Chair transition state

The Cope rearrangement usually proceeds through a chairlike transition state. The stereochemical features of the reaction can usually be predicted and analyzed on the basis of a chair transition state that minimizes steric interactions between the substituents. Thus, compound 26 reacts primarily ttuough transition state 27a to give 28 as the major product. Minor product 29 is formed flirough the less sterically favorable transition state 27b. 

It is generally assumed that the boat transition state is higher in,energy than the chair transition state. There have been several studies aimed at determining the energy difference between the two transition states. One study involved 1,1,1,8,8,8 eu/cno-4,5-dimethyl-2,6-octadienes. Different stereoisomeric products would be predicted for the chair and boat transition states ... 

Whether or not the highly electropositive alkali metals or magnesium form an ionic instead of a covalent bond to the oxygen of the enolate is less important. Even if there is a contact ion pair of the metal cation and the oxygen anion, the geometry of the six-membered chair transition state, as outlined above, will be maintained. 

This high 1,3-asyrnmetric induction in favor of amine 5 is in accordance with a proposed cyclic chair transition state 7 shown below. 

As a result of additional 1.3-diaxial interactions, involving the C-l position of the allylmetal moiety in the chair transition state 7, a boat transition state 8 has been proposed, to provide amine 6. 

Preference for the chair transition state is a consequence of orbital-symmetry relationships Hoffmann, R. Woodward, R.B. J. Am. Chem. Soc., 1965, 87, 4389 Fukui, K. Fujimoto, H. Tetrahedron Lett, 1966, 251. 

It will be seen that the chair transition state (9) is predicted to be more stable than the boat (8) by 6.5 kcal/mole the experimental evidence implies 29) that 9 is favoured by not less than 5.7 kcal/mole . The experimental value is based 29) on the presence of a very small amount of product (< 1%) that could have been formed via 8 since the amount was so small, this was identified only by its g.l.c. retention time. If the identification was correct, the ratio of products implies a difference in activation energy of 5.7 kcal/mole between 8 and 9 our calculations suggest that the identification was correct and that Doering and Roth were overcautious. 

The basic assumption of the chair-preferred transition state (for tetrahedral metal centers) is clearly tenuous, and diastereomeric boat transition state geometries should not be discounted. For example, the diastereomeric chair and boat transition states for (Z)-enolates are illustrated in Scheme 4, For this enolate geometry it is entirely reasonable to consider that the heat of formation of boat transition state B2 might actually be less than chair transition state C4 for certain combinations of substituents Ri, R2, and R3. For example, boat transition state B2 not only disposes substituents R2 and R3 in a staggered conformation as in chair transition states C3 and C4, but also minimizes Rj R3 eclipsing, which must be significant in chan-transition state C3. The change in kinetic aldol diastereoselection of... 

RiCOEt appear to have a cooperative influence. As noted earlier these trends are fully consistent with the predictions made by a consideration of diastereomeric chair transition states (Scheme 3) involving boron and not the alternate boat geometries (Schemes 4 and 6). 

For the cyclization of diazo ester 32 there are four competing diastereomeric chair transition states leading to CH2 insertion products. In the transition state, the Rh-C bond is aligned with the target C-H bond leading to C-C bond formation. The two most stable of these transition states are depicted in Scheme 16.8. The actual product from cyclization is determined as the intermediate carbenoid commits to a particular diastereomeric transition state. If the C-C distance is short at the point of commitment (tight transition state), there will be a substantial steric interaction between the arene and the ester, and 32 b will be disfavored. If the C-C distance is longer, this interaction will not be as severe and more of 32 a will be formed. Thus, it seems reasonable that the ratio of 3 a to 36b is a measure of the C-C bond distance at the point of commitment of the rhodium carbenoid. 

From these and related examples, the following generalizations have been drawn about kinetic stereo selection in aldol additions.9 (1) The chair transition-state model provides a basis for explaining the stereoselectivity observed in aldol reactions of ketones having one bulky substituent. The preference is Z-enolate —> syn aldol E-enolate —> anti aldol. (2) When the enolate has no bulky substituents, stereoselectivity is low. (3) Z-Enolates are more stereoselective than E-enolatcs. Table 2.1 gives some illustrative data. 

The Cope rearrangement is the conversion of a 1,5-hexadiene derivative to an isomeric 1,5-hexadiene by the [3,3] sigmatropic mechanism. The reaction is both stereospecific and stereoselective. It is stereospecific in that a Z or E configurational relationship at either double bond is maintained in the transition state and governs the stereochemical relationship at the newly formed single bond in the product.137 However, the relationship depends upon the conformation of the transition state. When a chair transition state is favored, the EyE- and Z,Z-dienes lead to anli-3,4-diastereomcrs whereas the E,Z and Z,/i-isomcrs give the 3,4-syn product. Transition-state conformation also... 

Because of the concerted mechanism, chirality at C-3 (or C-4) leads to enantiospecific formation of new chiral centers at C-l (or C-6).138 These relationships are illustrated in the example below. Both the configuration of the new chiral center and that of the new double bond are those expected on the basis of a chairlike transition state. Because there are two stereogenic centers, the double bond and the asymmetric carbon, there are four possible stereoisomers of the product. Only two are formed. The /i-double-bond isomer has the S-configuration at C-4 whereas the Z-isomer has the -configuration. These are the products expected for a chair transition state. The stereochemistry of the new double bond is determined by the relative stability of the two chair transition states. Transition state B is less favorable than A because of the axial placement of the larger phenyl substituent. 

The stereochemistry of the silyl enol ether Claisen rearrangement is controlled not only by the stereochemistry of the double bond in the allyhc alcohol but also by the stereochemistry of the silyl enol ether. For the chair transition state, the configuration at the newly formed C—C bond is predicted to be determined by the E- or Z-configuration of the silyl enol ether. 

Finally, it should be mentioned that Suzuki et al. have aheady remarked the correlation existing between ketone flexibility and axial attack. Vails, Toromanoff and Mathieu have also underlined the importance of antiperiplanar attack, although their interpretation is different from ours and stresses the low energy content of the pre-chair transition state. 

The reaction is 100% stereoselective and affords 69 as a unique stereomer with the (/f)-configuration at C-6, assigned by X-ray analysis. Consequently, the configuration at C-6 results from the well-known chair transition state model for the (Z)-O-allyl enol 68 in which the aUyl unit is on the opposite side to the isopropylidene ketal at C3-C4 and reacts on the Si face of the trisubstituted carbon-carbon double bond. Such a transition state leads to the sole (/ )-configuration in 69. 

The asymmetric inducting effect of the chiral pyranic ring placed outside of the six centers of the chair transition state has to be noted. In the present case, magnesium dihalide seems to play a crucial role in terms of stereocontrol as an efficient tool to fix a defined... 

A biochemically significant Claisen rearrangement is the transformation of choris-mate into prephenate [232] via a chair transition state. Although it is impossible to settle the question of the direction of electron flow during the reorganization, that shown by the arrows in the formula should be preferred when the influence of the various substituents is considered. 

An analysis of the steric effects in a chair-transition state for the reaction ... 

The preferred chair transition state geometry by FMO theory ... 

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