Naphthopyran Synthesis

J. Herscovici, S. Delatre, and K. Antonakis, Enantiospecific naphthopyran synthesis by intramolecular Diels-Alder cyclisation of 4-keto 2,3-unsaturated C-glycosides, Tetrahedron Leu. 32 1183 (1991). 

In later reports, Herscovici, eta/.,119 demonstrated the applicability of this technology to more complex allylic ethers. The example shown in Scheme 2.7.3 was utilized in an enantiospeciflc naphthopyran synthesis. 

Routes to 2//-[l]benzopyrans have been reviewed <75AHC(18)159, 77HC(31)11, 84CHEC-I(3)757, 96CHEC-II(5)351> and in many cases these methods are readily adaptable to naphthopyran synthesis. However, the specific interest here lies with naphthopyrans containing a gem diaryl imit, a substitution pattern that imposes restrictions on the synthetic approach. 

Naphtho[2,l -h]pyran-1 -one, 2,3-dihydro-dehydrogenation, 3, 724 halogenation, 3, 731 Naphthopyranones synthesis, 3, 805 Naphthopyran-2-ones, dihydrosynthesis, 3, 802 Naphtho[l, 2-h]pyran-2-ones synthesis, 3, 802 Naphtho[2,1 -h]pyran-3-ones synthesis, 3, 803, 856 Naphtho[2,1 -c]pyran-4-ones synthesis, 3, 831 Naphtho[2,3-c]pyran-l-ones synthesis, 3, 831 Naphthopyrans H NMR, 3, 580 IR spectra, 3, 594 synthesis, 3, 743, 748, 750, 763 UV spectra, 3, 598 Naphthopyrans, dihydrosynthesis, 3, 778, 783 Naphtho[l,2-h]pyran-4-thione, styryl-properties, 3, 708... 

A facile synthesis of substituted 2-hydroxy-3-dimethylaminopropenoates has been reported. These undergo addition with cyclic 1,3-diketones and (hetero)aromatic hydroxyl compounds to afford either 3-hydroxytetrahydro-277-Tbenzopyran-2-ones, benzo- and naphthopyran-2-ones, and azolo- and azinopyran-2-ones <1998T9799>. 

Unfortunately the pyridine-catalyzed condensation is largely unsuccessful with unsaturated ketones. Furthermore, there are few examples of the use of monohydric penhols in this synthesis. 1-Naphthol affords the naphthopyran (81) with citral, though in poor yield, and 2-naphthol gives (82). The latter example is of interest since it provides a further illustration of the regiospecificity arising from resonance stabilization. 

A bioxantracene (-)-ES-242-4 (46) was isolated from the culture broth of Verticillium sp. in 1992 as one of eight antagonists for the 7V-methy 1-D-aspartate (NMDA) receptor (7<5). These novel natural products are reported to inhibit the PH]thienyl cyclohexylpiperidine binding to rat crude synaptic membranes, and therefore, are of potential therapeutic interest for die treatment of neurodegenerative diseases. (-)-ES-242-4 (46) is structurally remarkable having an axially chiral binaphthalene core that is adorned with two pyrans of the same absolute chirality. Our interest in the construction of densely functionalized naphthopyran ring systems, via tandem Michael-Dieckmann reactions, promoted us to attempt the first stereocontrolled total synthesis of (-)-ES-242-4 (46) (19). 

When the annellated heteroaromatic group is a five-member ring (43, 44), the properties are best described as intermediate between a naphtho and benzopyran. The standard method of synthesis for diaryl naphthopyrans (acid-catalyzed condensation between a diaryl propargyl alcohol and a naphthol, Scheme 8) is reported not to work for heteroaromatic fused phenols. This is true especially in cases where the heteroaromatic phenol contains a (basic) nitrogen. Alternatively, these pyrans can be prepared by the method of Casiraghi69 outlined in Scheme 16. 

The following three preparations, adapted from the literature, demonstrate the primary methods of synthesis of benzo and naphthopyrans. 

The short and convenient synthesis of novel naphthopyranoquinolines from naphthopyran chloroaldehydes via the Doebner-Miller synthesis was developed in the laboratory of J.K. Ray. The chloroaldehydes were treated with 2.5 equivalents of a substituted aniline in ethanol in the presence of 2N HCI to afford enaminoimine hydrochlorides in good yield. These hydrochloride salts were exposed to heat at a temperature slightly above their melting point, resulting in ring-closure and elimination of one equivalent of arylamine hydrochloride. 

Xu, Y.-C., Kohiman, D. T., Liang, S. X., Erikkson, C. Stereoselective, Oxidative C-C Bond Coupling of Naphthopyran Induced by DDQ Stereocontrolled Total Synthesis of Deoxyfrenolicin. Org. Lett. 1999,1,1599-1602. 

Sami, I., Kar, G., Ray, J. K. Synthesis of polycyclic oxacoumarins, potential antitumor agents and a short and convenient synthesis of naphthopyranoquinolines from naphthopyran chloroaldehydes. Tetrahedron 992, 48, 5199-5208. 

The angular isomers, 2 and 3, have received much attention since they display good photochromic properties in solution under ambient conditions. Further structural diversity has been achieved by the fusion of aromatic and heterocyclic moieties onto 2Ff-[l]benzopyran and the isomeric naphthopyrans. This review discusses the consequences of the reversible opening of the pyran ring in such compounds under the influence of UV-irradiation and draws together the information reported in the scientific and patent literature concerning the synthesis and photochromic properties of these molecules. Particular attention is paid to the... 

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