Stereoelectronic effects summary

In summary, we completed the total syntheses of (-)-mniopetal F (6) and (-)-kuehneromycin A (7) in their natural forms. Our total synthesis feature a the highly ewdoselective IMDA reaction using some substrates carrying a trialkylsilyloxy group at C-l. The n-facial selectivity in the IMDA reaction was controlled by the stereoelectronic effect of the silyloxy group adjacent to the dienophile part. 

The dominant contributor to the reactivity of vinylcyclopropanes in any radical reaction is the form (4a), the cyclopropylcarbinyl radical system. The opening of a cyclopropylcarbinyl radical to a butenyl radical is among the fastest radical processes known, with a rate constant of 1.3 x 10 sec". - The various stereoelectronic effects of this rearrangement have been reviewed. The structure of (4a), deduced from its ESR spectrum - and in agreement with calculations (STO-36 basis set), is in the bisected conformation shown, predicted to be 1.4 kcal mol more stable than its perpendicularly oriented counterpart. Above -KX) T only the butenyl radical (4b) can be detected. Substituent efiects do not seem to operate here when the substituents are on the cyclopropane (i.e. product stabilization). The cy-clopropylcaibinyl cation and anion have structures similar to (4a), bisect conformations (5) and (6), respectively. A concise summary of solvolytic and mechanistic data for system (5) has recently appeai Reviews of cyclopropylcarbinyl anions and carbenes are also available. - ... 

In summary, the anti diol should cyclize faster than the syn when steric effects are the only controlling factor in the reaction. If both aUylic 1,3-strain and stereoelectronic effects are involved, then the syn diol should react more rapidly. 

In the case of the six-membered ring orthoester 207 (Fig. 8.48), the ester alcohols 213 and 214 are obtained in 1 1 ratio. Since the diol 212 is not present in the hydrolysate, it is reasonable to conclude that cations 208 and 209 do not contribute to the hydrolysis route and that the products 213 and 214 come only from the cyclic cation 210. In summary, all hydrolysis processes involve the cyclic cations 201 (R = Me or Ph) and 210, whereas the cation 200 issued from seven-membered ring opening is only observed when R is methyl substituent. These results are now rationalized in the light of stereoelectronic effects and with the help of theoretical calculations. 

Summary Although this chapter has outlined a wide variety of stereoelectronic interactions across the broad spectrum of functional groups, these effects can be summarized within several well-defined classes of interactions (0/0, o/x //x/o, n/o, n/x and x/x ). Most of these interactions are relatively weak and can be switched off or on by rotation. However, the combination of the best donor (lone pair) and the best acceptor (a x -orbitals) can lead to situations where rotation is significantly inhibited at room temperature. Stereoelectronic effects of a different nature can coexist and lead to multiple layers of consequences for stracture and reactivity. 

In summary, this chapter has discussed stereoelectronic effects on reactivity and stability which benefit from the rigid preorganization and closer spatial orbital proximity imposed by the presence of a double bond between the donor and acceptor orbitals. 

Summary The recurring theme in the above examples is that a minor delocalizing interaction can be inactive at the most stable ground state geometry defined by an alternative stronger interaction that moves the system perpendicularly to the desired reaction coordinate. The stereoelectronic readjustment requires a conformational change and comes with a thermodynamic cost. When such readjustment is unnecessary, the role of stereoelectronic effects is revealed clearly and their accelerating power is ntihzed fully. 

In summary, the stereochemical course of cation-7t cyclizations is determined by stereoelectronic and conformational effects. Concerted cation-Ti cyclizations usually involve a stereospecific trans-addition (axial attack) of the carbocation to the double bond. This is exemplified by Johnson s biomimetic synthesis ( )-progesterone, which possesses a trans, anti, trans-fused ring system." - ... 

Summary The collection of examples and concepts provided in this chapter illustrates that timing of stereo-electronic interaction determines their effects on reactivity. Delocalizing interactions can be counterproductive when they fade out of existence along the reaction path or productive/accelerating when they are amplified in the transition state. In the following sections, we will provide further examples of dynamic stereoelectronic interplay between structure and reactivity in a variety of chemical areas. 

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