Benzopyranone derivatives

In an alternative strategy functionalized phenols, such as iodophenol, were involved in palladium-catalyzed carbonylation of alkynes or allenes, producing coumarin or chromone derivatives (Scheme 23) [130-133]. After oxidative addition of the iodoarene to the Pd(0) catalyst the order of insertion of either CO or the unsaturated substrate mainly depends on the nature of the substrate. In fact, Alper et al. reported that CO insertion occurs prior to allene insertion leading to methylene- or vinyl-benzopyranone derivatives [130]. On the contrary, insertion of alkynes precedes insertion of CO, affording couma-rine derivatives, as reported by Larock et al. According to the authors, this unusual selectivity can be explained by the inability of the acyl palladium species to further react with the alkyne, hence the decarbonylation step occurs preferentially [131-133]. 

It is interesting to note that addition of NaH to Zn reducing agent in toluene facilitates the reductive coupling reaction of benzopyranone derivatives. Under these conditions, side products (e.g. reduction of C-I bond) can be suppressed. This reaction has been used for the synthesis of bisbenzopyran-4-ol [17]. 

Many 1,2,3,5-benzenetetrol derivatives are used mediciaaHy. For example, khellin [82-02-0] (65), which is a naturally occurring benzopyranone, is used as a coronary vasodilator and bronchodilator (233). Derivatives of khellin are effective local anesthetics and antiarrythmics (234). Similarly, amine derivatives (68) that are prepared from khellinone oxime (66) exhibit hypnotic, sedative, anticonvulsant, antiinflammatory, cardiac analeptic, diuretic, and antiulcerous activity (235) (see Analgesics, antipyretics, and antiinflammatory agents). 

In addition to the preceding chemotypes, thiazoles, quinolin-2-ones and cycloalkanothieno-pyrimido-thiazoles [79], azolepyrimidines derivatives, trisubstituted pyrimidines, benzo[fc]thiophenecarboxamides and benzofu-rancarboxamides [80-83], and substituted benzopyranones have also been claimed in different patents as PI3K inhibitors [1]. 

Bromobenzyl alcohol and its derivatives were converted to phthalides by the palladium catalysed insertion of carbon monoxide and intramolecular quenching of the formed acylpalladium complex. 2-Hydroxymethyl-1-bromonaphthaline, for example, gave the tricyclic product in excellent yield (3.34.). An interesting feature of the process is the use of molybdenum hexacarbonyl as carbon monoxide source. The reaction was also extended to isoindolones, phthalimides and dihydro-benzopyranones 42... 

A similar carbonyl addition with benzaldehyde derivatives having an ortho-allylic ether led to a benzopyranone when treated with potassium hexamethyldisilazide. ° These reactions are not successful when the alkene contains electron-withdrawing groups, such as halo or carbonyl groups. A free-radical initiator is required, usually peroxides or UV light. The mechanism is illustrated for aldehydes but is similar for the other compounds ... 

Other miscellaneous systems [2c] include phenoxazones, quinolinones, phtalo-cyanines, benzopyranones, rhodanines, Rose Bengal peroxybenzoate, crystal violet/ benzofuranone derivatives, dimethyl aminostyryl benzothiazolinium iodides, etc. 

The n.m.r. spectra of some benzopyranones and the mass spectra of simple alkyl-chromones and their deuteriated derivatives have been investi-gated. p, pj ... 

Since its discovery, Wessely-Moser rearrangement has been widely used in the structural elucidation of flavanones, chromones, xanthones, and their derivatives. Its popularity should be largely attributed to the fact that differentiation between a 5,7,8-arranged benzopyranone and its 5,6,7-isomer is often difficult, and sometimes impossible, by the classical techniques such as NMR studies (even with shift reagents). ... 

Shimojima, Y., and H. Hayashi lH-2-Benzopyran-l-one derivatives, Microbial Products with Pharmacological Activity. Relationships between Structure and Activity in 6-[[l S-(3S,4-Dihydro-8-hydroxy-l-0X0-1 H-2-benzopyranon-3-yl-3-methylbu-tyl]amino]-4S,5S-dihydroxy-6-oxo-3S-ammoniohexanate. J. Med. Chem. 26, 1370 (1983). 

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