Point of Commitment

The major diastereomer seen with each of the rhodium(II) catalysts surveyed was 36a, leading to 41a (Tab. 16.7). For the TFA catalyst (entry 5) a significant proportion 

5 Conclusions Implications for the Design of an Effectively Chiral Catalyst 

We had expected that we might observe some correlation between two or more of these four measures of reactivity, but in fact plots of one versus the other showed no such correlation. We project that the study outlined here will lay the basis for a more detailed understanding of the mechanism of rhodium-mediated intramolecular C-H 

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On the basis of these parameters we determined two possible transition states, 22 and 23. In transition state 22, the rhodium carbene is pointed away from the flip of the incipient cyclopentane ring (a chair-like transition state, counting the five carbons and the rhodium in the six-membered ring), whereas in 23 the rhodium carbene is pointed toward the flip of the incipient cyclopentane ring (a boat-hke transition state). As 10 (see Scheme 16.3) cyclizes to 12, in which the methyl and the phenyl are on the same face of the cyclopentane, we concluded that at the point of commitment to product formation, the transition state leading to cyclization must be chair-like 22 rather than boat-like 23. 

We propose that there is in fact a substantial electronic preference, not reflected in the Mechanics calculations, for the ester carbonyl and the C=Rh bond to be syn at the point of commitment to cychzation. This preference is strong enough to overcome the calculated steric preference (3.37 kcal moh ) for the anti transition state. The competition then, is between the syn transition state leading to (R,R)-29, and the syn transition state leading to (S,S)-29. The relative energies of these two transition states differ by slightly less than 1 kcal moh, so we predict, and observe, low diastereoselectivity. 

Comparing and Contrasting Rhodium Cataiysts Four Dimensions of Reactivity 369 16.4.1.4 Distance at the Point of Commitment... 

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. 

Scheme 16.8 Transition states for the CH2 insertion. The distances at the point of commitment are indicated by braces.

Long term and sometimes lethal side effects also come in the form of self-inflicted injuries due to poor judgement while under the influence of psilocybin. As sensitivity to pain is decreased, the users may not know they are hurting themselves until later. In other instances, the users can overestimate their abilities and attempt something like trying to jump from extreme heights or walk on water. Occasionally, users under the influence of psilocybin become distressed to the point of committing suicide. 

The power of Rh-mediated intramolecular C-H insertion can be seen in the cycli-zation of the a-diazo ester 1 (Scheme 1). Although four diastereomers could have been formed from this cyclization, only 2, the key intermediate for the synthesis of the dendrobatid alkaloid 251F 3, was in fact observed. This outcome, as explained in detail shortly, had first been predicted computationally. This chapter summarizes our computational approach toward understanding the transition state ( point of commitment ) for these Rh-mediated cyclizations. As we discuss at the end of this chapter, there is yet much left to be learned. 

While we have had some success, we are aware of the limitations inherent in a transition-state model for rhodium-mediated C-H insertion that attempts to predict product ratios on the basis of mechanics calculations. Arbitrary decisions limiting the several degrees of freedom possible in the transition state could lead one to a model for the point of commitment to cyclization that would be far from reality. The work described here is important because it offers experimental evidence for a key rotational degree of freedom, the dihedral angle between the ester carbonyl and the rhodium carbenoid. 

What does the fulcrum represent in a supply chain The fulcrum is the point at which we commit to source/produce/ship the product in its final form and where decisions on volume and mix are made. The idea being that if that point of commitment can be delayed as long as possible then the closer we are to make-to-order, with all the benefits that brings. 

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