**2.1. Molecular rearrangement of acetyl cedrene to cedrene follower**

The acetylation of cedrene **1** can lead to various products depending on the reaction conditions. Paknikar et al. [1] undertook a detailed study on the acetylation of cedar wood oil (Virginia) with acetic anhydride and polyphosphoric acid in dichloromethane which leads, besides acetyl cedrene **2**, also to a minor product, 1,7,7-trimethyl-2,3-(3′4'-dimethylbenzo) bicyclo[3.2.1]-octane **3**, called the follower. Structural analysis of **3** (**Scheme 1**) shows that rings A, B, C of **2** are rearranged as B, A, C in follower **3**.

One characteristic feature of the formation of the follower **3** is sluggish reaction rates. Density Functional Theory (DFT) calculation of B3LYP/6-31G\* type using the Gaussian version 09 (Gaussian) revealed that the first neutral intermediate **4** (**Scheme 2**) is higher in energy than acetyl cedrene by ~20 kcal. A series of further cascade- like cationic rearrangements is involved

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http://dx.doi.org/10.5772/intechopen.74998

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The formation of the neutral intermediate **4** is supported by the observation that this process is the reverse pathway for the biosynthesis of α-cedrene from FPP, which has been established previously [2]. Few other feasible mechanisms for the formation of follower **3** could be devised, and only the one presented fits the observation of 13C enriched label at the C-3′ position of follower **3**. Hence the key rearrangement is cyclopropylcarbinyl cation-cyclopropylcarbinyl cation rearrangement (CCR) [3, 4]. During the deuteriation of commercial acetyl cedrene, the follower was also deuterated, and it was observed that aromatic protons are exchanged. Interestingly, the product was only monodeuterated (**Scheme 1**) and the isotope was shared equally between the C-5′ and C-6′ positions of the follower **3**. This equal distribution of one deuterium atom between C-5′ and C-6′ can be accounted for by the facile

**2.2. Acid catalyzed rearrangement of moreliane based triketone. Characterization of** 

An interesting molecular rearrangement has been reported by Morales and co-workers [5]. They observed that triketone **5** on treatment with *p*-TSA in benzene resulted in the formation of a keto lactone **6**, a 1–11 seco-moreliane derivative and also the first representative of this

The rearrangement depicted in **Scheme 3** involves initial cyclobutane ring expansion of the protonated triketone, generation of carbocationic intermediate **7** which rearranges *via* transition state in to protonated seco-moreliane **8**. These steps are supported by DFT calculations.

with breaking and bond-forming intermediates.

**Scheme 2.** Mechanism for the formation of follower **3** from acetyl cedrene **2**.

1,2-hydride and 1,2-deuteride shifts and equilibration.

**keto lactone, a 1-11 seco-moreliane**

group (**Figure 1**).

**Scheme 1.** Acetyl cedrene **2** and its follower **3**. The numbering in the brackets is the one from acetyl cedrene.

Formation of **3** from **2** can only be explained by a multistep intramolecular rearrangement. This shows that: (i) ring C of 2 has undergone initial ring enlargement and subsequent ring contraction; (ii) cleavage of the C6–C7 bond of 2 and formation of the new C6-C2 bond; (iii) enlargement of ring A of **2** with concomitant loss of water. The mechanism for the formation of **3** from **2** when 1-13C labeled acetic anhydride was used is shown in **Scheme 2**.

Recent Developments in Selected Sesquiterpenes: Molecular Rearrangements, Biosynthesis… http://dx.doi.org/10.5772/intechopen.74998 89

**Scheme 2.** Mechanism for the formation of follower **3** from acetyl cedrene **2**.

particular reference to molecular rearrangements, biosynthesis and structural relationship among congeners. The coverage is not comprehensive but a focused review of the literature (2005–till September 2017) and only the relevant research articles having a link with the above

The acetylation of cedrene **1** can lead to various products depending on the reaction conditions. Paknikar et al. [1] undertook a detailed study on the acetylation of cedar wood oil (Virginia) with acetic anhydride and polyphosphoric acid in dichloromethane which leads, besides acetyl cedrene **2**, also to a minor product, 1,7,7-trimethyl-2,3-(3′4'-dimethylbenzo) bicyclo[3.2.1]-octane **3**, called the follower. Structural analysis of **3** (**Scheme 1**) shows that

Formation of **3** from **2** can only be explained by a multistep intramolecular rearrangement. This shows that: (i) ring C of 2 has undergone initial ring enlargement and subsequent ring contraction; (ii) cleavage of the C6–C7 bond of 2 and formation of the new C6-C2 bond; (iii) enlargement of ring A of **2** with concomitant loss of water. The mechanism for the formation

of **3** from **2** when 1-13C labeled acetic anhydride was used is shown in **Scheme 2**.

**Scheme 1.** Acetyl cedrene **2** and its follower **3**. The numbering in the brackets is the one from acetyl cedrene.

**2. Mechanisms of multistep molecular rearrangements, insight into biosynthesis and congeners for probing structure-biosynthetic** 

**2.1. Molecular rearrangement of acetyl cedrene to cedrene follower**

areas are selected for discussion.

88 Terpenes and Terpenoids

**relationship of selected natural products**

rings A, B, C of **2** are rearranged as B, A, C in follower **3**.

One characteristic feature of the formation of the follower **3** is sluggish reaction rates. Density Functional Theory (DFT) calculation of B3LYP/6-31G\* type using the Gaussian version 09 (Gaussian) revealed that the first neutral intermediate **4** (**Scheme 2**) is higher in energy than acetyl cedrene by ~20 kcal. A series of further cascade- like cationic rearrangements is involved with breaking and bond-forming intermediates.

The formation of the neutral intermediate **4** is supported by the observation that this process is the reverse pathway for the biosynthesis of α-cedrene from FPP, which has been established previously [2]. Few other feasible mechanisms for the formation of follower **3** could be devised, and only the one presented fits the observation of 13C enriched label at the C-3′ position of follower **3**. Hence the key rearrangement is cyclopropylcarbinyl cation-cyclopropylcarbinyl cation rearrangement (CCR) [3, 4]. During the deuteriation of commercial acetyl cedrene, the follower was also deuterated, and it was observed that aromatic protons are exchanged. Interestingly, the product was only monodeuterated (**Scheme 1**) and the isotope was shared equally between the C-5′ and C-6′ positions of the follower **3**. This equal distribution of one deuterium atom between C-5′ and C-6′ can be accounted for by the facile 1,2-hydride and 1,2-deuteride shifts and equilibration.
