Computer-Assisted Mechanistic Evaluation of Organic Reactions. 24. Carbene Chemistry

Iron(III) Corroles and Porphyrins as Superior Catalysts for the Reactions of Diazoacetates with Nitrogen‐ or Sulfur‐Containing Nucleophilic Substrates: Synthetic Uses and Mechanistic Insights

“…[15] There have also been several mechanistic investigations into O À H insertion reactions in which both concerted and stepwise pathways were considered. [2,16] A Hammett plot analysis led Wang and co-workers to conclude the reaction proceeded through a concerted transition state, [17] whereas Hu and co-workers found very strong evidence in favor of a stepwise reaction pathway. [18] Aldehydes and imines were used as electrophilic trapping agents of the proposed reaction intermediate, an oxonium ylide formed by the nucleophilic addition of the alcohol to the metal-carbene.…”

A Rh(II)-catalyzed multicomponent reaction by trapping an α-amino enol intermediate in a traditional two-component reaction pathway

“…2 . First, we were interested in how to generate α-amino enol D. It is well known that Rh(II)-associated carbenes readily react with water/alcohol to form the corresponding active oxonium ylides, which can yield O–H insertion products through a proton transfer process ( 74 – 76 ). Xia et al .…”

“…To further understand the two competitively crucial transformation pathways of a-amino enol D into ketone 7 by keto-enol tautomerization versus trapping by vinylimine intermediate E into product 6, we performed detailed DFT calculations for the transformation of the two key intermediates, for example, a-amino enol D and vinylimine ion E. The typically calculated free energy profiles for the formation and the elementary transformations of a-amino enol D are shown in Fig.2. First, we were interested in how to generate a-amino enol D. It is well known that Rh(II)-associated carbenes readily react with water/ alcohol to form the corresponding active oxonium ylides, which can yield O-H insertion products through a proton transfer process(74)(75)(76).Xia et al (77) also demonstrated this process by theoretical calculations. Our group further demonstrated that these oxonium ylides could be trapped by electrophiles during the experiments before the proton transfer took place(78,79).…”

Design Constraints in Practical Syntheses of Complex Molecules: Current Status, Case Studies with Carbohydrates and Alkaloids, and Future Perspectives

“…94 The concept of synthons 43 and network analysis 95 proposed by Corey ultimately led to computer-assisted design (CAD). [96][97][98][99][100][101][102][103][104][105][106] Connectivity analysis as an exhaustive tool in design has been described by Wender; 2 Bertz has successfully coupled it with graph theory 5 to predict and explain the issues of complexity, reflexivity (or symmetry), 5,107 and vulnerability 5 in terms that may seem somewhat esoteric for the average organic chemist.…”

“…The spectrum of attempts ranges from the application of graph theory and set topology, as done for example by Ugi, 111 Bertz, 5 and others, 6 on one hand, to the relatively simple connectivity analysis by Corey, 108,112 Wender, 2 Hendrickson, 101 and Hanessian 98,100 on the other. In the middle of the spectrum lie Jorgensen's CAMEO programs, 104,105 which aid in the analysis of actual mechanistic pathways, and some of the databases and planning programs advanced by Hanessian. 100 The former group of applications is not readily accessible to the usually impatient synthetic chemist who is either unwilling or unable to make the time investment required to learn these special techniques.…”