Triggering the Directional Selectivity of a Ring‐Closure Reaction Leads to Pyridoazacarbazoles with Anticancer Properties

We herein describe a facile and versatile synthetic route to the tetracyclic system of 6‐substituted 5,6‐dihydro‐11H‐pyrido[3,2‐i]‐1‐azacarbazoles with promising anticancer properties. These derivatives are built up by an elegant one‐step base‐catalyzed synthetic procedure from commercially available building blocks. One additional step provides the corresponding skeleton hitherto unknown in the literature. The possibility to synthesize a large library of compounds with various substitution patterns utilizing this method underlines the importance of this synthetic procedure.     

Palladium‐Catalyzed Domino CH/NH Functionalization: An Efficient Approach to Nitrogen‐Bridged Heteroacenes

Palladium‐catalyzed domino C?H/N?H functionalization for the synthesis of novel nitrogen‐bridged thienoacenes and 10H‐benzo[4,5]thieno[3,2‐b]indole derivatives from dihaloarene is reported. This domino sequence consists of initial C?H functionalization of the benzo[b]thiophene moiety, followed by Buchwald–Hartwig coupling. This transformation is also useful for the synthesis of highly π‐extended compounds.     

An easy-to-use estimate of the energy-release rate for crack arrays

Formation of crack arrays plays an increasing role in several fields of applied physics. The energy-release rate of the cracks controls the development of the array. Therefore, following the concept of configurational forces, a simplified analytical expression is provided for the energy-release rate, which is based both on numerical studies and on a specially adapted beam model. Comparisons of this easy-to-use estimate of the energy-release rate with established results from the literature as well as detailed numerical results are presented. The provided estimate of the energy-release rate can easily be extended to non-equidistant cracks and an anisotropic material.     

New mechanistic insights into the Claisen rearrangement of chorismate – a Unified Reaction Valley Approach study

ABSTRACT

The Bacillus subtilis chorismate mutase catalysed Claisen rearrangement of chorismate to prephenate is one of the few pericyclic processes in biology, and as such provides a rare opportunity for understanding how Nature promotes such rearrangements so successfully. The major focus of this work is on (i) Exploring the hypothesis that the mechanism of the chorismate rearrangement is the same in the gas phase, in the aqueous solution and in the enzyme; (ii) Investigating current suggestions that the enzyme lowers the barrier via transition state stabilisation rather than via space confinement; and (iii) A comparison of Nature's way of catalysing the reaction with a gold(I) catalysed chorismate rearrangement. Based the Unified Reaction Valley Approach (URVA), for the first time, a detailed one-to-one comparison of the rearrangement in the gas phase, in the aqueous solution and in the enzyme is presented. URVA confirms that the actual chemical process of CO bond breaking and CC bond forming is the same for all media and unravels the unique catalytic function of the enzyme as a combination of shortening the process of positioning the enolpyruvyl side chain over the cyclohexadienyl ring by space confinement in concert with facilitating CO cleavage by enhanced charge polarisation. The transition state does not play a signifiant role for the rearrangement. In contrast, the gold catalyst changes the chemical process. The rearrangement is split into two steps by switching between Au[I]-π and Au[I]-σ complexation, thus avoiding the energy consuming CO breakage in the first step. Suggestions are made for metalloenzyme analogues combining both strategies.