Mechanistic Hammett analysis

A recent DFT study has shown that retention of configuration observed for the above reactions is in agreement with the insertion of singlet nitrene and a concerted product formation [150 is the transition state for the reaction shown in Equation (6.135)]. Du Bois and coworkers have performed detailed mechanistic investigations of the intramolecular sulfamate ester C-H amination reaction catalyzed by a dirhodium complex. Reactivity patterns, Hammett analysis, and kinetic isotope effect studies have provided support for the concerted, asynchronous transition structure 151. A similar conclusion was arrived at for an analogous intermolecular process. ... 

Dirhodium tetracarboxylate complexes are among the most successful and well-studied catalysts for C-H amination. Early work by Miiller provided support for a concerted asynchronous reaction mechanism for intermolecular amination reactions using Rh2(OAc)4 and NsN=IPh [22-24]. Du Bois and coworkers have shown that carbamate and sulfamate esters can engage in oxidative cyclization reactions promoted by these same types of Rh complexes using PhI(OAc)2 as the terminal oxidant [93-96]. Mechanistic studies, which include Hammett analysis (p = 0.55... 

The results uncovered by Muller have been corroborated by the subsequent studies from the Du Bois group, particularly with respect to the intramolecular reaction. The stereospecific C(sp )—H insertion of the carbamate-derived nitrene depicted in Scheme 6A was the first relevant reaction in favor of the asynchronous concerted addition.More significantly, the extensive analysis of the rhodium-catalyzed intramolecular C(sp )-H amination of sulfamates has led to the same conclusion. The Hammett analysis (/0= —0.55 vs. and the kinetic isotope effect observed from the monodeuterated phenylpropyl sulfamate 9 (KIE = 2.6 0.2) clearly argue in favor of this mechanistic scenario (Scheme 17). Additionally, the reaction from the cyclopropyl radical clock 12 supports this hypothesis by furnishing a single product isolated with an excellent yield of 91%. 

Not every excess acidity mechanistic analysis has been an outstanding success. For instance, several enolization studies have used this technique. The enolization of acetophenone was one of the reactions originally studied by Zucker and Hammett 146 their sulfuric acid rate constant data, obtained by iodine scavenging (the reaction is zero-order in halogen), was used in an excess acidity analysis,242 together with additional results obtained for some substituted acetophenones (using bromine scavenging).243... 

O Shea, K. and Cardona, C., Hammett study on the Ti02-catalyzed photooxidation of para-substituted phenols a kinetic and mechanistic analysis, /. Org. Chem., 59, 5005, 1994. 

The various multiparameter equations can usually improve the correlation of data that give poor correlations with the single-parameter Hammett equation. It must be recognized that this in part may be a direct consequence of the introduction of additional variable parameters. To derive solid mechanistic insight into the basis of improved correlation requires a critical appraisal of the results, and statistical analysis may be necessary. The details of critical statistical evaluation of free-energy... 

In a report describing acid-promoted Ritter reactions involving a-methylene-)5-hydroxyesters, an I -type process was found to be the preferred mechanism. For compound (104), both Ritter reaction products (105 and 106) are obtained. In order to rule out 5 2 or Sf 2 mechanisms, kinetic analysis was performed, kinetic isotope effects were evaluated, and both Hammett and Eyring plots were done. The mechanistic studies were consistent with an I -type process being preferred with initial formation of the oxonium cation, loss of water, and formation of the allylic acarbocation (107). DFT calculations indicated nucleophilic attack at the terminal carbon (107b, 5 10 was favored by about 2.6kcalmol over attack at the benzylic position (107a, 5 1) (Scheme 23). 

There has been a mechanistic investigation of the possible intermediates in the thermal C -C cyclization of enyne-carbodiimides [424]. Kinetic studies of enyne-carbodiimides with electron-withdrawing substituents gave a nonlinear Hammett correlation. This supported a concerted/nonpolar mechanism to produce a carbene intermediate. However, when electron-donating substituents were present, the results indicated a polar cyclization mechanism giving a carbene with zwitte-rionic character. Earlier, theoretical investigations by density functional theory (DFT) and NBO analysis had supported a diradical intermediate. 

---