Carbonylation phthalide

Condensation of an appropriately substituted phenylacetic acid with phthalic anhydride in the presence of sodium acetate leads to aldol-like reaction of the methylene group on the acid with the carbonyl on the anhydride. Dehydration followed by decarboxylation of the intermediate affords the methylenephthal-ides (12). Treatment of the phthalides with base affords directly the indandiones, probably via an intermediate formally derived from the keto-acid anion (13). The first agent of this class to be introduced was phenindandione (14) this was followed by anisindandione (1S) and chlorindandione (16). ... 

Condensation of benzotriazole with 2-carboxybenzaldehyde gives 3-(benzotriazol-l-yl)phthalide 795 (Scheme 127). The anion derived from phthalide 795 adds to the ft-carbon atom of a,( -unsaturated carbonyl compounds E to produce anion 796 that by intramolecular nucleophilic attack on the phthalide carbonyl group is converted to anion 797. Spontaneous expulsion of benzotriazole from molecules 797 followed by aromatization leads to 1,4-dihydroxy-naphthalenes 798 <1997SC3951>. 

The first examples of a homogeneous reduction of this type were reported in 1971. Cobalt carbonyl was found to reduce anhydrides such as acetic anhydride, succinic anhydride and propionic anhydride to mixtures of aldehydes and acids. However, scant experimental details were recorded [94]. In 1975, Lyons reported that [Ru(PPh3)3Cl2] catalyzes the reduction of succinic and phthalic anhydrides to the lactones y-bulyrolaclone and phthalide, respectively [95], The proposed reaction sequence for phthalic anhydride is shown in Scheme 15.15. Conversion of phthalic anhydride was complete in 21 h at 90 °C, but yielded an equal mixture of the lactone, phthalide (TON = 100 TOF 5) and o-phthalic acid, which is presumably formed by hydrolysis of the anhydride by water during lactoniza-tion. Neither acid or lactone were further hydrogenated to any extent using this catalyst system, under these conditions. 

Hohe Ausbeuten an primaren aliphatischen Aminen liefert auch die reduktive Spaltung von N-Alkyl-phthalimiden mit Natrium-boranat in 2-Propanol/Wasser (6 1). Unter den Reaktionsbedingungen entsteht durch Reduktion einer Carbonyl-Gruppe und nachfol-gende Hydrolyse das entsprechendeN-Alkyl-2-hydroxymethyl-benzamid, das durch Erhitzen mit Essigsaure in Phthalid und das primare Amin gespalten wird4. 

In cyclic anhydrides and imides, one carbonyl group is usually easily reduced thus, phthalic anhydride with H2/Ni gives phthalide (287), and phthalimides with Zn/HCl yield phthalamides (288). Indoxyl and its 0- and 5-analogues can be reduced (Zn-HOAc) to indole, etc. 

Vinylbenzoic acids on cyclization yield either isochroman-l-ones or phthalides or a mixture of both types. The direction of ring closure is influenced by both steric and electronic factors (62AC(R)1070). The presence of an a-substituent in the vinylbenzoic acid (621 R = Ph) leads to phthalides, whereas only isochromanones result when no such substituent is present (621 R = H Scheme 238). Ring closure presumably involves attack by the carbonyl group at the centre of lowest electron density. Thus, 2-(l-methylethenyl)benzoic acid yields the phthalide, but 2-(2-methylpropenyl)benzoic acid gives the isochroman-l-one on halolac-tonization. 

Ikariya and co-workers reported an efficient palladium-catalyzed carbonylation of aryl halides in sc C02 (eq. 2.10) (Kayaki et al., 1999). 2-Iodobenzyl alcohol was converted to the phthalide in the presence of PdCl2L2 [L = PMe3, PPh3, MeCN, P(OEt)3, P(OPh)3, PPh(OMe)2, PPh2(OMe)] with higher rates in sc C02 than in toluene. 

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>. 

Thallationr-carbonylaiion of aromatics. ort/io-Thallation of benzoic acids, ben-zylic and (3-phenethyl alcohols, and benzamides followed by Pd(ID-catalyzed carbonyl-ation provides a route to aromatic carbonyl compounds such as phthalides, anhydrides, and imides. 

Two groups report the addition of metalated benzamides to aldehyde carbonyls. The methods differ in the metal. Lithiated diethylamides must be transmetalated with MgBr2 before addition to the aldehyde, but p-aminoamides react similarly as the lithium derivative. Following addition, the hydroxyamide is hydrolyzed to afford phthalides in moderate overall yield (Scheme 11). 

The catalytic carbonylation of halides can also be used to synthesize phthalides (equation 46). The reaction will proceed bodi in the presence of palladium and cobal7 catalysts. 

Michael addition of phthalide anions with a,P-unsaturated carbonyl compounds, followed by cyclisation provide substituted naphthols. 

A, as a y-lactone. The fact that the carbonyl absorption of methoxy-phthalides occurs near 5.68 /a and hence homolycorine must be the... 

Phthalides have an extremely high oxidative potential (2.86 V) (03GC512). Selective fluorination also takes place in the case of carbonyl-containing heterocyclic compounds. Thus mono- and difluoro derivatives of 4-(metho-xyphenyl)acetone and ethyl 4-(methoxyphenyl)acetate (87TL2359, 98JFC(87)215) and fluoroindanes (90TL3137) are produced by anodic fluorination of hydrocarbon substrates in the... 

Palladium-catalyzed carbonylation of iodo alcohol (158) affords a 22% yield of dioxocinone (147), together with a 12% yield of phthalide (Scheme 43) the latter is the sole product obtained upon attempted formation of the ten-membered ring analogue <89JMOCi45>. 

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