Caryolene-forming carbocation rearrangements

Abstract

SummaryDensity functional theory calculations on mechanisms of the formation of caryolene, a putative biosynthetic precursor to caryol-1(11)-en-10-ol, reveal two mechanisms for caryolene formation: one involves a base-catalyzed deprotonation/reprotonation sequence and tertiary carbocation minimum, whereas the other (with a higher energy barrier) involves intramolecular proton transfer and the generation of a secondary carbocation minimum and a hydrogen-bridged minimum. Both mechanisms are predicted to involve concerted suprafacial/suprafacial [2 + 2] cycloadditions, whose asynchronicity allows them to avoid the constraints of orbital symmetry.

Do Anti‐Bredt Natural Products Exist? Olefin Strain Energy as a Predictor of Isolability

“…While OS energy therefore appears to be au seful and simple diagnostic tool, the behavior of aNPdepends not only on its thermodynamic stability but also on its kinetic stability under the conditions used for extraction, isolation, and storage.T hree NPs that contain reactive bridgehead double bonds are known:c erorubenic acid-I (25), [25] FR182877 (26), [26,27] and sesquiterpene 27 [28,29] (Figure 4). Both 25 and 26 undergo slow aerial oxidation to give epoxides (e.g.…”

The catalytic effect of the NH3 base on the chemical events in the caryolene‐forming carbocation cascade

“…This reaction step is very similar to a 2‐step mechanism, but does not involve a discrete intermediate on the PES. In fact, decoupling the two bond‐forming events allows the constraints expected on orbital‐symmetry grounds to be avoided . Five reaction regions along ξ can be identified and six reaction works: reactant region (R; ), where the reactants are prepared through structural rearrangements in order to activate the process; transition state region (TS; before and after the transition state, respectively), where the primary transition to distorted products occurs; intermediate region (I; ), a hybrid region, where certain structural and electronic rearrangements occur although no PES intermediate is actually formed; quasi‐transition state region (QTS; ), which drives the final transition to products; product region (P; ), where the distorted products relax structurally to their final equilibrium state.…”

“…Terpenes/terpenoids comprise the largest class of natural products, with more than 60,000 known compounds . These molecules contain complex carbon skeletons derived from acyclic precursors via (poly)cyclization/rearrangement reactions involving carbocations as intermediates (e.g., caryolene formation, Scheme ) . A full understanding of the properties of carbocations has been hampered by their very short lifetimes .…”

“…In a previous study, Nguyen and Tantillo proposed two mechanistic models for caryolene formation (Scheme ). The first step of the mechanism, A → B , was predicted to be the same for both base‐free and base‐promoted reaction.…”

Feasibility of Intramolecular Proton Transfers in Terpene Biosynthesis – Guiding Principles

“…A recent theoretical study on caryolene formation ( Figure 1a) described a 1,6-proton-transfer process. 22 This process (proton transfer from C15 to C7) is predicted to have a barrier of >20 kcal/mol (Table 1), which is much larger than the barriers predicted for 1,6-proton transfers involved in italicene and miltiradiene (vide inf ra) formation. However, an alternative deprotonation/reprotonation pathway was predicted to have a much lower barrier.…”