Allyl cations configurational stability

One major task is the selection of the optimal cation" for a given carbanion . It determines to a great extent the mechanism of the reaction and the positional and configurational stability of the allyl moiety, and thus, the regioselectivity, EjZ selectivity, and diastereoselectivity. Some reviews cover these topics in general1 " 5. 

Terpene synthases, also known as terpene cyclases because most of their products are cyclic, utilize a carbocationic reaction mechanism very similar to that employed by the prenyltransferases. Numerous experiments with inhibitors, substrate analogues and chemical model systems (Croteau, 1987 Cane, 1990, 1998) have revealed that the reaction usually begins with the divalent metal ion-assisted cleavage of the diphosphate moiety (Fig. 5.6). The resulting allylic carbocation may then cyclize by addition of the resonance-stabilized cationic centre to one of the other carbon-carbon double bonds in the substrate. The cyclization is followed by a series of rearrangements that may include hydride shifts, alkyl shifts, deprotonation, reprotonation and additional cyclizations, all mediated through enzyme-bound carbocationic intermed iates. The reaction cascade terminates by deprotonation of the cation to an olefin or capture by a nucleophile, such as water. Since the native substrates of terpene synthases are all configured with trans (E) double bonds, they are unable to cyclize directly to many of the carbon skeletons found in nature. In such cases, the cyclization process is preceded by isomerization of the initial carbocation to an intermediate capable of cyclization. 

The asynchronous way of a-oxide splitting is observed only when the arising cation centre is stabilized by a- or -participation The direction of the skeletal shift in such systems is determined only by the configuration of the breaking bond and does not depend on the structure of the syn-located bridge this factor, however, exerts an essential influence on the composition of the reaction products which also depends on the nature of the acid and on the reaction conditions. In all these rearrangements no products of homo-allylic conjugation with the double C —C bond are formed. 

A wide range of transition metal-allyl complexes are known to react with many types of nucleophiles. In most cases, these reactions occur between cationic allyl complexes and amines or stabilized, anionic carbon nucleophiles. The reaction typically occurs between the nucleophile and the form of the allyl complex, and attack usually occurs at the face of the allyl ligand opposite the metal. However, there are exceptions to these trends. For example, several experiments suggest that unstabilized carbon nucleophiles react first at the metal center, and C-C bond formation occurs between the alkyl and the allyl group by reductive elimination. In addition, a recent study has shown through deuterium labeling that attack of malonate anion on a molybdenum-allyl complex occurs with retention of configuration. ... 

It is of interest to note that artemisia alcohol (18) produced in the hydrolysis of 16-OPy I" is essentially completely racemic (>98%) (57). Apparently (18) is formed by nucleophilic capture of the acyclic allylic carbonium ion (29) rather than direct attack in the 3 position of the chrysanthemyl carbonium ion (28). Nucleophilic substitution upon cyclopropylcarbinyl cations to give homoallyl products occurs with inversion of configuration 74—75). In the case of (28), however, position 3 is highly hindered by the adjacent gem dimethyl groups thus collapse to the allylicly stabilized (29) is faster than direct substitution. The formation of a small amount of cw-chrysanthemol (27, 0.25%) is taken to indicate that allylic ion (29) recyclizes, at least in part, back to (28) and its cis isomer (30). 

---