Catalysis phthalides

Buffer catalysis is observed in the intramolecular tranesterification of ethyl 2-hydroxymethyl benzoate to phthalide [equation (24)] (Fife and Benjamin, 1973). There is general base catalysis by... 

A highly efficient synthesis of l-alkylidene-13-dihydroisobenzofurans and 3-alkylidene isobenzofuran-l(3//)-ones (phthalides) through Pd-Cu-catalysis using acetylenic carbinols as synthons was reported <99SL456>. 

Since aikenes and aikynes can be prepared via Heck and Sonogashira reactions, respectively, tandem processes are also possible for lactone synthesis [71-77]. Appropriately, o-iodobenzoic acids can generate both phthalide and isocoumarin derivatives under Pd catalysis, with a Cul co-catalyst favoring the former and... 

Substituted benzaldehydes can be self-coupled oxidatively to give C(3)-substituted phthalides (146), using a rhodium(III)/aniline dual catalysis. The cascade ortho-C-M- (g) activation/insertion/annulation sequence can also be used in a heterocoupling sense with a second aldehyde. The dual catalysis allows plenty of scope for generating an enantios-elective version. 

Let us look at another example 2,2 -tolancarboxylic acid (1-4) in ethanol is converted to 3-(2-carboxybenzilidene) phthalide (1-5). The rate of the reaction is 10" faster than with the corresponding 2-tolancarboxylic or 2,4 -tolancarboxylic acid. Consequently, one carboxyl group acts as a general acid catalyst (see Chapter 4) by a mechanism known as complementary bU functional catalysis. 

Attempts have been made to detect bifunctional catalysis in the reactions of acetals with two carboxyl groups but the results indicate that if this occurs the rate enhancement over that found with just intramolecular general-acid catalysis is relatively small [15,16]. Thus the pH-rate profile for the conversion of the acid 13 into the corresponding phthalide is bell-shaped but at the maximum the rate constant is only three times greater than that for the hydrolysis of the acid 14 [15]. A larger effect is found in the reactions of the disalicyl-acetals 15 in dioxan-water to yield the corresponding dioxanone 16... 

Rh(III)-amine dual catalysis was developed by Seayad and coworkers in 2013 (Scheme 6.4) [12]. Both aryl- and alkyl-substituted phthalides were isolated in medium to high yields in the presence of [RhCp Cl2]2, AgBF, Ag2COg, and 4-trifluoromethylaniline. 

Formylarylketones are readily isomerized in dimethyl sulfoxide (DMSO) to 3-substituted phthalides by photolysis or by a Cannizarro-Tishchenko-type nucleophilic catalysis by NaCN. ... 

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