Rhodium-Catalyzed Linear Codimerization and Cycloaddition of Ketenes with Alkynes

A novel rhodium-catalyzed linear codimerization of alkyl phenyl ketenes with internal alkynes to dienones and a novel synthesis of furans by an unusual cycloaddition of diaryl ketenes with internal alkynes have been developed. These reactions proceed smoothly with the same rhodium catalyst, RhCl(PPh3)3, and are highly dependent on the structure and reactivity of the starting ketenes.


Introduction
Ketenes are very important intermediates in the field of organic synthesis [1][2][3], and much attention has been focused on the ketene-metal complexes [4]. In general, ketenes coordinate to transition-metal complexes in two ways: 1) coordination through a C=C bond in ketenes [5], and 2) coordination OPEN ACCESS through a C=O bond in ketenes [6][7][8][9][10]. If these coordination modes can be controlled through the selection of ketenes in transition-metal catalysis, completely different methods for the construction of novel organic molecules could be developed according to the structure and reactivity of ketenes using the same transition-metal catalyst.
We have previously developed a ruthenium-catalyzed synthesis of pyranopyrandiones by the ringopening carbonylation of cyclopropenones [11] and a novel synthesis of 2-pyranones by the ruthenium-or rhodium catalyzed ring-opening dimerization of cyclobutenones [12], as well as a rhodium-catalyzed synthesis of 2-substituted phenols from cyclobutenones and alkenes via cleavage of a carbon-carbon bond [13]. We propose that (η 4 -bisketene)-and (η 4 -vinylketene)metal complexes are important key intermediates in these reactions; however, there are still few examples of transitionmetal complex-catalyzed transformations of ketenes themselves [14][15][16][17][18][19][20]. Thus, we focused our attention on the development of novel reactions of ketenes with unsaturated compounds in the presence of ruthenium or rhodium catalysts, and recently developed rhodium-catalyzed decarbonylative coupling reactions of diphenyl ketene with 2-norbornenes and electron-deficient alkenes [21]. Then, the reactions of ketenes with alkynes were investigated in the presence of several transition-metal catalysts. After many trials, we developed the novel RhCl(PPh 3 ) 3 -catalyzed linear codimerization of alkyl phenyl ketenes with internal alkynes and a novel synthesis of furans by the unusual RhCl(PPh 3 ) 3 -catalyzed cycloaddition of diaryl ketenes with internal alkynes. In these reactions, the catalyst is the same but the products are completely different, depending on the structure and reactivity of the starting ketenes.
In sharp contrast, treatment of diaryl ketenes 1d and e instead of alkyl phenyl ketenes 1a-c with internal alkynes 2 in the presence of the same RhCl(PPh 3 ) 3 catalyst (5 mol %) in mesitylene at 120 ºC for 12 h under an argon atmosphere gave unusual cycloadducts, the furans 4, instead of dienones 3, in good to high yields (Scheme 2). The structure of furan 4a was confirmed by 13 C Inadequate NMR measurement (see Experimental, Figure 2).
The catalytic activities of several transition-metal complexes were also examined in the reaction of diphenyl ketene (1d) with 3-hexyne (2a), and the results are summarized in Table 3. Among the catalysts examined, only RhCl(PPh 3 ) 3 showed catalytic activity (4a, 74%). Other rhodium, ruthenium, iridium and palladium complexes were totally ineffective in the present reaction. 6-Dodecyne (2b), as well as 4-octyne (2c) and 5-decyne (2d), reacted with 1d to give the corresponding furans 4b-d in moderate yields (Entries 2-4 in Table 4). As for ketenes, di(4-chlorophenyl) ketene (1e) also reacted with 2a to give the corresponding furan 4e in an isolated yield of 51% (Entry 5).  While the reaction mechanism is not yet clear, the possible mechanisms are illustrated in Schemes 3 and 4. Scheme 3 shows a possible mechanism of the reaction of alkyl phenyl ketenes 1a-c with internal alkynes 2 to give dienones 3. We now believe that the initial step is the coordination of alkyl phenyl ketenes 1 to an active rhodium center through a C=C bond in ketenes. Oxidative cyclization of alkyl phenyl ketenes 1a-c with alkynes 2 would give rhodacyclopentenone intermediates I [5].
Stereoselective β-hydrogen elimination, followed by reductive elimination, would give the corresponding dienones 3 stereoselectively. In addition, we now consider that a catalytically active species is a Rh(I) bearing a chloro ligand, and RhCl 3 . 3H 2 O would be reduced to a Rh(I)-Cl species by crystal water to show some catalytic activity (Entry 4 in Table 1).

Scheme 3.
A possible mechanism of linear codimerization of alkyl phenyl ketenes 1a-c with internal alkynes 2 to give dienones 3.

Scheme 4.
A possible mechanism of the synthesis of furans 4 by unusual cycloaddition of diaryl ketenes 1d and e with internal alkynes 2.
On the other hand, a possible mechanism for the reaction of diaryl ketenes 1d and e with internal alkynes 2 to furans 4 is shown in Scheme 4. In the synthesis of furans 4, the reaction starts from the coordination of diaryl ketenes to an active rhodium center through a C=O bond in ketenes (not through a C=C bond in ketenes). Oxidative cyclization of diaryl ketenes 1d, and e with alkynes 2 gives an oxametallacycle intermediate II [22][23][24][25]. β-Hydrogen elimination and insertion of an allenyl group in an intermediate III into a Rh-H bond, followed by reductive elimination/isomerization, would give the desired furans 4.

General
GLC analyses were carried out on a Shimadzu GC-18A gas chromatograph equipped with a glass column (2.8 mm i.d. × 3 m) packed with Silicone OV-17 (2% on Chromosorb W(AW-DMCS), 60-80 mesh). Recycling preparative HPLC was performed with an LC-918 (Japan Analytical Industry Co. Ltd.) equipped with JAIGEL-1H and 2H columns (GPC) using CHCl 3 as an eluent. 1 H-NMR spectra were recorded at 300 or 400 MHz, and 13 C-NMR spectra were recorded at 75 or 100 MHz. Samples were analyzed in CDCl 3 , and the chemical shift values are expressed relative to Me 4 Si as an internal standard. IR spectra were obtained on a Nicolet Impact 410 spectrometer. Elemental analyses were performed at the Microanalytical Center of Kyoto University.

General procedure for the rhodium-catalyzed reaction of ketenes with alkynes to give dienones and furans
A mixture of ketene 1 (1.0 mmol), alkyne 2 (3.0 mmol), RhCl(PPh 3 ) 3 (0.050 mmol), and mesitylene (1.0 mL) was placed in a two-necked 20-mL Pyrex flask equipped with a magnetic stirring bar and a reflux condenser under a flow of argon. The reaction was carried out at 120 ºC for 12 h with stirring. After the reaction mixture was cooled, the products were analyzed by GLC and isolated by Kugelrohr distillation followed by recycling preparative HPLC. of olefinic CH at δ 6.15 ppm gave a 6.7% NOE of the phenyl group at δ 7.26-7.28 ppm, while irradiation of CH 2 in ethyl group at δ 2.24 ppm showed 5.2% NOE with CH 3 in the other ethyl group at δ 1.03 ppm. The stereochemistry of 3a was therefore assigned to 2Z and 5E (Figure 1). The same method was used to determine the stereochemistry of 3b-d.

Conclusions
In conclusion, we have developed a novel rhodium-catalyzed cross-coupling reaction of ketenes with alkynes. The different coordination modes of ketenes to rhodium, which highly depend on the structure and reactivity of the starting ketenes, realized the selective formation of totally different products, dienones and furans in the presence of the same rhodium catalyst, RhCl(PPh 3 ) 3 . Both reactions proceed via characteristic rhodacyclic intermediates.