A highly regioselective intermolecular cyclotrimerization of terminal alkynes has been developed based on the use of the cationic rhodium(I)/DTBM-Segphos complex. This method can be applied to a variety of terminal alkynes to provide 1,2,4-trisubstituted benzenes in high yield and with high regioselectivity. A chemo- and regioselective intermolecular crossed-cyclotrimerization of dialkyl acetylenedicarboxylates with a variety of terminal alkynes has also been developed based on the use of the cationic rhodium(I)/H8-BINAP complex, furnishing 3,6-disubstituted phthalates in high yields. It constitutes a highly efficient new method for intermolecular crossed-cyclotrimerization of two different monoynes in terms of catalytic activity, chemo- and regioselectivity, scope of substrates, and ease of operation. The versatility of this new crossed-alkyne cyclotrimerization procedure is demonstrated through its application to one-step synthesis of a [6]metacyclophane and [7]-[12]paracyclophanes from the corresponding terminal alpha,omega-diynes. Mechanistic studies have revealed that the chemo- and regioselectivity of this crossed-alkyne cyclotrimerization are determined by the preferential formation of a specific rhodium metallacycle derived from a terminal alkyne and a dialkyl acetylenedicarboxylate.

We have achieved the first catalytic enantioselective synthesis of planar-chiral metacyclophanes by means of cationic rhodium(I)/(R)-H8-BINAP complex-catalyzed alkyne cyclotrimerization. This reaction represents a versatile new method for the preparation of planar-chiral [7]−[10]metacyclophanes.

Ligularia stenocephala MATSUM. et KOIDZ. (Compositae) has long been used as a Chinese folk medicine in the treatment of edema and scrofula.1) The constituents of L. stenocephala have been previously investigated and shown to contain benzofuran derivatives. [1][2][3][4][5] Here, we report the isolation and structural elucidation of three new dimeric benzofuran derivatives, ligulacephalins A (1), B (2) and C (3), together with three known compounds from the roots of L. stenocephala. The known compounds were identified as 5,6-dimethoxy-2-isopropenylbenzofuran (4), 2) euparin (5) 6) and (R)-(Ϫ)-hydroxytremetone (6), 7) respectively, by comparison of their spectroscopic data with those previously described in the literature.Ligulacephalin A (1) was obtained as an amorphous powder. The molecular formula was determined to be C 26 H 28 O 6 by high-resolution (HR)-electron ionization (EI)-MS, indicating thirteen degrees of unsaturation. The UV absorption maxima at 206, 249sh, 255 and 295 nm indicated the presence of a benzofuran ring.8) The presence of 13 carbons and 14 hydrogens shown in the NMR spectra, and an intense ion peak at m/z 218 (M ϩ /2, 100%) in the EI-MS, suggested the symmetrical nature of 1. The 1 H-and 13 C-NMR data (vide Experimental) indicated that 1 possessed one methyl group, one methylene group, two methoxyl groups, one quaternary carbon and a benzofuran skeleton. Interpretation of the 1 Hdetected heteronuclear multiple-bond coherence (HMBC) and nuclear Overhauser effect correlation spectroscopy (NOESY) data led to the half-unit of the molecule (Fig. 1). Based on the molecular formula, C-10 must form a cyclobutane ring with C-10Ј or C-12Ј. The coupling pattern and the constants for the methylene protons [d 1.94 (2H, AAЈXXЈ type, H-12a, H-12Јb), 2.78 (2H, AAЈXXЈ type, H-12b, H12Јa); Coupling constants, J AX ϭ11.3 Hz, J AXЈ ϭ9.5 Hz, J AAЈ ϭ9.0 Hz, J XXЈ ϭ3.8 Hz] suggested a head-to-head dimeric structure.9,10) Thus the gross structure of ligulacephalin A was determined to be as shown in 1. The relative stereochemistry was determined as follows. In the long-range 1 H-1 H shift correlation spectroscopy ( 1 H-1 H COSY) spectrum, a Wtype coupling was observed between H 3 -11Ј and H-12Јa, indicating their anticoplanar orientation (Fig. 2) Kazuki TOYODA, Yasunori YAOITA, and Masao KIKUCHI* Tohoku Pharmaceutical University; 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan. Received July 6, 2005; accepted August 24, 2005 Three new dimeric benzofuran derivatives, ligulacephalins A (1), B (2) and C (3), were isolated from the roots of Ligularia stenocephala MATSUM. ET

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Cross‐cyclotrimerizations of ether‐linked α,ω‐diynes and dimethyl acetylenedicarboxylate in the presence of a catalytic amount of cationic rhodium(I)/H8‐BINAP complex give [7]–[21]polyether cyclophanes in good yield. [8]–[9]Ester cyclophanes were also synthesized from the corresponding α,ω‐diynes. The ratio of para‐, meta‐, and orthocyclophanes depends on the length and the structure of the α,ω‐diyne tether chain, whilst the effect of concentration on the yield of polyether cyclophanes appears to be small. X‐ray analysis revealed that a single crystal of [15]metacyclophane 4g was the chiral form and that of [5.5]metacyclophane 4k the racemic form, due to an absence of ring flip in the crystals. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)