Benzopyranones, reactions

In the realm of natural product synthesis, Kepler and Rehder utilized the K-R reaction to synthesize ( )-calanolide A (56), a potent non-nucleosidal human irmnunodeficiency virus (HIV-1) specific reverse transcriptase inhibitor. Propiophenone 57 was allowed to react with acetic anhydride in the presence of sodium acetate to afford benzopyranone 58 in 56% yield subsequent deacetylation of 58 gave 59. Flavone 59 was then transformed to ( ) calanolide A (56) over several steps. 

She and co-workers took advantage of the acyl anion equivalent formed from the addition of an NHC to an aldehyde to catalyze the formation of benzopyranones via an intramolecular S 2 displacement (Scheme 50) [167], Various aromatic aldehydes provide alkylation products in moderate yields when the leaving group is either tosylate or iodide. No reaction was observed when phenyl or methyl was placed alpha to the leaving group. 

The unstable dibenz[c,/][l,2]oxazepines (312 R = CN, Cl) have been isolated as the major products of the UV irradiation of 9-cyano- and 9-chloro-acridine 10-oxides (310) in benzene (c/. the analogous Af-imide to 1,2-diazepine conversion on p. 598). Although none of the oxaziridine tautomer (311) was detectable by UV spectroscopy, the subsequent deoxygenation of (312) to acridine suggests the existence of a thermal equilibrium between (311) and (312) (79T1273). These dibenzo compounds (312) are the only fully unsaturated oxazepines yet isolated but the 2,3-benzoxazepin-l-one system (314) has recently been prepared by the reaction of benzonitrile oxide with the benzopyranone (313) (80JCS(Pl)846). 

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... 

The 2,3-benzoxazepin-l-one system (436) is prepared by the reaction of benzonitrile oxide with the benzopyranone (435) (80JCS(P1)846). The tetrahydro-3,2-benzothiazepine 3,3-dioxide (438) was prepared from (437) by intramolecular sulfonamidomethylation (76CC470). 

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 ... 

An alternative ring expansion process involving the benzopyranone (77) and the 1,3-dipole benzonitrile oxide, generated in situ from A-a-chlorobenzylidenehydroxylamine, affords access in low yield (8.4%) to the functionalized 2,3-benzoxazepin-l-one system (78) (m.p. 155-156°C). An analogous reaction is demonstrated by A-benzylideneaniline A-oxide to give (79) (m.p. 266-267°C) in 16% yield (Scheme 9) <80JCS(Pi)846>. 

Reaction with Cyclic Enones. Conjugate addition of azide ion to cyclic enones in water using sodium azide in the presence of Lewis base resulted in the formation of 8-azido carbonyl compounds (eq 55). The Schmidt reaction of benzopyranones with sodium azide led to pyrano[3,2-b]azepines in reasonable yields (eq 56). 

Besides the synthesis of various triazoles, the synthetic potential of the copper flow system was further demonstrated by the catalytic decarboxylation of the propargyhc add 11 (Scheme 4, Reaction 2) and the C—O coupling in the synthesis of benzopyranone 14 (Scheme 4, Reaction 3) (2010SL2009). 

The ortho-arylation reaction of phenolates with aryldiazonium sulfides as radical precursors represents an efficient process for the synthesis of benzopyranones and related compounds (Equation 13.4). The intermediately formed SrnI products are readily transformed in situ to the corresponding benzopyranones under mild acidic reaction conditions [15]. 

Wessely-Moser rearrangement refers to the rearrangement of benzopyran-4-ones possessing a 5-hydroxyl group, such as the demethylation product of 5,7,8-methoxyflavone 1, to yield scutellarein 2, its isomeric product. Acidic conditions are most commonly used for such transformation however, several examples of base-catalyzed reactions have also been reported. The reversibility of the rearrangement largely depends on the substituent pattern of the benzopyranone. 

Upon careful examination of reaction parameters, Tanaka and coworkers successfully developed a highly enantioselective lactone synthesis by reaction with both aldehydes and activated ketones as the coupling partners for the synthesis of spirocyclic benzopyranones. Cationic Rh catalysts were again found to be the most efficient. Importantly, homodimerization of the parent 2-aIkynylbenzaldehydes was not observed under the optimized conditions [92]. 

This year has seen the publication of the first convenient synthesis of crotonophenones, which are open chain forms of benzopyranones (chromanones). Previous attempts at their synthesis via Friedel-Crafts or simple aldol reactions gave poor yields. However, it has now been shown that the dianion of n-hydroxyacetophenones will react with aldehydes, and dehydration of the products constitutes a simple synthesis of crotonophenones and also of 2-methyl chromanones. 

Cyclocondensations of ethyl [ CJcyanoacetate to produce other product types are exemplified (Figure 7.441 by the reaction with benzopyranone nitrile 186 to give in... 

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]. 

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