Vicinal quaternary centers

A synthetic approach to hyperevolutin A 421, prenylated bicyclo[3.3.1] nonanone derivative, with an acylated phloroglucinol-type fragment, has been described (464). Intramolecular allene-nitrile oxide cycloaddition of 422 has been used to construct the bicyclic framework and the vicinal quaternary centers in cycloadduct 423. 

Ng, D., Yang, Z., and Garcia-Garibay, M.A. (2004) Total synthesis of ( )-herber-tenolide by stereospecific formation of vicinal quaternary centers in a crystalline ketone. Organic Letters, 6, 645-647. 

Claisen rearrangement. The Claisen rearrangement of highly substituted allyl vinyl ethers can proceed readily even when two vicinal quaternary centers are formed. Thus addition of an allylic Icohol (1) to an allenic sulfone (2) provides the allyl vinyl ether... 

Even highly functionalized systems with vicinal quaternary centers can be prepared very readily. 

The first chemical synthesis of an optically active trichodiene, (-)-trichodiene involved a Claisen-lreland rearrangement as the key step to connect the vicinal quaternary centers. J.C. Gilbert and co-workers found that the rearrangement occurred with complete facial selectivity and excellent diastereoselectivity to afford an advanced intermediate that was directly converted to (-)-trichodiene. 

Denmark, S. E., Harmata, M. A. Carbanlon-accelerated Clalsen rearrangements. 3. Vicinal quaternary centers. Tetrahedron Lett. 1984, 25, 1543-1546. 

The carbanion -accelerated Claisen rearrangement is also a viable reaction for the creation of vicinal quaternary centers, as shown, e.g., by the rearrangement of 193 to 194 164 c). A similar carbanion -accelerated Claisen rearrangement of 197 could... 

The sodium salt of the JV-methoxycarbonyl hydrazone rearranges faster than the hydrazone itself or the parent ketone. This method has been used for the construction of vicinal quaternary centers, since the accelerating functionality can simply be removed by Wolff Kischner reduction. For charge-accelerated Claisen rearrangements of related systems see refs 85 and 113— 118. 

In another approach to the preparation of communesins, AdUngton and George [26] also utilized what is believed to be an intramolecular IDA cycloadditiOTi reaction of an aza-orf/io-xylylene with an W-methyl-indole (compound 40) as a key synthetic step, this time producing a pentacyclic structure 43 which contains both of the vicinal quaternary centers present in the communesin scaffold, albeit in modest yield (Scheme 12). Two additional side products 41 and 42 (possibly resulting from an electrocyclic reaction involving the vinyl group, or attack by imidazole on the terminal alkene) were also isolated. It should be noted that an alternative mechanism for the formation of the three products, which involves an allylic carbocation species (39), can also be postulated. 

Perophoramidine (18) shares the same connectivity as the communesins, but 18 contains a bis-amidine rather than the bis-aminal functionality present in 15-17. The trans- rather than the c/s-stereochemical relationship of the vicinal quaternary centers is another distinguishing feature. Moreover, 18 lacks the azepine ring system of communesin A, and 18 contains two chlorines on the aromatic ring [28]. 

The 5-exo intramolecular Heck reaction has been employed to construct both meso-chimonanthine 105 and (-)-chimonanthine 106 (Scheme 16). The synthetically most challenging structural features of these bispyrroloindoline alkaloids are their vicinal quaternary centers. The synthetic plan relies on two sequential 5-exo carbopallada-tions to stereoselectively produce pentacycles 102 and 104 from closely related intermediates. Heck cyclization of 100 requires a challenging tetrasubstituted alkene insertion to provide 101. A second 5-exo carbopalladation reaction adjacent to the newly formed quaternary center installs the second quaternary center and oxindole unit. The tartrate-derived ene-diamide 100 underwent bis-5-cJct) carbopalladation when... 

---