Mechanistic with carbamates

A mechanistic analysis of antibody DF8-D5 showed it to cleave p-nitrophenyl carbamate [134] with kcat = 0.3 s l, Km = 120 p,M, and cat/ uncat = 300 at 14°C (Appendix entry 4.3) (Wentworth et al., 1997). This is some tenfold more active than a carbamatase antibody generated by Schultz... 

It should be realized that with the exception of a few groups of chemicals (such as some organophosphorous and carbamate pesticides as well as some polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs), precise mechanistic information on their toxic effects are scarce. In realizing that the exact molecular mechanism is not known for most chemicals the term mode of action is used to describe toxicides that appear to be similar albeit the mechanism is not known in detail, see also Section 4.2.6. For several groups of endocrine disrupters this terminology seems appropriate. 

Advantageously, in the context of subsequent synthetic manipulation, the acylated products in these processes are carbamates (rather than amides). Fu proposed a mechanistic pathway that involves rapid initial reaction of the catalyst with the 0-carbonyloxyazlactone to form an ion pair, followed by slow transfer of the methoxycarbonyl group from this ion-pair to the amine in the enantioselectivity determining step (Fig. 6) [99]. 

Several lines of inquiry have been explored to address key mechanistic issues in the rhodium-catalyzed C-H insertion of carbamates and sulfamates (Scheme 17.32) [99]. A pathway involving initial condensation between substrate 96 and PhI(OAc)2 to form iminoiodinane 97 was envisioned in the original design of this chemistry. Coordination of 97 to an axial site on the rhodium dimer would promote nitrene formation and the ensuing C-H insertion event Surprisingly, control experiments with PhI(OAc)2 and sulfamate 96 (or analogous carbamates) give no indication for a reaction between these two components. 

The preparation of carbonates is mechanistically closely related to the synthesis of carbamates, and similar reagents can be used for this purpose (Table 14.10). Resin-bound alcohols can be directly converted into carbonates by treatment with a chloro-formate (see Experimental Procedure 14.2), in two steps by activation with phosgene or a synthetic equivalent thereof followed by reaction with an alcohol in the presence of a base, or by treatment of a resin-bound alcohol with carbon dioxide and an alkyl halide under basic reaction conditions [125]. Thiocarbonates can be prepared from... 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

An impressive range of nucleophiles was successful for arylboronic acids in the presence of Cu(OAc)2 and base, which included amine, anilines, amides, imines, ureas, carbamates, sulfonamides, and aromatic heterocycles (e.g., imidazoles, pyrazoles, triazoles, tetrazoles, benzimidazoles, and indazoles) (Equation (226)) 996 997 1000-1011 For all the reactions investigated with A-nucleophiles, the use of Et3N resulted in yields superior to those obtained with pyridine, but pyridine was the base of choice for the preparation of imidazole derivatives from heteroarenes. For the tetrazole, NMO and DBU were studied as alternative bases. There are mechanistic studies.999,1002-1013... 

Mechanistic studies on the interaction of quinine or quininyl-9-O-carbamates 69 and 70 with selected enantiomer pairs, employing sophisticated NMR experiments and molecular modeling, have been carried out by the Salvadori group. These studies revealed that due to the multifunctional character of the CSA molecules and their specific conformational preferences, each type of analyte induced its own specific interaction pattern [134, 137]. The main driving forces leading to enantiodiscrimination are due to hydrogen bonds between hydroxy group in QN or... 

While the majority of Rh-catalyzed C-H amination processes employ hyperva-lent iodine oxidants and sulfonamide derivatives, Lebel and coworkers have demonstrated that /V-tosyloxycarbamates will engage with catalytic Rh2(02CCPh3)4 and K2CC>3 to afford products of intramolecular C-H insertion (Fig. 22) [104, 5, 105]. Similar to Du Bois earlier work involving oxidative cyclization with 1 ° carbamates [94], the /V-tosyloxy derivatives display a strong bias for oxazolidinone formation. Selectivity trends and other mechanistic data support a reaction pathway involving a Rh-nitrene oxidant. Intermolecular amination of simple benzylic substrates... 

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