Mechanism of Samarium-Catalyzed 1,5-Regioselective Azide–Alkyne [3 + 2]-Cycloaddition: A Quantum Mechanical Investigation

The mechanism of the samarium-catalyzed 1,5-regioselective azide–alkyne [3 + 2]-cycloaddition (SmAAC) reaction has been examined with quantum mechanical calculations at the B3LYP/6-31+G­(d,p) level of theory with ECP51MWB on Sm. Four stepwise pathways were located, with two leading to the 5-endocyclic 1,5-disubstituted 1,2,3-triazole product <b>PSmL₂</b> (paths 1 and 2) and the other two to the exocyclic product <b>ExoPSmCl₂</b> (path 3) as well as 1,4-disubstituted 1,2,3-triazole <b>RegPSmL</b>_<b>2</b> (path 4), respectively. Among them, path 2 (<b>R-COM1</b>–<b>TS12</b>–<b>COM2</b>–<b>TS23</b>–<b>COM3</b>–<b>TS3P</b>–<b>PSmL₂</b>) is the most favored one both in the gas phase and in toluene solution, which is in good agreement with the experimental data. Moreover, 1,1-insertion forming <b>COM2</b> in path 2 is the rate-determining step. The computational results also infer that the participation of samarium catalyst changes the distribution of the electrostatic potential on the reactants’ surface, which determines the polarization direction of the reactants and formation of different intermediates (<b>COM1</b> and <b>RegCOM1</b>), and finally affects the regioselectivity. When solvent corrections for toluene are considered, the 1,1-insertion process is discouraged, while the intramolecular [1,3]-shift reaction is facilitated

Imino-N-Heterocyclic Carbene Palladium(II) Complex-Catalyzed Direct Arylation of Electron-Deficient Fluoroarenes with “On and Off” Chelating Effect Assistance

An imino-N-heterocyclic carbene palladium­(II) complex with a bulky substituted group on the imino nitrogen was used to catalyze the direct arylation of electron-deficient fluoroarenes with aryl halides. A series of electron-poor substrates and aryl bromides could be coupled in good to excellent yields with satisfactory position selectivity (20 examples, up to 93%). These arylations could proceed at a relatively low temperature (80 °C, 20 examples, up to 95%) with mono-N-protected amino acid assistance. Some of them even gained higher yields than those at high temperature (110 °C). Otherwise, some aryl iodides can forge cross-coupling products in yields of nearly 30% under the optimized conditions. The rate profiles for arylation of electron-poor arenes were measured in the presence of the imino-N-heterocyclic carbene palladium­(II) complex or Pd­(OAc)₂ as the catalyst, which showed that the former could keep catalytic activity for a longer time. Computational studies indicated that the imino nitrogen in the imino-N-heterocyclic carbene ligand can detach from and attach to the central metal in the catalytic cycle. Thus, the coordination site could be protected, and this effect may be responsible for decreasing the rate of palladium black formation

Primary treatment and response in patients with extranodal natural killer (NK)/T-cell lymphoma.

<p>Abbreviations: CRP: C-reactive protein; CT: chemotherapy; RT: radiotherapy; CHOP: cyclophosphamide+doxorubicin+vincristine+prednisone; EPOCH: etoposide+doxorubicin+vincristine+cyclophosphamide+prednisone; ATT: alternating triple therapy (CHOP-B, cyclophosphamide+doxorubicin+vincristine+bleomycin+prednisone; IMVP-16, ifosfamide+methotrexate+etoposide; DHAP, dexamethasone+cisplatin+cytarabine); GEMOX+L-asp: gemcitabine+oxaliplatin+L-asparaginase; SMILE: dexamethasone+methotrexate+ifosfamide+L-asparaginase+etoposide.</p

Univariate and multivariate analysis of prognostic factors for PFS and OS in patients with ENKTL.

<p>Abbreviations: PFS: progression-free survival; OS: overall survival; LN: lymph node; ENKTL: extranodal NK/T-cell lymphoma; RR: relative risk; CI: confidence interval; EUNKTL: extra-upper aerodigestive tract NK/T-cell lymphoma; LDH: lactate dehydrogenase; CRP: C-reactive protein; IPI: International Prognostic Index; KPI: Korean Prognostic Index; ALC: absolute lymphocyte count.</p

Survival outcome of patients based on the C-reactive protein (CRP) level.

<p>(A) Progression-free survival (PFS) of patients according to baseline CRP level (≤10 mg/L vs. >10 mg/L). (B) Overall survival (OS) of patients according to baseline CRP level (≤10 mg/L vs. >10 mg/L).</p

Survival outcome of patients according to the Korean Prognostic Index (KPI) score.

<p>(A) Overall survival (OS) according to the KPI for patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type. (B) OS of patients with KPI score = 0–1 according to the new prognostic index. (C) OS of patients with KPI score = 1–2 according to the new prognostic index. (D) OS of patients with KPI score = 2–4 according to the new prognostic index.</p

Survival outcome of patients according to the novel prognostic model.

<p>(A) Overall survival (OS) according to the new prognostic index for patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type. (B) OS of patients with low International Prognostic Index risk (IPI score = 0–1) according to the new prognostic index.</p

Overall survival and relative risk of death according to risk group as defined by the new prognostic index.

a<p>Factors: age >60 years, LDH >245 U/l, CRP>10 mg/L, and albumin <35 g/L.</p><p>Abbreviations: OS: overall survival; RR: relative risk; CI: confidence interval; N/A: not applicable.</p

The pros and cons of the IPI, KPI and current prognostic model.

<p>Abbreviations: IPI: International Prognostic Index; KPI: Korean Prognostic Index; LDH: lactate dehydrogenase; ECOG PS: Eastern Cooperative Oncology Group performance status; LN: lymph nodes; CRP: C-reactive protein.</p

Baseline characteristics of patients by serum CRP level.

a<p>Data of EBV-DNA copy number were available for 81 patients and the median value was 5,050 copies/ml.</p><p>Abbreviations: CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; LDH: lactate dehydrogenase; LN: lymph node; EBV-DNA: Epstein–Barr virus-DNA; UNKTL: upper aerodigestive tract NK/T-cell lymphoma; EUNKTL: extra-upper aerodigestive tract NK/T-cell lymphoma; IPI: International Prognostic Index; KPI: Korean Prognostic Index.</p