Could Ionic γ-Elimination Be Concerted: Clocking the Internal Displacement Across a Cyclobutane Ring Uri Habusha, Esther Rozental, and Shmaryahu Hoz* Contribution from the Department of Chemistry, Bar-Ilan UniVersity, Ramat-Gan, Israel 52900 Received September 23, 2002 Abstract: Carbanion 1, obtained by a nucleophilic attack of PhSe - on 3-chlorobicyclobutane-carbonitrile in DME undergoes both protonation and elimination as shown in eq 1. Alcohols of increasing acidity in the following order: t-BuOH, i-PrOH, MeOH, trifluoroethanol (TFE), and hexafluoro2-propanol (HFIP) were used as proton donors. An Eigen-type plot of the log of the product ratio (protonation/elimination) vs the pKa of the alcohols, levels off for the two most acidic alcohols, TFE and HFIP which react at a diffusion- controlled rate. The partitioning of the products between protonation and elimination enables, therefore, the determination of the rate constant for the internal elimination as ∼3 × 10 10 s -1 . Ab initio calculations at the B3LYP/6-31G* level show that the elimination from a model carbanion (4, eq 4) occurs in a barrierless process. Simulation of the experimental reaction by including solvation effects using the Onsager model, shows that using the dielectric constant of DME (7.2) stabilizes, as expected, the carbanion and prevents a spontaneous elimination. In the absence of solvation effects, using Me - as a base, a complete elimination of HCl (proton removal and leaving-group expulsion) took place from 3-chlorocyclobutanecarbonitrile in a barrierless process without the formation of any discrete intermediate. Introduction While in the majority of cases, base promoted -eliminations are concerted, 1 to the best of our knowledge there is not a single report of a concerted γ-elimination reaction. Clearly, the proximity of the nucleophilic and electrophilic centers in -elimination is the reason for the rarity of the stepwise E1cB mechanism 1,2 in such reactions. Since the distance between the reacting centers in γ-elimination is, on one hand, larger than that in -elimination but, on the other hand, smaller than for S N 2 reactions, the relevant question would be: can one engineer a system appropriate for γ-elimination having a distance short enough to promote concertedness? In this contribution we focus on the formation of bicyclobu- tane 3 by bridging across a cyclobutane ring: a case in which the two reaction centers are forced to be relatively close to each other (2.2 Å) in the ground state (in contrast to ca. 2.6 Å in the open chain-propane analogue). Starting with a carbanionic intermediate, as in the E1cB mechanism, our results suggest that, under appropriate conditions, the formation of bicyclobu- tane could occur via a concerted γ-elimination reaction. Results and Discussion. We generated the cyclobutane embedded carbanion 1 by nucleophilic attack of phenylselenolate (PhSe - ) on 3-chlorobi- cyclobutanecarbonitrile (eq 1). In preliminary experiments it was found that the elimination of Cl - to form 2 (eq 1) was accompanied by small amounts (ca. 1%) of the protonation of 1 to yield 3, probably by adventitious water present in the solvent (DME) indicating that the elimination step is not spontaneous but has a measurable barrier. We were therefore interested in determining the lifetime of the carbanionic intermediate 1 which reacts internally to give the bicyclobutane unit. The partitioning of the reaction between the two products paved the way for a clocking experiment 4 in which the rate constant for the elimination could be determined. This approach was attempted previously in a similar case by Jencks et al. who tried to measure the rate constant for the elimination of a thiolate * To whom correspondence should be addressed. E-mail: shoz@ mail.biu.ac.il. (1) Saunders, W. H., Jr.; Cockerill, A. F. Mechanism of Elimination Reactions; Wiley: New York, 1973. (2) Ingold, C. K. Structure and Mechanism in Organic Chemistry; Cornell University Press: Ithaca, New York, 1953; Chapter 8. McLennan, D. J. Quart. ReV. Chem. Soc. 1967, 21, 490-506. (3) For a review of the chemistry of bicyclobutane, see: Hoz, S. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987; Chapter 19. (4) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317. Published on Web 11/21/2002 15006 9 J. AM. CHEM. SOC. 2002, 124, 15006-15011 10.1021/ja028644p CCC: $22.00 © 2002 American Chemical Society