Mechanistic insights on C(acyl)-N functionalisation mediated by late transition metals.

The carboxamide functional group has a privileged role in organic and biological chemistry due to its prevalence and utility across synthetic and natural products. Due to nN → π*CO delocalisation, amides and related functional groups are typically kinetically resistant to degradation. Nonetheless, over the past decade, transition metal catalysis has transformed our ability to utilise molecules featuring C(acyl)-N units as reactants. Alongside the burgeoning catalytic applications ranging from COx utilisation to small molecule synthesis, elucidation of the underlying mechanisms remains a critical ongoing effort. Herein, we aggregate and analyse current understanding of the mechanisms for C(acyl)-N functionalisation of amides and related functional groups with a focus on recent developments involving mechanisms unique to the late transition metals. Discussion is organized around three general mechanistic manifolds: redox-neutral mechanisms, 2e- redox-cycling mechanisms, and mechanisms involving 1e- redox steps. For each class, we focus on reactions that directly involve a transition metal mediator/catalyst in the C(acyl)-N cleavage step. We conclude with an outlook on the outstanding ambiguities and opportunities for innovation.

Comparative Study of 0.5% Bupivacaine, 0.5% Ropivacaine, and 0.75% Ropivacaine With Fentanyl as a Continuous Intraoperative Epidural Infusion on Post-operative Analgesia.

Introduction Persistent postoperative pain leads to impaired patient recovery and delays in discharge of patients. The aim was to compare the efficacy of 0.5% bupivacaine to two varying concentrations of ropivacaine, specifically 0.5% and 0.75%, along with fentanyl as a continuous epidural infusion in providing adequate pain relief for patients subjected to infraumbilical surgeries. Materials and methods A prospective randomized comparative study was carried out on 150 patients and was divided into three groups, namely group B, group R, and group RP. Group B indicates (0.5% bupivacaine), group R means (0.5% ropivacaine), and finally, group RP means (0.75% ropivacaine); the three groups had 50 patients each. Group B was administered an epidural infusion of bupivacaine at a concentration of 0.5%, group R was given 0.5% ropivacaine, and group RP was treated with 0.75% ropivacaine; all three groups included 40 mcg fentanyl. The duration of the motor and sensory blockade and the time needed for the first rescue analgesia after the stoppage of epidural infusion were assessed in all three groups. The data were statistically analyzed using the ANOVA, "post hoc Tukey," and chi-square tests. Results Comparison of the duration of motor and sensory blockade among all three groups showed that group RP (0.75% ropivacaine with 2 mcg/cc fentanyl) had the longest duration of 328.8 and 406 minutes, and the difference was statistically significant (p < 0.001). Comparison of the time of stoppage of epidural infusion to the requirement of first rescue analgesia showed that the group that received 0.75% ropivacaine with 40 mcg fentanyl had the highest value of 258.6 minutes and was statistically significant (p < 0.001). Conclusion Epidural intraoperative infusion of 0.75% ropivacaine with fentanyl offers better postoperative pain relief as compared to both 0.5% bupivacaine and 0.5% ropivacaine with fentanyl.

Distinguishing Competing Mechanistic Manifolds for C(acyl)-N Functionalization by a Ni/N-Heterocyclic Carbene Catalyst System.

Carboxylic acid derivatives are appealing alternatives to organohalides as cross-coupling electrophiles for fine chemical synthesis due to their prevalence in biomass and bioactive small molecules as well as their ease of preparation and handling. Within this family, carboxamides comprise a versatile electrophile class for nickel-catalyzed coupling with carbon and heteroatom nucleophiles. However, even state-of-the-art C(acyl)-N functionalization and cross-coupling reactions typically require high catalyst loadings and specific substitution patterns. These challenges have proven difficult to overcome, in large part due to limited experimental mechanistic insight. In this work, we describe a detailed mechanistic case study of acylative coupling reactions catalyzed by the commonly employed Ni/SIPr catalyst system (SIPr = 1,3-bis(2,6-di-isopropylphenyl)-4,5-dihydroimidazol-2-ylidine). Stoichiometric organometallic studies, in situ spectroscopic measurements, and crossover experiments demonstrate the accessibility of Ni(0), Ni(I), and Ni(II) resting states. Although in situ precatalyst activation limits reaction efficiency, the low concentrations of active, SIPr-supported Ni(0) select for electrophile-first (closed-shell) over competing nucleophile-first (open-shell) mechanistic manifolds. We anticipate that the experimental insights into the nature and controlling features of these distinct pathways will accelerate rational improvements to cross-coupling methodologies involving pervasive carboxamide substrate motifs.