3- Allyl-4-quinolones

In their work on antimalarial compounds, Saltzer et al.4 also effected similar rearrangements. In every instance, the products were assumed to be the corresponding 3-allyl-4-quinolones (see Table II). 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

The scope of this approach was widened by the observation of excellent enantioselectivities in intermolecular [2+ 2]-photocycloaddition reactions with various alkenes [62,71]. In the presence of an excess amount of alkene, 4-me thoxy-2-quinolone (57) was converted with high chemo- and regioselectivity to the exo and endo cyclobutanes 59 and 60. With 4-penten-1-ol (58a), allyl acetate (58b), methyl acrylate (58c), and vinyl acetate (58d), the exo diastereomers 59a-d were formed with high simple diastereoselectivity and in high yields (80-89%), Under optimized irradiation conditions (2.4 eq. of host 44 or ent-44, — 60°C), high enantiomeric excesses were achieved in all instances, as depicted in Scheme 22. These enantiomeric excesses are unprecedented for an intermolecular photochemical reaction. 

In the host-guest complex of template 60 with substrate 61, the two enantio-faces of quinolone 61 are distinctly discriminated. As one of the enantiofaces of 61 is blocked by the benzotriazole moiety of 60, photochemical attack to the substrate is expected to occur from the open face. Indeed, in the presence of 60 and its enantiomer (ent-60), highly enantioselective intramolecular [2 + 2] photocycloaddition of allyl quinolonyl ether 62 [134] and intermolecular [2 + 2] photocycloaddition of quinolone 61 to alkenes 63 [135] were reported to occur in solution (Scheme 23). The intermolecular photocyeloaddition of 63 to 61, as well as the intramolecular photocyeloaddition of 62 proceeded with excellent enantioselectivities (81-98% ee) and in high yields (61-89%). 

Rearrangements of allyloxyquinolines were carried out as early as 1924.14 2-Allyloxyquinoline was prepared by reacting 2-chloroquino-line with sodium allyloxide in allyl alcohol. The ether was rearranged by heating it to 325-329°. l-Allyl-2-quinolone was isolated as the product. Even attempted distillation of the starting ether at atmospheric pressure resulted in the formation of the quinolone. The l-allyl-2-... 

Allyl and crotyl ethers were prepared from 3-propyl-4-quinolones by two different approaches. Displacement of 4-chloro-3-propyl-quinoline by the sodium salt of the two alcohols gave the ethers (1) as clean products, whereas reacting 3-propyl-4-hydroxyquinoline with allyl bromide in the presence of sodium ethoxide afforded not only the allyl ether but also the 1-allylquinolone (2). The products were well-characterized by their ultraviolet spectra and infrared bands. Rearrangement of the ethers at 200° without solvent gave quantitative yields of the corresponding l-allyl-3-propyl-4-quinolones (2). 

Further support for this observation was secured from a study of the rearrangement of the two ethers 3-allyl-4-methallyloxyquinoline and 4-allyloxy-3-methallylquinoline. The quinolone product obtained in quantitative yields in both cases was found by infrared spectral analysis to be a 1 1 mixture of the two possible structures (3 and 4). 

Mitscher and co-workers (30) have explored alternative methods of synthesizing 3-prenyl-2-quinolones (Scheme 2) whereby the formation of by-products characteristic of the prenylmalonate route is avoided by blocking the 3-position. Thus, allylation of the 3-bromo-4-hydroxy-Af-methyl-2-quinolone yielded ketone 19 which, with zinc and acid, was converted into the 3-prenyl-2-quinolone (20). The ketone 22, obtained from ester 21, was transformed into the 2-quinolone (20) by heating with copper acetate in hexamethylphosphorus triamide. 

Furoquinoline alkaloids specifically labeled with 14C in the furan ring were required for biosynthetic studies (see Section VII of this chapter), and since existing routes produced low yields, Grundon and co-workers (195, 196) developed a more efficient synthesis from 4-methoxy-3-prenyl-2-quinolones 244-246. These compounds had previously been prepared from aromatic amines and substituted malonates, but direct allylation is more suitable for the preparation of labeled compounds, employing, for example, [14C]-3,3-dimethylallyl bromide. It was found that reaction of... 

The reaction of isatoic anhydrides with the anions derived from active-methylene compounds has led to the isolation of a considerable number and variety of quinolones.There have been two reports of the preparation of cycloalkano-pyridines, e.g. (137), by thermolysis of cycloalkanone oxime O-allyl ethers, e.g. (135) an intermediate nitrone (136) is formed (Scheme 56). 

The reaction of haplophyllidine (11) or its hydration product, perforine (12), with concentrated sulphuric acid results in dehydration, loss of methanol, and cyclization the structure (13) of the product was established by spectroscopy and by conversion, with methyl iodide, into the corresponding N-methyl-4-quinolone. The reaction of the Haplophyllum alkaloid haplatine (14) with methyl iodide also results in formation of an N-methyl-quinolone ( 15), and in this case the methylation of the allylic hydroxy-group gives a second product (16). Reductive cleavage of haplatine furnishes the 3-ethyl-2-quinolones (17) and (18). ... 

Intramolecular or intermolecular Heck-type reactions were also used in the synthesis of poly-substituted quinoline compounds. Palladium-catalyzed reaction between vinyl or aryl halides and ortAo-allyl-substituted-A -tosyl-anilides produces dihydroquinolines in an intermolecular fashion, where reaction of acrylates intramolecularly affords 4-quinolones. ° ° ... 

The group of Nakagawa reported the synthesis of quinoline 71 from N-allyl o-aminostyrenes 69 by using an RCM approach. Attempted deprotection of the dihydroquinolines 70 resulted in quinolone 71 (Scheme 20). Only one example was described, in quantitative yield (01TL8029). 

They are also useful in the kinetic resolution of 2,3-dihydro-4-quinolones by enantioselective allylic allylation. " ... 

Scheme 3.14 KR of 2,3-dihydro-2-substituted 4-quinolones through allylic alkylation.

N-allyl/N-vinyl anilines were characterized by a rearrangement of the ahphatic moiety. The aromatic system had not been touched during the course of the process (Winterfeldt quinolone synthesis [15c]). The rearrangement of a NH allyl vinyl amine failed [15dj. 

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