DFT study of rearrangements in cyclopentylheptenyl carbocations

Abstract

Carbocation rearrangements relevant to sterol biosynthesis were investigated computationally by using the model cyclopentylheptenyl carbocations 1A and 1B. Five different rearrangement pathways of these equilibrating cations were located at the potential energy surface (PES), all calculated at the B3LYP/6-31G(d) level of theory. Each of these five distinct pathways differs from previous mechanistic proposals, and each involves new and unusual intermediates.

The carbocation continuum in terpene biosynthesis—where are the secondary cations?

“…biosynthesis have been described by the Hess, 23 Matsuda, 24 Vrcek, 25 and Gao 26 groups. To our knowledge, Hess was the first to describe quantum chemical calculations that support a biosynthetically relevant concerted combination of cyclization and shifting events that avoids a secondary carbocation minimum.…”

Formation of Beyerene, Kaurene, Trachylobane, and Atiserene Diterpenes by Rearrangements That Avoid Secondary Carbocations

“…In this mechanistic scheme, two secondary carbocation intermediates ( B and D , Scheme ) are invoked, ,, but whether or not these cations are actually viable intermediates is uncertain. Starting with the seminal work of Hess on steroid biosynthesis, several studies in which quantum chemical computations were employed to assess the inherent reactivity of other biologically relevant carbocations have shown that secondary carbocations can be avoided by combining two or more mechanistic steps into concerted processes that lead to tertiary carbocations. − In fact, it has been suggested that proposed secondary carbocations are more often transition state structures than minima, although secondary carbocations are predicted to be true minima in a few cases. ,, …”

Host‐Catalyzed Cyclodehydration–Rearrangement Cascade Reaction of Unsaturated Tertiary Alcohols

“…Similar to exocyclic cation 5, the initial hydride shift lowers the energy of the system by locating the positive charge within the ring, as indicated by DFT calculations. [18] Indeed, treatment of substrate 9 with hexamer I for 3 d yielded product 8 in 75% yield. Reaction monitoring via GC furthermore excludes substantial deprotonation, favoring a 1,2-hydride shift mechanism.…”

“…Subsequent 5-exo olefin cyclization results in cationic species 5, which is related to the protosterol cation observed in the biosynthesis of lanosterol. [17] Next, a 1,2-hydride shift generates the thermodynamically more stable [18] endocyclic cation 6. According to a detailed DFT study by Vrcek, the formation of intermediate 6 represents the rate determining step of the overall reaction cascade.…”

“…According to a detailed DFT study by Vrcek, the formation of intermediate 6 represents the rate determining step of the overall reaction cascade. [18] The spiro-type cation 6 then undergoes a WagnerMeerwein ring expansion to give intermediate 7, which eliminates to yield annulated cyclopentene 8 as the final product of the cyclorearrangement.…”