Aldehyde Addition to 1,3-Butadiyne-Derived Zirconacyclocumulenes

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Organometallics 2010, 29, 3012–3018 DOI: 10.1021/om100287d

Aldehyde Addition to 1,3-Butadiyne-Derived Zirconacyclocumulenes: Stereoselective Synthesis of cis-[3]Cumulenols Xiaoping Fu, Yuanhong Liu,* and Yuxue Li* State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, People’s Republic of China Received April 9, 2010

The direct addition of aldehydes to zirconacyclocumulenes generated through the coupling reactions of benzynezirconocenes with 1,3-butadiynes is achieved cleanly under controlled reaction conditions, which provids a highly stereoselective method for the synthesis of tetra-substituted [3]cumulenols. DFT calculations suggest that there is an equilibrium between seven-membered zirconacyclocumulene (3) and the less stable but more reactive five-membered R-alkynylzirconaindene (2) in the process. The aldehyde reacts with the five-membered zirconaindene intermediate through a cyclic SE20 pathway to afford cumulenol products after hydrolysis.

Introduction Zirconacycles, which are easily prepared by reductive coupling of unsaturated compounds such as alkynes, alkenes, nitriles, aldehydes, or ketones on a low-valent zirconocene equivalent, have attracted a lot of attention due to their versatile utility in organometallic and organic synthesis.1 For several years, our group has been interested in the development of new synthetic strategies based on zirconocene coupling of *Corresponding authors. E-mail: [email protected]. (1) For reviews, see: (a) , Q.; Lu, J.; HuWang, C.; Wang, C.; Xi, Z. Tetrahedron 2007, 63, 6614. (b) Titanium and Zirconium in Organic Synthesis, Marek, I., Ed.; Wiley-VCH: Weinheim, Germany, 2002. (c) Negishi, E.; Takahashi, T. In Organometallic Complexes of Zirconium and Hafnium, Science of Synthesis (Houben-Weyl Methods of Molecular Transformations); Imamoto, T., Ed.; Georg Thieme Verlag: Germany, 2003; pp 681-848. (d) Takahashi, T.; Xi, Z.; Hara, R. Trends Organomet. Chem. 1997, 2, 117. (e) Rosenthal, U.; Burlakov, V. V.; Arndt, P.; Baumann, W.; Spannenberg, A. Organometallics 2005, 24, 456. (f) Xi, Z.; Li, Z. Top. Organomet. Chem. 2004, 8, 27. (g) Buchwald, S. L. Science 1993, 261. (h) Kotora, M.; Xi, Z.; Takahashi, T. J. Synth. Org. Chem. Jpn. 1997, 55, 958. (i) Negishi, E.; Takahashi, T. Bull. Chem. Soc. Jpn. 1998, 71, 755. (j) Takahashi, T.; Xi, Z.; Kotora, M. Pure Appl. Chem. 1998, 2, 515. (k) Takahashi, T.; Kotora, M.; Hara, R.; Xi, Z. Bull. Chem. Soc. Jpn. 1999, 72, 2591. (2) (a) Fu, X.; Chen, J.; Li, G.; Liu, Y. Angew. Chem., Int. Ed. 2009, 48, 5500. (b) Chen, J.; Li, Y.; Gao, H.; Liu, Y. Organometallics 2008, 27, 5619. (c) Liu, Y.; Gao, H. Org. Lett. 2006, 8, 309. (d) Liu, Y.; Gao, H.; Zhou, S. Angew. Chem., Int. Ed. 2006, 45, 4163. For titanation of conjugated 1,3butadiynes and their coupling reactions with aldehydes, see: (e) Chen, J.; Liu, Y. Tetrahedron Lett. 2008, 49, 6655. For titanium-mediated trisubstituted cis-[3]cumulenols formation, see: (f) Chen, J.; Liu, Y. Organometallics 2010, 29, 505. (3) For reviews, see: (a) Rosenthal, U.; Burlakov, V. V.; Arndt, P.; Baumann, W.; Spannenberg, A. Organometallics 2005, 24, 456, and references therein. (b) Rosenthal, U.; Burlakov, V. V.; Arndt, P.; Baumann, W.; Spannenberg, A. Organometallics 2003, 22, 884. (c) Rosenthal, U. Angew. Chem. 2003, 115, 1838. ; Angew. Chem., Int. Ed. 2003, 42, 1794. (d) Rosenthal, U. Angew. Chem. 2004, 116, 3972. ; Angew. Chem., Int. Ed. 2004, 43, 3882. (e) Rosenthal, U.; Arndt, P.; Baumann, W.; Burlakov, V. V.; Spannenberg, A. J. Organomet. Chem. 2003, 670, 84. (f) Rosenthal, U. In Modern Acetylene Chemistry II-Chemistry, Biology, and Material Science; Diederich, F., Stang, P. J., Tykwinski, R. R., Eds.; Wiley-VCH: Weinheim, Germany, 2004; Chapter 4, p 139. (g) Rosenthal, U.; Pellny, P.; Kirchbauer, F. G.; Burlakov, V. V. Acc. Chem. Res. 2000, 33, 119. pubs.acs.org/Organometallics

Published on Web 06/04/2010

1,3-butadiynes.2 The chemistry of 1,3-butadiynes R(CtC)2R and polyynes R(CtC)nR with group 4 metallocenes3-5 has been extensively studied by Rosenthal et al.3 using the metallocene sources Cp2M(L)(η2-Me3SiCtCSiMe3) (M = Ti, L = -; M = Zr, L= THF) as low-valent metal equivalents. The successful isolation of highly reactive metal species with fascinating structural features well accelerated the development in this area. For example, it was demonstrated that zirconacycles with a cumulenic structure could be formed during the coupling process.3,5b Takahashi et al. reported that the reaction of 1,3-butadiynes with a zirconocene-ethylene complex afforded cis-enynes after hydrolysis and R-alkynylcyclopentenones by treatment with CO/I2.4a,b Meunier and co-workers studied the coupling of benzynezirconocene with 1,4-diphenyl-1,3-butadiyne6a and 1,4-bis(trimethylsilyl)-1,3butadiyne.6b In both cases a benzo-fused seven-membered zirconacyclocumulene could be isolated, although in the latter case, a β-alkynylzirconaindene was also isolated as a minor complex. Theoretical calculations revealed that an interaction of the d metal atomic orbital with one terminal σ orbital and with the in-plane π orbital of the cumulene contribute to the remarkable stability of these metal complexes.6a Recently, we (4) (a) Takahashi, T.; Aoyagi, K.; Denisov, V.; Suzuki, N.; Choueiry, D.; Negishi, E. Tetrahedron Lett. 1993, 34, 8301. (b) Takahashi, T.; Xi, Z.; Nishihara, Y.; Huo, S.; Kasai, K.; Aoyagi, K.; Denisov, V.; Negishi, E. Tetrahedron 1997, 53, 9123. (c) Liu, Y.; Sun, W.; Nakajima, K.; Takahashi, T. Chem. Commun. 1998, 1133. (5) For other groups, see: (a) Delas, C.; Urabe, H.; Sato, F. Chem. Commun. 2002, 272. (b) Hsu, D. P.; Davis, W. M.; Buchwald, S. L. J. Am. Chem. Soc. 1993, 115, 10394. (c) Temme, B.; Erker, G.; Fr€ohlich, R.; Grehl, M. Angew. Chem. 1994, 106, 1570. ; Angew. Chem., Int. Ed. Engl. 1994, 33, 1480. (d) Ahlers, W.; Temme, B.; Erker, G.; Fr€ ohlich, R.; Fox, T. J. Organomet. Chem. 1997, 527, 191. (e) Erker, G.; Venne-Dunker, S.; Kehr, G.; Kleigrewe, N.; Fr€ohlich, R.; M€uck-Lichtenfeld, C.; Grimme, S. Organometallics 2004, 23, 4391. (f) Spies, P.; Kehr, G.; Fr€ohlich, R.; Erker, G.; Grimme, S.; M€uck-Lichtenfeld, C. Organometallics 2005, 24, 4742. (6) (a) Bredeau, S.; Delmas, G.; Pirio, N.; Richard, P.; Donnadieu, B.; Meunier, P. Organometallics 2000, 19, 4463. (b) Bredeau, S.; Ortega, E.; Delmas, G.; Richard, P.; Fr€ohlich, R.; Donnadieu, B.; Kehr, G.; Pirio, N.; Erker, G.; Meunier, P. Organometallics 2009, 28, 181. r 2010 American Chemical Society

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Scheme 1

have shown that zirconocene-ethylene-mediated coupling of 1,3-butadiynes with aldehydes or ketones provides an efficient, general, and one-pot method for cis-[3]cumulenols.2d We suggested that the zirconacyclocumulenic intermediates were involved in our reactions.2b We also found the diverse reactivity of zirconacyclocumulenes derived by coupling of benzynezirconocenes with 1,3-butadiynes toward different cyanide compounds such as carbamoyl cyanides or aroyl cyanides, leading to indeno[2,1-b]pyrroles and [3]cumulenones, respectively.2a We also developed a titanium-mediated cis-[3]cumulenol formation in the presence of Lewis acid.2f These results prompted us to examine the reaction with aldehydes. In this paper, we report a direct addition of aldehydes to zirconacyclocumulenes 3, which affords an efficient access to synthetically useful [3]cumulenols with high regio- and stereoselectivity (Scheme 1). We also report the mechanistic insights into this unusual transformation based on DFT calculations.

Table 1. Hydrolysis of Zirconacyclocumulene Complexes

Results and Discussion Hydrolysis of Zirconacyclocumulene Complexes 3 Generated through Coupling of Benzynezirconocene with 1,3-Butadiynes. Zirconocene-aryne complexes, which are easily formed by thermal decomposition of diarylzirconocene derivatives, have been proved to be very useful for the synthesis of a wide range of organic compounds through coupling reactions with unsaturated substrates.7 It was known that the coupling reaction of 1,4-diphenyl-1,3-butadiyne (1a) with benzynezirconocene Cp2Zr(η2-C6H4) occurs by heating 1a with diphenylzirconocene at 80 °C for several hours, furnishing a seven-membered zirconacyclocumulene 3a (Scheme of Table 1, R1 =R2 =Ph).6a It was suggested that 3a might be formed through rearrangement of five-membered Ralkynylzirconaindene (2a).6b Here we found that quenching the reaction mixture with 3 N HCl for 5 min gave rise to 1,10 ,4triphenylbut-3-en-1-yne (4a) in 87% yield, but not cumulene product (Table 1, entry 1).8 The 13C NMR clearly shows two singlets at 89.19 and 93.65 ppm, which are typical for an alkyne unit. Quenching the reaction mixture with 2.2 equiv of MeOH afforded the same product (4a) in 76% yield. When 1,4-bis(4-methoxyphenyl)buta-1,3-diyne (1b) was employed, (7) (a) Buchwald, S. L.; Nielsen, R. B. Chem. Rev. 1988, 88, 1047. (b) Wang, C.; Deng, L.; Yan, J.; Wang, H.; Luo, Q.; Zhang, W.; Xi, Z. Chem. Commun. 2009, 4414. (c) Chen, C.; Xi, C.; Liu, Y.; Hong, X. J. Org. Chem. 2006, 71, 5373. (d) Zhao, C.; Li, P.; Cao, X.; Xi, Z. Chem.;Eur. J. 2002, 8, 4292. (8) The NMR data of 4a are consistent with those reported by Meunier; however, they proposed that the structure of 4a is 1,10 4triphenylbuta-1,2,3-triene. According to NMR spectra of 4a and 2D NMR spectra of 4b (HMQC, HMBC, NOESY) and 4c (NOESY), 4a should be an enyne derivative. (9) In this case, an intermediate was observed upon quenching the mixture in a short time, which could convert to the enyne product during the hydrolysis process. This intermediate was difficult to isolate in pure form due to its instability.

a

Isolated yields. b The reaction mixture was quenched for 30 min.

(Z)-enyne 4b was isolated in 82% yield (entry 2).9 The Z-configuration of the enyne double bond in 4b was determined by the 2D NOESY spectrum. Bisalkyl-substituted butadiynes including those bearing alkoxyl functional groups underwent similar coupling reactions to produce the corresponding (E)- or (Z)-enynes in 72-82% yields after hydrolysis (entries 3-5). When unsymmetrically substituted butadiynes 1f and 1g were employed, regioselective coupling reactions were observed. The corresponding enynes 4f and 4g were obtained as major products in 68% and 73% yield, respectively (entries 6, 7). The structures of 4f and 4g have been confirmed by the 2D NOESY spectrum. The above reactions by simply quenching the zirconium intermediates also provided an efficient method for the stereoselective synthesis of enynes. Reaction of Zirconacyclocumulenes with Aldehydes: Formation of [3]Cumulenols. Next, we proceeded to investigate

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Table 2. Formation of [3]Cumulenols via the Reaction with Aldehydes

a

Isolated yields. Unless noted, all the reactions were carried out using 1 equiv of aldehyde at room temperature for 1-3 h. b Room temperature, 3 h, then 50 °C, overnight. c1.5 equiv of formaldehyde was used. d 50 °C, 3 h, and 1.2 equiv of ethyl glyoxalate was used. e 50 °C, 2 h, and 2.0 equiv of aldehyde was used.

the reactions of zirconacyclocumulenes with aldehydes. Here we found that treatment of the reaction mixture of 3a (R1 = R2 = Ph) with 1.0 equiv of PhCHO at room temperature for 3 h afforded [3]cumulenol 5a smoothly in 83% yield after hydrolysis (Table 2, entry 1). It is noteworthy that the reaction occurred exclusively at the cumulenic zirconium

moiety, whereas the products derived from insertion of a carbonyl group into a Zr-C(sp2) bond adjacent to the fused benzene ring was not detected. The result suggests that this step is highly regioselective. The behavior of zirconacyclocumulene 3 toward aldehyde addition is similar to that of R-alkynylzirconacyclopentenes/zirconacycloheptatrienes, as

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Figure 1. X-ray crystal structure of 5n. Selected bond lengths (A˚) and bond angles (deg): C1-C2 = 1.489(7), C2-C3 = 1.315(7), C3-C4 = 1.271(7), C4-C5 1.348(7), C5-C14 = 1.481(7), C3-C2-C1 = 123.6(5), C3-C2-C7 = 119.3(5), C4-C5-C6 = 120.5(5), C4-C5-C14 = 120.7(5).

we reported recently.2e It should be noted that zirconacycles such as zirconacyclopentadienes and zirconaindenes are generally not reactive toward carbon electrophiles, possibly due to the steric hindrance caused by the bulky cyclopentadienyl ligands and the occupied coordination sites around the metal.10 To achieve C-C bond formation, it always needs transmetalation of the zirconium-carbon bond to another metal-carbon bond such as Cu, Zn, Li, and Ni to increase the reactivity and achieve higher yields.11 In our reaction, however, no transmetalation reagents are required, which indicates that zirconacyclocumulenes are more reactive than normal zirconacycles. The present method could be applied successfully to various types of 1,3-butadiynes and aldehydes to provide the cumulenols 5 in 46-88% yields (Table 2). Aromatic aldehydes bearing electron-withdrawing (-Cl) or electron-donating (-OMe) substituents had no large influence on the product yields, and the desired cumulenols 5b and 5c were isolated in 82% and 85% yield, respectively (entries 2, 3). Bulky substrates, such as 2-bromobenzaldehyde or 1-naphthaldehyde, also smoothly afforded the corresponding products 5d and 5e in good yields (entries 4, 5). Interestingly, the use of 4-(phenylethynyl)phenyl aldehyde or alkynyl aldehyde afforded 5f and 5g in the same yields of 81%, in which the alkyne functionality remained intact (entries 6, 7). The use of formaldehyde gave the corresponding primary alcohol 5h in 77% yield (entry 8). Alkyl aldehyde, such as butyraldehyde, was also compatible (10) (a) Wipf, P.; Jahn, H. Tetrahedron 1996, 52, 12853. (b) Negishi, E.; Takahashi, T. Aldrichim. Acta 1985, 18, 31. (11) For Cu, see: (a) Guo, S.; Liu, Y. Org. Biomol. Chem. 2008, 6, 2064. (b) Liu, Y.; Song, F.; Cong, L. J. Org. Chem. 2005, 70, 6999. (c) Zhou, S.; Liu, D.; Liu, Y. Organometallics 2004, 23, 5900. (d) Xi, C.; Kotora, M.; Nakajima, K.; Takahashi, T. J. Org. Chem. 2000, 65, 945. (e) Lipshutz, B. M.; Wood, M. R. J. Am. Chem. Soc. 1993, 115, 12625. (f) Liu, Y.; Shen, B.; Kotora, M.; Takahashi, T. Angew. Chem., Int. Ed. 1999, 38, 949. (g) Lipshutz, B. H.; Wood, M. R.; Tirado, R. J. Am. Chem. Soc. 1995, 117, 6126. For Zn, see: (h) Lipshutz, B. H.; Wood, M. R. J. Am. Chem. Soc. 1994, 116, 11689. (i) Duan, Z.; Nakajima, K.; Takahashi, T. Chem. Commun. 2001, 1672. For Ni, see: (j) Hauske, J. R.; Dorff, P.; Julin, S.; Martinelli, G.; Bussolari, J. Tetrahedron Lett. 1992, 33, 3715. (k) Takahashi, T.; Tsai, F.; Li, Y.; Wang, H.; Kondo, Y.; Yamanaka, M.; Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 2002, 124, 5059. For Li: see: (l) Seki, T.; Noguchi, Y.; Duan, Z.; Sun, W.; Takahashi, T. Tetrahedron Lett. 2004, 45, 9041. (m) Takahashi, T.; Huo, S.; Hara, R.; Noguchi, Y.; Nakajima, K.; Sun, W. J. Am. Chem. Soc. 1999, 121, 1094.

in this reaction, leading to 5i in 75% yield (entry 9). The ester group could also be easily introduced into the alcoholic position of cumulenol 5j (entry 10). When butadiynes bearing a substituted aryl ring or alkyl-substituted butadiynes were employed, stereoselective formation of cumulenols was observed. In all of these cases, only cis-cumulenols were obtained in 46-75% yields (entries 11-15). When trimethyl(octa-1,3-diynyl)silane (1g) was employed, no reaction was observed with p-chlorobenzaldehyde. The cis-configuration of cumulenols was confirmed by X-ray crystallographic analysis of 5n (Figure 1). However, no reaction occurred of zirconacycle 3a with ketone such as acetophenone. [3]Cumulenes are important substances since they have potential applications in antitumor drug design and as advanced materials, as well as in organic synthesis.12 However, the stereoselective synthesis of cumulenes with reasonable generality is still rare.13,14 Our method provides an efficient and one-pot procedure for the stereoselective synthesis of cumulenes with multifunctionalities. These cumulene derivatives should be attractive substrates for further synthetic manipulations. (12) For selected papers: (a) Wang, K. K.; Liu, B.; Lu, Y. J. Org. Chem. 1995, 60, 1885, and references therein. (b) Skibar, W.; Kopacka, H.; Wurst, K.; Salzmann, C.; Ongania, K.; de Biani, F. F.; Zanello, P.; Bildstein, B. Organometallics 2004, 23, 1024. (c) Bildstein, B. Coord. Chem. Rev. 2000, 206-207, 369. (d) Kinoshita, I.; Kijima, M.; Shirakawa, H. Macromol. Rapid Commun. 2000, 21, 1205. (e) Diederich, F.; Rubin, Y. Angew. Chem., Int. Ed. Engl. 1992, 31, 1101. (f) Furuta, T.; Asakawa, T.; Iinuma, M.; Fujii, S.; Tanaka, K.; Kan, T. Chem. Commun. 2006, 3648. (g) Guan, X.; Shi, M. J. Org. Chem. 2009, 74, 1977. (13) For the synthesis of cumulenes, see: (a) Hopf, H. In The Chemistry of Ketenes, Allenes, and Related Compounds; Patai, S., Ed.; Interscience/Wiley: Chichester, 1980; Part 2, Chapter 20, p 781. (b) Brandsma, L.; Verkruijsse, H. D. In Synthesis of Acetylenes, Allenes and Cumulenes; Elsevier: New York, 1981. (c) Cao, X.-P.; Leung, M.-K. J. Chem. Soc., Perkin Trans. 1 1995, 193. (d) Chow, H.-F.; Cao, X. -P.; Leung, M. -K. J. Chem. Soc., Chem. Commun. 1994, 2121, and references therein. (14) For stereoselective synthesis of disubstituted [3]cumulenes, see: (a) Wakatsuki, Y.; Yamazaki, H.; Kumegawa, N.; Satoh, T.; Satoh, J. Y. J. Am. Chem. Soc. 1991, 113, 9604. (b) Wakatsuki, Y.; Yamazaki, H.; Kumegawa, N.; Johar, P. S. Bull. Chem. Soc. Jpn. 1993, 66, 987. (c) Ohmura, T.; Yorozuya, S.; Yamamoto, Y.; Miyaura, N. Organometallics 2000, 19, 365. (d) van den Hoek, W. G. M.; Kroon, J.; Kleijn, H.; Westmijze, H.; Vermeer, P.; Bos, H. J. T. J. Chem. Soc., Perkin Trans. 2 1979, 4231. (e) Yoshida, T.; Williams, R. M.; Negishi, E. J. Am. Chem. Soc. 1974, 96, 3688. (f) Negishi, E.; Yoshida, T.; Abramovitch, A.; Lew, G.; Williams, R. M. Tetrahedron 1991, 47, 343.

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Figure 2. Optimized five-membered structure 2a, the seven-membered structure 3a, and their isomerization transition state TS-2a-3a. The relative free energies including solvent effect, ΔGsol(298 K), are in kcal/mol (calculated at the B3LYP/6-311þG** level).

DFT Calculations and Mechanistic Aspects. To understand the regioselectivity in the reaction of zirconacycle 2/3 (R1=R2= Ph) with aldehyde, density functional theory (DFT)15 studies have been performed with the GAUSSIAN03 program16 using the B3LYP17 method. For C, H, and O, the 6-311þG** basis set was used; for Zr the Lanl2DZ basis set with effective core potential (ECP)18 was used. For each optimized structure, harmonic vibrational frequency calculations were carried out and thermal corrections were made. All structures were shown to be either transition states (with one imaginary frequency) or local minima (with no imaginary frequency). The solvent effect was estimated (15) (a) Hohenberg., P.; Kohn, W. Phys. Rev. 1964, 136, B864. (b) Kohn, W.; Sham, L. J. Phys. Rev. 1965, 140, A1133. (16) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Frisch, M. J.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannengerg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision D.01; Gaussian, Inc.: Wallingford, CT, 2004. (17) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. 1988, B37, 785. (18) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284. (19) (a) Cances, E.; Mennucci, B.; Tomasi, J. J. Chem. Phys. 1997, 107, 3032. (b) Cossi, M.; Barone, V.; Mennucci, B.; Tomasi, J. Chem. Phys. Lett. 1998, 286, 253.

with the IEFPCM19 (UAHF atomic radii) method in toluene (ε = 2.379) using the gas-phase-optimized structures. Structure of 2a and 3a. First, two possible isomers of the zirconacycle intermediate, 2a and 3a, have been fully optimized (Figure 2). The results indicate that the seven-membered structure 3a is -1.7 kcal/mol more stable than the fivemembered structure 2a. Therefore, 3a should be dominant under room temperature. The transition state of the isomerization from 2a to 3a has also been located (TS-2a-3a). The isomerization barrier is only 4.1 kcal/mol. The low barrier of this isomerization indicates that the seven-membered zirconacyclocumulene may be formed via the five-membered zirconacyclic intermediate.20,6b Both experimental and theoretical studies of the sevenmembered zirconacyclocumulenes have been reported.20,5b,6 The stability of the seven-membered zirconacyclocumulene has been ascribed to the interaction between one of the Zr d orbitals with one terminal σ orbital and the in-plane π orbital of the cumulene.6a The molecule orbital analysis shown in Figure 3 is consistent with this conclusion (Figure 3, HOMO-2). In HOMO-4, the Zr dz2 orbital overlaps with the sp2-hybridized orbital of C1, forming the Zr-C1σ covalent bond. Origin of the Regioselectivity. The transition states for the insertion of aldehyde into the zirconacycle have been explored first with the seven-membered structure 3a since it is more stable than 2a. In the calculation, as the aldehyde becomes close to C6, the seven-membered ring 3a will convert to the five-membered ring 2a before reaching the insertion transition state. This result is also confirmed by the relaxed potential energy surface (PES) scan along the Zr-O (20) Pellny, P.-M.; Kirchbauer, F. G.; Burlakov, V. V.; Baumann, W.; Spannenberg, A.; Rosenthal, U. J. Am. Chem. Soc. 1999, 121, 8313.

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Figure 3. HOMO-2 and HOMO-4 molecular orbitals of 3a (depicted using isodensity at 0.04 au). HOMO-2 is involved in the interaction of C4, C6, and the Zr center. HOMO-4 shows that the C1-Zr σ bond is formed by the overlap of the Zr dz2 orbital with the C1 sp2-hybridized orbital.

Figure 4. Insertion of aldehyde from the left side (Path 1) and the right side (Path 2) of the zirconacycle 2a. TS1 and TS2: The optimized transition states for the insertion reaction. The relative free energies including solvent effect, ΔGsol(298 K), are in kcal/mol (calculated at the B3LYP/6-311þG**/Lanl2DZ level).

and C7-C6 bonds (see the Supporting Information for detail). In 3a, the Zr center is buried deeply; C1 and C6 are shielded more tightly. Therefore the attack of the aldehyde will encounter large steric hindrance. Thus, the five-membered ring is less stable and has higher reactivity. The former

calculation shows that the seven-membered ring and the fivemembered ring are easy to convert to each other. Therefore, as shown in Figure 4, the insertion reaction was studied on the basis of the complex of the five-membered structure 2a and the aldehyde PhCHO (R).

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Organometallics, Vol. 29, No. 13, 2010

Fu et al. Scheme 2

The calculation results show that Path 2 is more favorable; its activation barrier is lower than that of Path 1 by 11.9 kcal/ mol. This result is consistent with the experimental observations. Apparently, if the aldehyde inserts into the Zr-C4 bond, a large steric interaction will be encountered with the alkynyl group. We propose that the steric factor is important to the preference of TS2. As shown in Figure 4, the alkynyl group is sticking out; the attack of C7 to C6 causes only little steric energy. In contrast, in TS1 the aldehyde pushes the Cp rings aside since the Zr-C1 bond is partially shielded by the two Cp rings. In addition, as compared with TS1, the oxygen atom in TS2 coordinated with the Zr center with a shorter distance (2.182 vs 2.272 A˚) and a better angle (the lone pair of the O atom pointing to the Zr center). The product P1, which is not obtained in the experiment, is more stable than the product P2, so this reaction is kinetically controlled. The structure of TS2 indicates that to form a trans product is impossible; therefore, the cis product should be dominant. Considering the experimental data and DFT calculations disclosed above, a possible reaction mechanism for the synthesis of cumulenols is outlined in Scheme 2: First of all, a fast equilibrium between seven-membered zirconacycle 3 and five-membered zirconacycle 2 exists in the reaction mixture, in which 3 is more stable, whereas 2 is more reactive. The addition of a carbonyl group to the propargyl zirconium moiety in 2 proceeds to generate a nine-membered oxazirconacycle 7 via a cyclic synSE20 process,21 and hydrolysis of 7 affords the cumulenol 5. Thus the reaction equilibrium is shifted toward the products.

Conclusion In summary, we have developed an efficient and convenient method for the stereoselective synthesis of tetra-substituted cis-[3]cumulenols through the reactions of aldehydes with zirconacyclocumulenes. An equilibrium between seven-membered zirconacyclocumulene and five-membered R-alkynylzirconaindene is suggesed to exist during the process. The addition of aldehyde to the more reactive zirconaindene intermediate through a cyclic SE20 pathway leads to cumulenol products after hydrolysis. We are currently exploring the new synthetic potential of zirconacycles with cumulenic structures.

Experimental Section Typical Procedure for the Cross-Coupling Reaction of the Zirconocene-Benzyne Complex with Butadiynes. To a suspension of Cp2ZrCl2 (0.19 g, 0.65 mmol) in toluene (5 mL) in a 20 mL Schlenk tube at 0 °C was added dropwise PhLi (1.4 mmol, 2.0 M in dibutyl ether, 0.7 mL) with a syringe. After stirring for 1 h at the same temperature, diyne 1 (0.5 mmol) was added, and the reaction mixture was heated to 80 °C and stirred for 6 h until GC or TLC indicated that the starting material had been consumed. The resulting orange-yellow solution was allowed to return to (21) (a) Marshall, J. A.; Liu, Z.-H.; Johns, B. A. J. Org. Chem. 1998, 63, 817. (b) Marshall, J. A.; Hinkle, K. W. J. Org. Chem. 1996, 31, 105. (c) Urabe, H.; Takeda, T.; Hideura, D.; Sato, F. J. Am. Chem. Soc. 1997, 119, 11295. (d) Hoppe, D.; Kr€amer, T. Angew. Chem., Int. Ed. Engl. 1986, 25, 160.

room temperature, quenched with 3 N HCl solution (usually 5 min), and extracted with diethyl ether. The extract was washed separately with saturated NaHCO3 solution, water, and brine and dried over anhydrous Na2SO4. The solvent was evaporated in vacuo, and the residue was purified by column chromatography on silica gel to afford the desired enyne products 4. (Z)-4,40 -(1-Phenylbut-1-en-3-yne-1,4-diyl)bis(methoxybenzene) (4b). Column chromatography on silica gel (petroleum ether/ ethyl acetate = 20:1) afforded the title compound as a yellow foam in 82% yield. 1H NMR (400 MHz, CDCl3): δ 3.74 (s, 3H), 3.81 (s, 3H), 6.11 (s, 1H), 6.79 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 9.2 Hz, 2H), 7.25-7.32 (m, 7H), 7.52 (d, J = 8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 55.10, 55.13, 88.19, 93.34, 106.24, 112.98, 113.85, 115.78, 128.03, 128.10, 128.14, 131.50, 131.56, 132.71, 141.91, 151.14, 159.31, 159.34. IR (neat): 3010, 2964, 2838, 2552, 2202, 2035, 1881, 1718, 1603, 1584, 1574, 1505, 1464, 1442, 1360, 1244, 1172, 1148, 1105, 1028, 828, 801, 761, 737, 693 cm-1. HRMS (EI): calcd for C24H20O2 340.1463, found 340.1461. Typical Procedure for the Addition Reaction of Aldehydes to Zirconacyclocumulenes. To a suspension of Cp2ZrCl2 (0.19 g, 0.65 mmol) in toluene (5 mL) in a 20 mL Schlenk tube at 0 °C was added dropwise PhLi (1.4 mmol, 2.0 M in dibutyl ether, 0.7 mL) with a syringe. After stirring for 1 h at the same temperature, diyne 1 (0.5 mmol) was added, and the reaction mixture was heated to 80 °C and stirred for 6 h. The resulting orange-yellow solution was allowed to return to room temperature, and aldehyde (0.5 mmol) was added. Then the mixture was stirred at room temperature or 50 °C in some cases until the reaction was complete, as monitored by thin-layer chromatography. The reaction mixture was allowed to return to room temperature, quenched with 1 N HCl solution (usually 5 min), and extracted with diethyl ether. The extract was washed separately with saturated NaHCO3 solution, water, and brine and dried over anhydrous Na2SO4. The solvent was evaporated in vacuo, and the residue was purified by column chromatography on Al2O3 or silica gel or by recrystallization to afford the desired cumulenol products 5. 1,2,5,5-Tetraphenylpenta-2,3,4-trien-1-ol (5a). Column chromatography on Al2O3 (petroleum ether/ethyl acetate=10:1 to ethyl acetate) afforded the title compound as a yellow foam in 83% yield. 1 H NMR (300 MHz, CDCl3): δ 2.83 (bs, 1H), 5.92 (s, 1H), 7.127.56 (m, 20H). 13C NMR (75.5 MHz, CDCl3): δ 73.44, 123.34, 123.88, 126.98, 127.37, 127.61, 127.66, 128.15, 128.34, 128.44, 128.87, 129.46, 136.89, 137.69, 138.42, 142.06, 151.66, 155.87. IR (neat): 3419, 3057, 3028, 1597, 1490, 1443, 1278, 769, 693 cm-1. HRMS (EI): calcd for C29H22O 386.1671, found 386.1666.

Acknowledgment. We thank the National Natural Science Foundation of China (Grant Nos. 20732008, 20821002, 20702059), Chinese Academy of Science, Science and Technology Commission of Shanghai Municipality (Grant No. 08QH14030), and the Major State Basic Research Development Program (Grant No. 2006CB806105) for financial support. Supporting Information Available: Experimental details, NMR spectra of all new products, and CIF files giving crystallographic data of compound 5n, the relaxed potential energy surface (PES) scan, calculated total energies, and geometrical coordinates. This material is available free of charge via the Internet at http://pubs.acs.org.