Expeditious Entry to Novel 2-Methylene-2,3-dihydrofuro[3,2-c]chromen-2-ones from 6-Chloro-4-hydroxychromen-2-one and Propargylic Alcohols

A catalytic system consisting of the ruthenium(II) complex [Ru(η3-2-C3H4Me)(CO)(dppf)][SbF6] (dppf = 1,1’-bis(diphenylphosphino)ferrocene) and trifluoroacetic acid has been used to promote the coupling of secondary propargylic alcohols with 6-chloro-4-hydroxychromen-2-one. The reactions afforded unusual 2-methylene-2,3-dihydrofuro[3,2-c]chromen-2-ones in good yields.


Results and Discussion
Initially, the coupling of the secondary propargylic alcohol 1-(4-methoxyphenyl)-2-propyn-1-ol (2a) with 6-chloro-4-hydroxychromen-2-one (3) was investigated under the same reaction conditions previously employed by us in the synthesis of furo[3,2-c]chromen-2-one derivatives starting from 4-hydroxychromen-2-one [21], that is, heating a THF solution of both reactants (equimolar mixture) at 75 °C in the presence of 50 mol% of trifluoroacetic acid and 5 mol% of the allyl-ruthenium(II) complex 1 (Scheme 2). Almost complete disappearance of the starting materials, accompanied by the selective formation of a single reaction product 4a, was observed by GC after 8 hours of heating. Appropriate chromatographic workup allowed the isolation of 4a as a crystalline yellow solid in 83% yield. NMR spectroscopic data obtained for 4a clearly revealed the selective formation of a 2-methylene-2,3-dihydrofuran unit, instead of the expected aromatic 2-methylfuran one (details are given in the Experimental), a fact that was unambiguously confirmed by means of a single-crystal X-ray diffraction study (an ORTEP view of the molecule is shown in Figure 3; selected bonding parameters are listed in Table 2). The bond distance C10-C11 (1.321(3) Å) showed the expected value for a C=C bond, while that observed for C10-C12 (1.523(3) Å) falls within the expected range for a C(sp 2 )-C(sp 3 ) single bond.  Table 2. Selected bond distances (Å) and angles (°) for compound 4a.
The presence of a 2-methylene-2,3-dihydrofuran moiety in the structure of these compounds was readily identified by the appearance of a high-field CH carbon resonance at 43-49 ppm (CHR unit) and a CH 2 signal at ca. 92 ppm, typical of a terminal olefinic =CH 2 unit, in their 13 C{ 1 H}-NMR spectra (DEPT experiments). Characteristic 1 H-NMR peaks for these units were also observed at 4.5-5.5 ppm (details can be found in the Experimental).

General
Solvents were dried by standard methods and distilled under nitrogen before use. The complex [Ru(η 3 -2-C 3 H 4 Me)(CO)(dppf)][SbF 6 ] (1) [36] and propargylic alcohols 2a-d [37] were prepared by following the methods reported in the literature. Flash chromatography was performed using Merck silica gel 60 (230-400 mesh). Melting points were determined in a Gallenkamp apparatus and are uncorrected. Infrared spectra were recorded on a Perkin-Elmer 1720-XFT spectrometer. NMR spectra were recorded on a Bruker DPX-300 instrument at 300 MHz ( 1 H) or 75.4 MHz ( 13 C). The chemical shift values (δ) are given in parts per million and are referred to the residual peak of the deuterated solvent used (CDCl 3 ). High-resolution mass spectra (HRMS) were provided by the Mass Spectrometry Service of the Instituto de Investigaciones Químicas (IIQ-CSIC, Seville). CCDC 831021 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

X-ray Crystal Structure Determination of Compound 4a
The most relevant crystal and refinement data are collected in Table 1. Data collection was performed on a Oxford Diffraction Xcalibur Nova single crystal diffractometer, using Cu-Kα radiation. Images were collected at a 65 mm fixed crystal-to-detector distance using the oscillation method, with 1° oscillation and a 5 s exposure time per image. Data collection strategy was calculated with the program CrysAlis Pro CCD [38]. Data reduction and cell refinement were performed with the program CrysAlis Pro RED [38]. An empirical absorption correction was applied using the SCALE3 ABSPACK algorithm as implemented in the program CrysAlis Pro RED [38]. The software package WinGX was used for space group determination, structure solution and refinement [39]. The structure was solved by direct methods using SIR92 [40]. Isotropic least-squares refinement on F 2 using SHELXL97 was performed [41]. During the final stages of the refinements, all the positional parameters and the anisotropic temperature factors of all the non-H atoms were refined. The coordinates of the H atoms were found from different Fourier maps and included in a refinement with isotropic parameters. )/3. Atomic scattering factors were taken from the International Tables for X-ray Crystallography [42].
The crystallographic plot was made with PLATON [43].

Conclusions
In summary, an efficient synthesis of unusual and remarkably stable 2-methylene-2,3dihydrofuro[3,2-c]chromen-2-one derivatives, by coupling of secondary propargylic alcohols with commercially available 6-chloro-4-hydroxychromen-2-one, has been developed with the aid of the catalytic system [Ru(η 3 -2-C 3 H 4 Me)(CO)(dppf)][SbF 6 ]/CF 3 CO 2 H. Apparently, the presence of the electron-withdrawing Cl substituent on the 4-hydroxychromen-2-one skeleton exerts a marked influence on the behavior of these species since, as previously described by us [21], the same reactions performed with its non-substituted counterpart leads to the selective formation of isomeric furo[3,2c]chromen-2-ones by aromatization of the five-membered ring. Overall, the results reported herein represent a new example of the utility of the allyl-ruthenium(II) complex 1 in synthetic organic chemistry [25].