[Molecules: 16] [Related articles/posters: 023 114 056 065 002 ] |
The extension of these findings subsequently led us to discover that an allylic zinc reagent bearing an anionic bis-oxazoline ligand takes place with excellent enantioselectivity (eqn. 2).[2] For instance, the reaction of the cyclopropenone acetal 3 with an allylic zinc bromide in the presence of one equivalent of the anionic bis-oxazoline ligand 2a proceeded smoothly at room temperature to afford the cyclopropanone acetal 4 in high yield with the enantioselectivity better than 98% ee. On the other hand, in the reaction of substituted allylic zinc reagents, e.g., cinnamyl zinc reagent, both the enantioselectivity and the 1,2-diastereoselectivity for the newly formed C-C bond eroded rather mysteriously. Interpretation of the mixed success and the resolution of these problems by analysis with pencil and paper appeared to be difficult since very little was known of the nature of the olefin carbometalation reactions. We thus felt it necessary to obtain molecular-level understanding of the stereochemistry of allylmetalation of olefins by computational analysis. By following the protocol we established previously for carbometalation reactions with organolithium and copper reagents,[3] we first analysed the reaction with ab initio calculations for simple models, and then with semiempirical methods for larger systems. By taking advantage of the capability of electronic publication to handle 3D pictures, we present herein our computational studies graphically displaying various transition structures in olefin allylmetalation reactions.
The addition of a substituted allylic zinc reagent creates an issue of mutual face selection for the two olefinic faces of both reactants, that is, 1,2-diastereoselectivity concerning the newly formed C-C bond. The reaction of substituted allylic zinc reagents 9, 10 and 11 were thus examined in the presence of anionic bis-oxazoline ligand (2a or 2c) as shown in eqn. (4). As summarized in Table 1, the diastereoselectivity for crotylzinc reagent 9, cinnamyl reagent 10 and perhydrocinnamyl reagent 11 was moderate (72:28, 73:27 and 83:17, respectively) and when the anionic bis-oxazoline ligands 2a and 2c was used. The use of tert-butyl substituted ligand as in 11 did not improved the 1,2-diastereoselectivity (entries 3 and 4) while it greatly improved the enantioselectivity from 62 to 97%.
The 1,2-diastereoselectivity of the addition of a metal enolate or an allylic metal reagent to a carbonyl group conventionally calls for chair and boat transition states.[4] On the other hand, we have reported previously in a preliminary form that the allylmetalation of isolated C-C double bond and triple bond may proceed through a single half chair transition state. We thus suspected that the flexibility of the half chair transition state may be the reason for the erosion of the selectivity, and started to investigate the details of the transition state first at the ab initio level for simplified model systems and then at the semiempirical level for more realistic models.
Figure 1 Two configurationally different transition structures of the addition of allylzinc chloride to cyclopropene at the HF/3-21G level
Solvent effects were then investigated by adding one molecule of water (a model for an ethereal solvent) on the metal so that coordinative saturation is achieved (Figure 2). It is notable that solvation does not affect much the gross molecular geometry of the TSs, only elongating the forming C4-C5 and C1-Zn bond by 1-2%. Apparently, the electronic background that determines the basic half chair conformation (vide supra) is strong enough not to allow large structural perturbation by a solvent molecule. The relative energy of the two TSs was however raised slightly to 1.29 kcal mol-1, suggesting that solvation may significantly affect the stereoselectivity.[10].
Figure 2 Two configurationally different transition structures of the addition of allylzinc chloride to cyclopropene in the presence of a H2O molecule at the HF/3-21G level
Finally, the reaction of water-solvated crotylzinc chloride with cyclopropene was studied. We also found two TSs of nearly equal energy as shown in Figure 3. The calculated energy difference (0.369 kcal mol-1) at this level of approximation of solution reactions should be viewed as negligible, yet some important characteristics were noted. First, only the half-chair TSs are available for the reaction as in the previous models. Secondly, there may occur some torsional strain for the forming C3- C4 bond in TS E (indicated by an arrow) which may slightly destabilize this transition structure. In TS F, on the other hand, the short distance (2.593 angstrom) between the two asterisked hydrogens suggests that TS F would be significantly destabilized if H** is replaced by an alkoxy group as in our substrates CPA 3.
Figure 3 Two configurationally different transition structures of the addition of trans-crotylzinc chloride to cyclopropene in the presence of a H2O molecule at the HF/3-21G level