rac-(1S,2R)-Diethyl 6-hydroxy-1-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-benzo[f]chromen-2-yl]phosphonate

In the title compound, C24H25O7P, the δ-valerolactonyl ring exists in a distorted screw-boat conformation with the diethoxyphosphoryl substituent occupying an axial position. The latter adopts an almost syn-periplanar conformation around the P—C bond. The molecules form centrosymmetric dimers connected by O—H⋯O hydrogen bonds.


Comment
The 4-aryl-3,4-dihydrocoumarin (neoflavonoid) moiety is found in several natural compounds which show a wide range of biological activities. Among them, the anti-inflammatory, anti-oxidative and anti-aging properties are best recognized (Zhang et al., 2006). A number of neoflavonoids isolated from various plant sources revealed cytotoxic and chemopreventive activity against cancer (Bailly et al., 2003). Morever, some 4-aryl-3,4-dihydrocoumarin derivatives exhibit estrogenic activity (Roelens et al., 2005). The most common method for the synthesis of 4-aryl-3,4-dihydrocoumarins involves Michael type addition of electron-rich hydroxyarenes to cinnamic acids or their derivatives (Aoki et al., 2005;Li et al., 2005;Rizzi et al., 2006). Unfortunately this method is limited to the reactions of cinnamic acid bearing electron-donationg groups on the aromatic ring. Recently we developed a novel synthesis of the dihydrocoumarins based on CF 3 SO 3 H promoted Friedel Crafts reaction of electron-rich hydroxyarenes (Krawczyk et al., 2007a) with the (E)-3-aryl-2-(diethoxyphosphoryl)acrylic acids. The title compound (I) is a key product of that synthesis.
The title compound (I) represents a novel dihydrocoumarine analog in which the δ-valerolactone ring bears the P-C bond. A related compound (II) in which the electron-donating para-methoxy substituent was replaced by the electron-withdrawing Br atom has been published by us recently (Krawczyk et al., 2007b). A search of the Cambridge Structural Database (Version 5.29;Allen, 2002) showed that crystal structures of the related compounds have not been reported so far.
A view of (I), with atom numbering scheme is shown in Fig. 1. The δ-valerolactone and naphtalene moieties are almost coplanar with one another. The former ring adopts conformation close to a 4 S 3 screw-boat (Boeyens, 1978), with O1, C1, C3, C4 and C9 almost coplanar (the average r.m.s. deviation from the mean plane is 0.09 Å) and C2 situated at the flap.
The former group adopts an almost synperiplanar conformation along the P-C2 bond (Fig. 2). This arrangement is supplementary materials sup-2 A superposition of structures (I) and (II), as presented in Fig. 3, clearly shows similarity of the neoflavonoid fragments. The major difference is position of the O5-C22-C23 diethoxy group. In (I) this group points away from the naphtalene fragment while in (II) it is almost paralel and involved in the C-H-π(arom) interaction. The latter stabilizes a virtual eclipsed conformation along the axial P-C bond as was found in (II).
In the crystal molecules form centrosymmetric dimers connected by strong, practically linear hydrogen bonds linking phosphoryl and hydroxyl groups of both monomers. In terms of Etter's graph-set terminology (Etter, 1990;Bernstein, et al., 1995) this system can be described as R 2 2 (20).

Experimental
The solution 1,3-dihydroxynaphtalene in CH 2 Cl 2 , trifluoromethanesulfonic acid and (E)-2-diethoxyphosphoryl-3-(4methoxyphenyl)acrylic acid were added and a resulting mixture was left at room temperature for 1 day. After the acrylic acid was completely reacted, saturated NaHCO 3 solution was added. The organic layer was separated, washed with water and dried over MgSO 4 . Evaporation of the solvent under reduced preasure gave a crude product which was purified by column chromatography and recrystalized from diethyl ether.

Refinement
H atoms were located on difference Fourier maps and refined as riding on their carrier O or C atoms with U iso (H) = 1.2U eq (O or C). The methyl groups were allowed to rotate about their local threefold axis. AFIX 84, AFIX 14, AFIX 24, AFIX 44 and AFIX 138 procedures as in SHELXTL (Sheldrick, 2008) were applied. Fig. 1. The molecule of the title compound (I). Displacement elipsoids are drawn at the 50% probability level.