functional theory calculation studies have been conducted to elucidate the originality of the α-regioselective annulations.

The title compound is synthesized from L-tyrosine via Pd-catalyzed stereoselective oxazine formation and subsequent hydrogenation.

The compound is synthesized from a chiral 1,3-oxazine using Wittig reaction followed by a cyclization as key features over ten steps with an overall yield of 15.7%.

The convenient and effective protecting group 4-(dimethylamino)benzyl reported for the synthesis of the title compounds can be cleaved selectively by using TFA.

3-(2-Bromoacetyl)tropolone (1) reacted with several benzaldehydes 2a-e to afford 2-arylidene-3,8-dihydro-2H-cyclohepta[b]furan-3,8-diones 3a-e in very good yields.

3-(2-Bromoacetyl)tropolone (1) reacted with benzaldehydes 2a-g in the pressence of alkali at low temperature to give 2-aryl-3-hydroxy-4,9-dihydrocyclohepta[b]pyran-4,9-diones 3a-g in good yields.

2 When3-dihydro-1H-cyclohepta[b]pyrazine (3) was treated with acetyl chloride under the Friedel-Crafts conditions, its pyrazine ring opened to afford 2-[N'-acetyl-(2-aminoethyl)amino]tropone. Reactions with propionyl and butyryl chloride also gave similarly ring-opened products. On the other hand, aromatic benzoyl chlorides reacted with compound 3 to afford N-benzoyl-substituted 2,3-dihydro-1H-cyclohepta[b]pyrazines, in addition to ring-opened compounds.

3-Acetyltropolone (1) reacted with 2-hydroxybenzaldehyde (3a) in the presence of perchloric acid in ethyl orthoformate to afford 2-(3-tropolonyl)-1-benzopyrylium perchlorate (4a). The reactions with 2-hydroxy-5-methylbenzaldehyde (3b), 5-chloro-2-hydroxybenzaldehyde (3c), and 2-hydroxy-1-naphthalde-hyde (3d) gave respectively the corresponding products 4b-d. The reactions of 2-acetyl-7-methylamino-tropone (2) with 3a-d also gave the corresponding products 5a-d, respectively.

3-Acetyltropolone (1) reacted with 2-methoxybenzaldehyde (2a) in the presence of ethyl orthoformate and perchloric acid to afford 2-(2-methoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-dione (3a). The reactions with 3,4-dimethoxybenzaldehyde (2b), vanillin (2c), and piperonal (2d) gave respectively the corresponding products 3b-d. The reaction with benzaldehyde (2e) gave uncyclized 3-cinnamoyltropolone (4).

3-Isopropenyltropolones 1a-c were treated with bromine in carbon tetrachloride to give 3-methyl-8H-cyclohepta[b]furan-8-ones 2a-c and their corresponding 7-bromo-substituted compounds 3a-c, while reactions in acetic acid gave the bromo-substituted compounds 3a-c. On the other hand, bromination of 1a-c with N-bromosuccinimide afforded 7-bromo-3-(2-bromo-1-methylethenyl)tropolones 5a-c. The compound 2a was treated with bromine to give 2-bromo-3-methyl-8H-cyclohepta[b]furan-8-one (4). The tropolones 5a-c were heated in the presence of potassium carbonate to give the cyclized compounds 3a-c.

3-Acetyltropolone was brominated with phenyltrimethylammonium tribromide to afford 3-(2-bromoacetyl)-tropolone (2), whose reactions with thiourea, thioformamide, and ammonium dithiocarbamate gave respectively 3-(2-amino-4-thiazolyl)-, 3-(4-thiazolyl)-, and 3-(2-mercapto-4-thiazolyl)tropolone. In a similar manner, compound 2 was treated with six 1-substituted 2-thioureas and three thioamides to give the corresponding 3-(4-thiazolyl)tropolone derivatives.

3-Acetyltropolone (1) reacted with bromine, iodine, and nitric acid to afford respectively 3-acetyl-5,7-di-bromotropolone (2), 3-acetyl-7-iodotropolone (3), and 3-acetyl-5-nitro- (4) and 3-acetyl-5,7-dinitrotropolone (5). Azo-coupling reactions of 1 gave 3-acetyl-5-arylazotropolones 7a-f. The Schmidt reactions of 2 and 3 gave respectively 5,7-dibromo- (9) and 7-iodo-2-methyl-8H-cyclohept[d]oxazol-8-one (10), while 4 gave 3-acetamido-5-nitrotropolone (11). Compounds 2 and 4 reacted with hydroxylamine to give 3-methyl-8H-cyclohept[d]isoxazol-8-ones 12 and 13. The reactions of 2, 3, and 4 with hydrazine gave 3-methyl-1,8-dihydrocycloheptapyrazol-8-ones 15, 16, and 17.

3-Cinnamoyltropolone (1) reacted with bromine to afford 7-bromo- (2), 5,7-dibromo-3-cinnamoyltropolone (3), and 6,8-dibromo-4,9-dihydrocyclohepta[b]pyrane-4,9-dione (4) according to amount of the reagent. Iodination and nitration of 1 gave respectively 7-iodo- (5) and 5-nitro-3-cinnamoyltropolone (6). Azo-coupling reactions gave 5-arylazo-3-cinnamoyltropolones 7a-f. Compounds 1, 2, 3 and 5 reacted with hydroxylamine to give 3-styryl-8H-cyclohept[d]isoxazol-8-ones 10-13, while 6 and 7a gave 5-nitro-3-styryl-8H-cyclohept[d]-isoxazol-8-one oxime (14) and 2-cinnamoyl-7-methoxy-4-phenylazotropone (15), respectively. The reactions of 1,3, and 5 with phenylhydrazine gave 3-styryl-1,8-dihydrocycloheptapyrazol-8-ones 16-19.

3-Acetamidotropolone (1a) reacted with bromine and fuming nitric acid to afford respectively 3-acetamido-7-bromo- (1b) and -5,7-dibromotropolone (1c) and 3-acetamido-5-nitrotropolone (1d). Azo-coupling reaction of 1a gave 3-acetamido-5-(4-methylphenylazo)tropolone (1f). Bromination of 1d and 1f gave 7-bromo-substituted compounds 1e and 1g, respectively. The compounds 1b-g were hydrolyzed to afford 3-aminotropolones 4b-g, which reacted with triethyl orthoformate to give the corresponding 8H-cyclohept[d]oxazol-8-ones 5b-g. Heating of 3-acetamidotropolones 1a-d with polyphosphoric acid gave 2-methyl-8H-cyclohept[d]oxazol-8-ones 6a-d.