Isochromane-3-one

Acetanilides, benzoyl-colour couplers in colour photography, 1, 372 Acetanilides, pivaloyl-colour couplers in colour photography, 1, 372 Acetazolamide — see l,3,4-Thiadiazole-2-sulfonamide, 5-acetamido-Acetic acid, acetamidocyano-ethyl ester, 1, 307 Acetic acid, 2-acylphenyl-isochroman-3-one synthesis from, 3, 858 Acetic acid, 3-benzo[6]thiophenyl-biological activity, 4, 912 Acetic acid, l,2-benzoxazol-3-yl-electrophilic substitution, 6, 48... 

An investigation established a relationship between the intensity of the [M - C02] ion in the spectra of substituted isochroman-3-ones (29) and the yield of the corresponding benzocyclobutene (29a), obtained from flash vacuum pyrolysis of (29 equation 5) (77JOC2989). 

The three isomers which are discussed in this section are isochroman-l-one or 3,4-dihydroisocoumarin (617), isochroman-3-one (618) and isochroman-4-one (619). None of them enjoy an extensive chemistry although a small number of natural products contain an isochromanone nucleus. 

Methoxymethylbenzyl chloride is readily converted into the nitrile, which on treatment with acid yields isochroman-3-one. Alkaline hydrolysis does not bring about ring closure but simply gives the substituted phenylacetic acid (54JCS2819). 

A convenient synthesis of isochroman-3-one is based on the reaction of phenylacetic acids with formalin and concentrated hydrochloric acid (760S(55)45>. An indication of the value of the isochromanone as a synthetic intermediate is given in this procedure. 

A similar approach has been used to synthesize isochroman-3-ones (80JA4193). o-Bromomethylbenzyl alcohol oxidatively adds to the zerovalent complex and carbonylation and reductive elimination of the catalyst follow. The catalyst is kept active by the presence of base which absorbs the hydrogen bromide formed in the reaction. 

The Baeyer-Villiger oxidation of indan-2-one gives isochroman-3-one in good yield (49JCS1720). 

Imidate salts hydrolysis, 118-144 syn and anti, 120 isomerization, 142 B-lactam, 142 Iminium salts, 211-221 Imino-ethers, 147 lodolactonization, 169 Ionic state of tetrahedral intermediates, 65, 105-106, 119 Ionophore A-23187, 13 Isochromane-3-one, 70 Isocyanate, 300 Isonitrile, 296... 

A More Complex Benzocyclobutane To Isochroman-3-one Rearrangement (c.f. Problem 138)... 

Isochromen-3-yl trifluoromethanesulfonate 162, formed from isochroman-3-one, can undergo a palladium-catalyzed cross-coupling reaction with the boronate 163 to afford ( )-3-(l-ethoxybuta-l,3-dienyl)-177-isochromene in moderate yield (Scheme 52) <2005T3429>. 

The reaction between ClTi(Of-Pr)3 and 7-PrMgBr generates a low-valent titanium reagent, diisopropoxy(q2-prope-ne)titanium, which mediates the cyclization of the alkynic carbonates 1158 to isochroman-3-ones 1160 via the intermediate 1159 (Scheme 287) <1995TL6075, 1996JA2208>. 

A Lewis-acid-promoted cyclization of ethene tricarboxylate derivatived aromatic compounds 1162 provides a route to isochroman-3-ones 1163 via a Friedel-Crafts intramolecular Michael addition protocol. The substrate must possess two ///f to-positioncd electron donating groups in order for the reaction to proceed (Equation 452) <20040BC3134>. 

Benzocyclobutenones 1164 undergo heterolytic C( 1)—G(4) bond fission and reaction with aldehydes to provide a route to isochroman-3-ones 1165 (Equation 453, Table 55) <1997TL8985>. 

Synthesis of the isochroman-3-one 1167 can be achieved by a nickel-catalyzed intermolecular cyclization of the ortho-haloester 1166 and benzaldehyde, with the ( )-isomer predominating in the product (Equation 454) <2004CEJ2991>. 

Rhodium-catalyzed cyclization and carbonylation of 2-ethynylbenzylalcohols 1168 under water-gas shift reaction conditions leads to isochroman-3-ones (Equation 455) <1998TL5061>. 

The carbonylation of (2-ethynylphenyl)methanol is catalyzed by Pd(OAc)2 in the presence of 2-(diphenylphos-phino)pyridine (2-PyPPh2) to provide 4-methyleneisochroman-3-one, isolated in poor yield due to its instability (Equation 456) <2002TL753>. The synthesis of isochroman-3-one can be achieved by a palladium and Hi-mediated carbonylation of l,2-bis(hydroxymethyl)benzene <1998BCJ723>. 

Treatment of pentasubstituted benzene 1169 with an excess of paraformaldehyde in the presence of ZnCl2 under acidic conditions successfully installs a chloromethyl group ortho- to the acetic acid substituent, furnishing a mixture of 1170 and the cyclized isochroman-3-one 1171. As these acidic conditions are not themselves enough to totally finish the cyclization, basic hydrolysis is conducted to complete the cyclization to the isochroman-3-one 1171, a key intermediate during a synthesis of mimosamycin (Scheme 288) <2000JOC635>. 

Treatment of substituted phthalans 1172 with lithium metal in the presence of catalytic quantities of naphthalene leads to reductive cleavage of the arylmethyl carbon-oxygen bond to form a stable dilithium compound 1173, which upon trapping with carbon dioxide furnishes isochroman-3-ones 1174 (Scheme 289) <1996JOC4913>. 

Vinylnorcaradiene derivatives 1175 undergo a photochemical reaction resulting in the regioselective cleavage of one of the cyclopropyl a-bonds and the formation of isochroman-3-ones (Equation 457) <1997CC1973>. 

Carbon monoxide reacts with the palladacycle 1176 to form the intermediate 1177, which undergoes reductive elimination to afford isochroman-3-one (Scheme 290) <20050M1119>. 

Fukumoto et al have taken advantage of the propensity for inward rotation of an acyl group to prepare the isochroman-3-one (36), an intermediate in their synthesis of geneserine, a constituent of the calabar bean. The conversion of the benzocyclobutene (37) to (36) proceeds via ring opening to the o-quinodimethane (38) followed by cyclization and a 3,3-sigmatropic rearrangement. 

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