Sterically demanding carbonyl compounds

As emphasized above, the practical utility of organocerium compounds is to circumvent the problems which are faced with the corresponding Grignard and organolithium reagents because of their inability to react effectively with sterically demanding carbonyl compounds and carbon-heteroatom unsaturated bonds which have acidic a-protons. Some of the latest examples are shown below. 

As can be seen from Table 1, a whole set of compounds is available from the reaction of Eq. (5), which shows the high variability of both the substituents at silicon and the introduced metal. This method is only limited by the steric demand of the substituents. If the residues at the silicon are too bulky, no reaction according to Eq. (5) occurs. The method also allows the use of dinuclear carbonylate anions... 

Development of new reduction systems that reduce sterically hindered compounds The reported examples of reduction of carbonyl compounds are usually for the substrates that can be easily reduced such as methyl ketones. Since the demand for reduction of various types of compounds is increasing, investigation of new biocatalytic reductions is required. Photosynthetic organisms are not investigated yet, and they may have new type of enzymes, which can reduce sterically hindered compounds. 

The stereoselectivity of the Wittig reaction is believed to be the result of steric effects that develop as the ylide and carbonyl compound approach one another. The three phenyl substituents on phosphorus impose large steric demands that govern the formation of the diastereomeric adducts.240 Reactions of unstabilized phosphoranes are believed to proceed through an early TS, and steric factors usually make these reactions selective for the d.v-alkcnc.241 Ultimately, however, the precise stereoselectivity is dependent on a number of variables, including reactant structure, the base used for ylide formation, the presence of other ions, solvent, and temperature.242... 

So far as steric effects are concerned, the least energy-demanding direction of approach by the nucleophile to the carbonyl carbon atom will be from above, or below, the substantially planar carbonyl compound. It is also likely to be from slightly to the rear of the carbon atom (cf. 12), because of potential coulombic repulsion between the approaching nucleophile and the high electron density at the carbonyl oxygen atom ... 

A class of ligands which is very flexible in terms of its denticity, donor atom geometry, and steric demands are Schiff bases derived from salicyladehyde or related carbonyl compounds carrying additional hydroxo groups. The use of bi- and tridentate ligands of this type allows the synthesis of mixed-chelate complexes with a number of O N, N N or N S bidentate ligands. The products are of considerable interest for nuclear medical applications as well as for homo-... 

In recent years, it has been shown that co-ordinated phosphines may also undergo reactions with carbonyl compounds. This is well exemplified in the reactions of [(MeHPCH2CH2PHMe)2Pd]2+ (Fig. 5-51). The reaction with formaldehyde yields a complex of an open-chain hydroxymethyl substituted ligand, the same species that is obtained from reaction of the free ligand. This is the phosphorus analogue of the aminol intermediate in imine formation. It is extremely unusual to obtain RP=CR2 systems in the absence of sterically demanding substituents. 

This is also the case for 2-substituted furans, however, mixtures of acetal- and ketal-type oxetanes (e.g., for 87b) were obtained [82]. The use of furans with steric demanding substituents (e.g., 87c) [66a,83], or a acetyl substituent (e.g., 87d) [66b] at the 2-position largely improves the regio-selectivity. A huge number of carbonyl compounds have been investigated in the last 10 years by Zamojski [84] and especially by Schreiber [85] who used furan-carbonyl adducts as intermediates in total synthesis of natural... 

Several papers are concerned with the threo-erythro stereoselectivity of the reaction of allylic organozinc reagents with carbonyl compounds. The addition (involving allylic rearrangement) of crotylzinc derivatives to various aldehydes occurs stereoselectively, and the relative amount of tAreo-alcohol increases with increasing steric demand of the group R tert-Bu, S4% f-Pr, 707o n-Bt, 46%) and in the sequence of metals Mg < Zn < Cd 3, 7). The temperature or the polarity of the solvent... 

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