Alkylidene phthalides

Mediated by a palladium(n)-copper(n) catalytic system benzoic and naphthoic acids react with styrene to yield a mixture of isocoumarins 784 and alkylidene phthalides 785 (Scheme 214, Table 32) <1998JOC5211>. 

DBU-catalyzed lactonization of t>-alkynyl benzoic acids proceeds with high regioselectivities (>95 5) to produce alkylidene phthalides in good to excellent yields (Scheme 94) <2007TL933>. 

Benzofuran 213 has been patented for use as a UV absorber in cosmetics and as a UV stabilizer in plastics <1997USP5665334>. A wide range of 3-substituted phthalides, for example, 214, and 3-alkylidene phthalides 215, are used in dermatological formulations to protect dibenzoylmethane compounds in the compositions from UV radiation <2003FRP2827509>. 

Alkylidene phthalides are produced from 5-exo-dig cyclization of o-alkynylbenzoic acids. However, concomitant generation of isocoumarins via 6-endo-dig cyclization is normally problematic [63]. 

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>. 

A highly efficient synthesis of l-alkylidene-l,3-dihydrobenzo[f]furans from t>-hydroxymethyl iodoarenes and propargyl alcohols uses a bimetallic Pd/Cu-catalyzed Sonogashira coupling/cyclization reaction (Equation 132) <1999SL456>. Pd/l,4-bis(diphenylphosphino)butane (DPPB)-catalyzed reaction of t>-allylphenols under a CO atmosphere leads to carbonylative cyclization to form benzannulated lactones <2006ASC1855>. A similar carbonylative cyclization leads to the stereoselective formation of 3-alkenyl phthalides <2006T4563>. 

Phthalic anhydrides can be easily converted to phthalimides, simple phthalides, alkylidene and benzylidine phthalides, and anthraquinones. A few interesting examples are depicted below. 

Replacing the Cul with ZnCl2 affords primarily isocoumarins [30]. The direct reaction of o-halobenzoic acids with copper acetylides also affords phthalides [22-24]. The reaction of (Z)-3-halopropenoic acid and terminal alkynes in the presence of a palladium catalyst and catalytic amounts of Cul provides a convenient synthesis of alkylidene butenolides (Eq. 8) [31,32]. 

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