Quaternary carbon centers sesquiterpenes

The presence of a quaternary carbon atom is frequently encountered in sesquiterpene natural products and it often creates a synthetic challenge when two or more quaternary carbon atoms are present contiguously. The synthetic strategies for the construction of quaternary carbon centers involve sigmatropic rearrangements/ intramolecular cycloaddition/ and the reaction of tertiary carbon nucleophiles with a carbon electrophile. Recently, radical cyclization strategies turned out to be very effective for this purpose. For example, Srikrishna utilized the radical cyclization reaction to prepare tricyclo[6.2.1.0 - ]undecane system, which is present in several sesquiterpenes such as zizaenes and prelacinanes, and Chen demonstrated that a tandem radical cyclization approach is an efficient method for constructing the two quaternary carbon centers in the cedrene skeleton. ... 

Based on preliminary results in the model studies, we turned our attention to the synthesis of zizaene sesquiterpenes such as d/-zizaene, /-isokhusimone, and d/-khusimone. To construct the zizaene skeleton via the consecutive carbon-carbon bond formation approach, the disconnection of two bonds of the four bonds at the quaternary carbon center of the ring junction should be possible as shown in Figure 12. Approaches d and e are not promising due to the involvement of 8-and 10-membered ring intermediates, whereas approach c requires stereocontrol at three stereogenic centers. In approach b, difficulty in... 

Although only a few examples have been reported for the consecutive carbon-carbon bond formation approach in cyclization reactions [30], A-aziridinylimines are ideally suited for the construction of quaternary carbon centers. Based on the consecutive carbon-carbon bond formation approach, several sesquiterpenes (Fig. 2) have been synthesized. In order to demonstrate how to execute the synthesis using the consecutive carbon-carbon bond formation approach, the synthesis of DL-zizaene is discussed [31]. 

A [3,3]-sigmatropic rearrangement/RCM sequence [2] was also used as a key step in the total synthesis of a bioactive spirobenzofuran 7 isolated from the mycelium cultures of Acremonium sp. HKl 0230 [3]. The two consecutive quaternary centers embedded in the 1,6-diene 9 are worthy of note in the context of cyclopentene formation by RCM, and the five-membered ring compound 10 was obtained in high yield (97%) using catalyst [Ru]-I. The same type of strategy was applied for the efficient construction of the two vicinal quaternary carbon atoms present in the herbertanes sesquiterpenes (Scheme 1.2) [4]. 

An interesting feature of the A-aziridinylimine radical chemistry developed by Lee et al. is the unique ability of the precursor hydrazone carbon to serve as both radical acceptor and donor in a domino process. This is illustrated by the synthesis of a-cedrene in which two consecutive C—C bonds are formed generating a quaternary center in the sequence from 65 to 66 (Scheme 25.29). a-Cedrene, a major constituent of the sesquiterpene fraction of cedar-wood oil, is of great interest as perfumery material. 

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