Unexpected Regiochemistry in the Benzannulation Reaction of Fischer Carbene Complexes in the Synthesis of Cyclophanes

The benzannulation reaction of Fischer carbene complexes with alkynes is one of the most versatile methods for the construction of substituted phenols. 1 The two possible regiochemical outcomes that have previously been observed are illustrated in 4-methoxyphenols 2a and 2b which differ in the direction of alkyne incorporation. The regiochemistry of alkyne incorporation is normally controlled by the steric differential between the two substituents of the alkyne 2,3 and the largest substituent is preferentially introduced adjacent to the phenol function, as illustrated in 2a. The disconnection for the overall process is indicated in the assembly of the three subunits in 3. We report here the observation of phenol 4, a new regioisomer for this reaction which was unanticipated since its formation would formally require the breaking of the carbon -carbon bond between the carbene -carbon and the carbon-bearing substituent R 1 in complex1. The overall assembly of the pieces in the formation of phenol4 is indicated in5 where the vinyl group of the starting carbene complex is incorporated in a fashion that is reversed from normal phenols2a and2b.We recently reported that â-tethered vinyl chromium carbene complex 6 would undergo an intramolecular benzannulation with incorporation of the tethered terminal alkyne to givem-cyclophane8b in 58% yield.4,5 This method gives synthetically useful yields of m-cyclophanes and has been examined for tether lengths up to 17 methylenes with no dropoff in yield (60% yield forn ) 17). Them-cyclophane8b was expected from this reaction on the basis of the regiochemistry observed for intermolecular reactions, which give phenol 2a as the major isomer with the larger substituent of the alkyne incorporated adjacent to the phenol function. The same analysis leads to the expectation that R-tethered complexes of the type 13 would lead to the formation of p-cyclophanes14. Complexes13were prepared in two steps from the R,ω-diynes 11 as outlined in Scheme 2. Bromoboration with 1 equiv of 9-bromo-9-BBN and subsequent hydrolysis gave a statistical mixture of products from which the bromoenyne 12 could be readily separated. 6 Attempts to generate the dianion of 12 by reaction with 2 equiv of butyllithium or 3 equiv oftertbutyllithium failed to give any significant yield of the desired carbene complex. 7-9 This problem was solved by deprotonation of 12 with phenyllithium and then subsequent metal halogen exchange withtert-butyllithium to give the dianion of 12,which underwent selective reaction with chromium hexacarbonyl by the vinyl anion. As anticipated,p-cyclophane14b was isolated from the intramolecular benzannulation of complex 13b accompanied by a nearly equal amount of [10,10]p,p-cyclophane16b. However, the major products of the reaction were [10]m-cyclophane8b and bicyclo[3.1.0]hexenone 15b.The formation ofm-cyclophane 8b from this reaction was particularly surprising since this is the † Current address: Department of Chemistry, Michigan State University, East Lansing, MI 48824. (1) For recent reviews on carbene complexes in organic chemistry, see: (a) Wulff, W. D. In Comprehensi Ve Organometallic Chemistry II ; Abel, E. W., Stone, R. G. A., Wilkinson, G., Eds.; Pergemon Press: New York, 1995; Vol. 12, p 469. (b) Bernasconi, C. F . Chem. Soc. Re V. 1997, 26, 299. (c) Hegedus, L. S. Tetrahedron1997, 53, 4105. (d) Wulff, W. D.Organometallics 1998, 17, 3116. (e) Do ̈tz, K. H.; Tomuschatt, P. Chem. Soc. Re V. 1999, 28 187. (f) Herndon, J. W. Coord. Chem. Re V. 1999, 181, 177. (g) Dörwald, F. Z. Metal Carbenes in Organic Synthesis ; Wiley-VCH: New York, 1999. (2) (a) Wulff, W. D.; Tang, P. C.; McCallum, J.. Am. Chem. Soc. 1981, 103, 7677. (b) Do ̈tz, K. H.; Mühlemeier, J.; Schubert, U.; Orama, O. J. Organomet. Chem. 1983, 247, 187. (c) Yamashita, A.; Toy, A. Tetrahedron Lett. 1986, 27, 3471. (3) (a) Chamberlin, S.; Waters, M. L.; Wulff, W. D. J. Am. Chem. Soc. 1994, 116, 3113. (b) Brandvold, T. A.; Wulff, W. D.; Rheingold, A. L. J. Am. Chem. Soc. 1991, 113, 5459. (c) Brandvold, T. A.; Wulff, W. D.; Rheingold, A. L.J. Am. Chem. Soc. 1990, 112, 1645. (4) Wang, H.; Wulff, W. D.J. Am. Chem. Soc . 1998, 120, 10573. (5) For an additional example, see: Do ̈tz, K. H.; Gerhardt, A.J. Organomet. Chem. 1999, 578, 223. (6) Hara, S.; Dojo, H.; Takinami, S.; Suzuki, A. Tetrahedron Lett . 1983, 24, 731. (7) Reaction of12a with 1 equiv of NaH or EtMgBr and then 2 equiv of tert-butyllithium failed to give more than 2% of 13a. (8) For successful related transformations, see: (a) Barluenga, J.; Sanz, R.; Fananas, F. J. Chem. Eur. J.1997, 3, 1324. (b) Henniges, H.; Meyer, F. E.; Schick, U.; Funke, F.; Parson, P. J.; de Meijere, A. Tetrahedron1996, 52, 11545. (c) Furber, M.; Taylor, R. J. K. J Organomet. Chem . 1986, 311, C35. (9) This failure may be related to observations made with haloaryl acids: Beak, P.; Musick, T.; Chen, C.-W . J. Am. Chem. Soc . 1988, 110, 3538. Scheme 1