A new protocol for the aromatization of tetrahydrocarbazoles has been achieved using a catalytic amount of iodine, giving high yields. The role of iodine in the aromatization has been explained by DFT, and its wide scope is extended to the total synthesis of glycozoline and murrayafoline A. This method has proven to be tolerant of a broad range of functional groups.

For catalytic asymmetric hydroformylation (AHF) of alkenes to chiral aldehydes, though a topic of high interest, the contemporary developments remain largely empirical owing to rather limited molecular insights on the origin of enantioselectivity. Given this gap, herein, we present the mechanistic details of Rh-(S,S)-YanPhoscatalyzed AHF of α-methylstyrene, as obtained through a comprehensive DFT (ω-B97XD and M06) study. The challenges with the double axially chiral YanPhos, bearing an N-benzyl BINOL-phosphoramidite and a BINAP-bis(3,5-t-Bu-aryl)phosphine, are addressed through exhaustive conformational sampling. The C−H•••π, π•••π, and lone pair•••π noncovalent interactions (NCIs) between the N-benzyl and the rest of the chiral ligand limit the N-benzyl conformers. Similarly, the C−H•••π and π•••π NCIs between the chiral catalyst and α-methylstyrene render the siface binding to the Rh-center more preferred over the re-face. The transition state (TS) for the regiocontrolling migratory insertion, triggered by the Rh-hydride addition to the alkene, to the more substituted α-carbon is 3.6 kcal/mol lower than that to the β-carbon, thus favoring the linear chiral aldehyde over the achiral branched alternative. In the linear pathway, the TS for the hydride addition to the si-face is 1.5 kcal/mol lower than that to the re-face, with a predicted ee of 85% for the S aldehyde (expt. 87%). The energetic span analysis reveals the reductive elimination as the turnover determining step for the preferred S linear aldehyde. These molecular insights could become valuable for exploiting AHF reactions for substituted alkenes and for eventual industrial implementation.

Pincer-based ( R2 POCN R ′ 2 )PdCl complexes along with CuI cocatalyst catalyze the arylation of azoles with aryl iodides to give the 2-arylated azole products. Herein, we report an extensive mechanistic investigation for the direct arylation of azoles involving a well-defined and highly efficient ( iPr2 POCN Et2 )PdCl (2a) catalyst, which emphasizes a rare Pd II −Pd IV −Pd II redox catalytic pathway. Kinetic studies and deuterium labeling experiments indicate that the C−H bond cleavage on azoles occurs via two distinct routes in a reversible manner. Controlled reactivity of the catalyst 2a underlines the iodo derivative ( iPr2 POCN Et2 )PdI (3a) to be the resting state of the catalyst. The intermediate species ( iPr2 POCN Et2 )Pd-benzothiazolyl (4a) has been isolated and structurally characterized. A determination of reaction rates of compound 4a with electronically different aryl iodides has revealed the kinetic significance of the oxidative addition of the C(sp 2 )−X electrophile, aryl iodide, to complex 4a. Furthermore, the reactivity behavior of 4a suggests that the arylation of benzothiazole proceeds via an oxidative addition/ reductive elimination pathway involving a ( iPr2 POCN Et2 )Pd IV (benzothiazolyl)(Ar)I species, which is strongly supported by DFT calculations.

Concise and protecting-group free synthesis of ent-palmyrolide A and (-)-cis-palmyrolide A were achieved starting from commercially available (S)-citronellal. The key fragment of palmyrolide A, "(5S,7S)-7-hydroxy-5,8,8-trimethylnonanamide", which makes up the most challenging part of the target molecule, was prepared in just three steps. A plausible mechanism for the trans-cis isomerization of the double bond in the macrocycle has been investigated.

Investigations on the factors that govern unusual branched alkylation of 2-aroylbenzofurans with acrylates by Ru-catalyzed carbonyl-directed C-H activation has been carried out by calculating the kinetics associated with the two key steps-the coordination of the acrylate with the intermediate ruthenacycle and the subsequent migratory insertion reaction-studied with the help of DFT calculations. Eight possible orientations for each mode of alkylation have been considered for the calculations. From these calculations, it has been understood that there is a synergistic operation of the steric and electronic effects favoring the branched alkylation. Further DFT investigations on the alkylation of the isomeric 3-aroylbenzofurans indicated a preference for the linear alkylation and this has been verified experimentally. Overall, the observed/calculated complementary selectivity in the alkylation of 2-/3-aroylbenzofurans with acrylates reveals that the substrate-dependent charge distribution of the Ru-C bond in the intermediate ruthenacycle is an important determining factor and thus the current work opens up a new domain of substrate design for controlling regioselectivity.