Addition reactions assisted isomerization

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. 

Our group recently showed that addition of I2 to chelated Pt(II) diaryl complexes resulted in the formation of free iodoarene and Pt(II) aryl iodo complexes, with the exception of the small dmpe ligand system, where stable oxidative addition Pt(IV) complex fra y-(dmpe)Pt(Ar)2l2 was isolated (Scheme 26) [70]. Heating this complex in polar solvents gave the mixture of products the thermodynamically stable cis-isomer and Ar-I reductive elimination products (Scheme 27a) [71]. The isomerization reaction was light-assisted with the light triggering the diphosphine chelate... 

The conversion of the allylic enantioface is most likely to proceed via the tx riHCO-octadienediyl-Ni" transition state TSefc[2] (Fig. 5). In accordance with evidence provided from both experimental [17,18] and theoretical [19] studies, allylic isomerization is most Ukely to occur via the ix, ri (C )-octa-dienediyl-Ni" transition state TSiso[3], which constitutes the internal rotation of the vinyl group around the formal C -C single bond (Fig. 5). The explicit investigation of monomer-assisted reaction paths revealed that additional ethylene or butadiene does not accelerate either allyhc isomerization or enantioface conversion by coordinative stabilization of the corresponding transition state. 

More recently, the first direct observation of C-O oxidative addition of an aromatic elher to a transition metal complex has been reported by Kakiuchi (Equation 4.76). This reaction occurs by initial chelate-assisted C-H bond cleavage, followed by isomerization to form the final Ru(II) aryloxide complex. 

The bicyclo[2.2.0]but-l(3)-enes belong to the latter class. As systematic investigations by Gunter Szeimies have disclosed, tricyclo[4.1.0.0 ]hept-l(7)-ene acts as a turntable in the reactions of alkyl- and aryllithiums with 1-chlorotricyclo[4.1.0.0 ]heptanes (Scheme 1-219). Lithium aziridine is basic enough to sustain such a sequence of metaiation, elimination, and nucleophilic addition. The A-tricycloheptylaziridine thus formed thermolyses at 150 °C to cyclohex-2-ene-l-carbonitrile. The weekly basic lithium benzenethiolate requires the assistence of LITMP to accomplish the deprotonation step before it can add smoothly to give the intermediate 276 (Scheme 1-219). Dienes rather than nucleophiles may be also used to trap strained bicyclo[2.2.0]but-l(3)-enes like 276. Such species may also be generated from l-bromo-7-(trimethylsilyl)tricyclo[4.1.0.0 ]heptanes and cesium fluoride in DMSO at +25 °C. At elevated temperatures (about +100 °C), the bicyclobutene 276 isomerizes rapidly to 1,3,5-cycloheptatriene by [2+2]-cycloelimination. ... 

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