Carbonyl mode acids

When considering factors that may influence the reactivity and conformation of carbonyl-Lewis acid complexes, primary attention should be given to the modes of coordination of Lewis acids to carbonyl groups, analyzing the exact location of the Lewis acid with respect to its carbonyl ligand. There are several different possible modes of coordination. First, purely electrostatic interaction can be considered, in which the metal is situated at the negative end of the C=0 dipole [C-0-M= 180°... 

Rates of addition to carbonyls (or expulsion to regenerate a carbonyl) can be estimated by appropriate forms of Marcus Theory. " These reactions are often subject to general acid/base catalysis, so that it is commonly necessary to use Multidimensional Marcus Theory (MMT) - to allow for the variable importance of different proton transfer modes. This approach treats a concerted reaction as the result of several orthogonal processes, each of which has its own reaction coordinate and its own intrinsic barrier independent of the other coordinates. If an intrinsic barrier for the simple addition process is available then this is a satisfactory procedure. Intrinsic barriers are generally insensitive to the reactivity of the species, although for very reactive carbonyl compounds one finds that the intrinsic barrier becomes variable. ... 

Rhodium catalyzed carbonylations of olefins and methanol can be operated in the absence of an alkyl iodide or hydrogen iodide if the carbonylation is operated in the presence of iodide-based ionic liquids. In this chapter, we will describe the historical development of these non-alkyl halide containing processes beginning with the carbonylation of ethylene to propionic acid in which the omission of alkyl hahde led to an improvement in the selectivity. We will further describe extension of the nonalkyl halide based carbonylation to the carbonylation of MeOH (producing acetic acid) in both a batch and continuous mode of operation. In the continuous mode, the best ionic liquids for carbonylation of MeOH were based on pyridinium and polyalkylated pyridinium iodide derivatives. Removing the highly toxic alkyl halide represents safer, potentially lower cost, process with less complex product purification. 

Most workers try to explain the final stereochemistry of the OH group on the basis of adsorption. That is, the mode of adsorption determines the resulting stereochemistry, assuming that the addition of hydrogen occurs cis from the surface up to the bottom of the adsorbed carbonyl group. Most investigators seem to assume that the carbonyl is protonated in acidic media and the mode of adsorption of this species is different from the unprotonated species (in neutral and basic media). 

Recent mechanistic studies using HP infrared equipment, as well as HP-NMR measurements involving the use of CO and CH3I, have allowed the iridium intermediates which are present in solution as methyl acetate and water, and are consumed to produce acetic acid [.12, 34, 41-43], to be followed. All of these observations can be rationalized by a single catalytic cycle (see Figure 8.5), in which equilibria exist between the neutral and anionic complexes for all species. The main species involved in the carbonylation, which are detected in batch mode under carbonylation conditions [34], and correspond to the slower steps of catalysis, are the methyl—iridium and acetyl-iridium complexes [Ir(CH3)l3(CO)2] and [Ir(COCH3)l3(CO)2] respectively. 

The lactone concept is not restricted to the simple model biaryl synthesis presented here. It has been successfully expanded to a broad series of structurally diverse biaryl substrates (e.g., lactones with additional stereocenters and functional groups, configurationally stable lactones, seven-membered lactones, and again configurationally unstable biaryl hydroxy aldehydes ), to different activation modes in the ring-opening step (e.g., use of metallated nucleophiles, carbonyl activation by Lewis acids, (Ti -complexation, etc.), and for various strategies of stereoselection (e.g., external vs. internal asymmetric induction). ... 

Hydrogen bonding to substrates such as carbonyl compounds, imines, etc., results in electrophilic activation toward nucleophilic attack (Scheme 3.1). Thus, hydrogen bonding represents a third mode of electrophihc activation, besides substrate coordination to, for example, a metal-based Lewis acid or iminium ion formation (Scheme 3.1). Typical hydrogen bond donors such as (thio)ureas are therefore often referred to as pseudo-Lewis-acids. ... 

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