Heteroatom-directed carbon-hydrogen

With more than 100 elements besides carbon in the periodic table (Appendix 2), you might fear that the number of H chemical shift correlations is endless. However, except for a few specialized applications, the most important heteroatoms to which hydrogen finds itself bonded are oxygen and nitrogen. But before we discuss these two specific cases, here is a useful generalization As the electronegativity (Table 6.1) of X increases, both the acidity and chemical shift of a hydrogen bonded directly to X increase. 

Carbon-Hydrogen Bond Insertion In the early 1960s the activation of alkanes by metal systems was realized from the related development of oxidative addition reactions " " in which low-valent metal complexes inserted into carbon-heteroatom, silicon-hydrogen, and hydrogen-hydrogen bonds. The direct oxidative addition of metals into C-H bonds was found in the cyclometallation reaction [Eq. (6.61)].The reverse process of oxidative addition is called reductive elimination, which involves the same hypercoordinate carbon species. 

Direct arylation [9, 10], is a reaction formally similar to cross-coupling, with the key difference that one of the carbons involved in the process is not bound to a heteroatom, but to hydrogen (Eq. 11.6). 

The direct conversion deals with the straight hydrogenation of carbon monoxide to paraffins, olefins and heteroatom (oxygen, nitrogen) containing products. The indirect conversion invokes intermediates such as methanol, methyl formate and formaldehyde. The latter ones in a consecutive reaction can yield a variety of desired chemicals. For instance, acetic acid can be synthesized directly from CO/H2, but for reasons of selectivity the carbonylation of methanol is by far the best commercial process. 

The major focus in this chapter will be on synthesis, with emphasis placed on more recent applications, particularly those where regiochemistry and stereochemistry are precisely controlled. The reader is referred to the earlier reviews for full mechanistic information and details of historic interest. Electrophilic addition of X—Y to an alkene, where X is the electrophile, gives products with functionality Y (3 to the heteroatom X. Further transformations of X and/or Y provide the basis for diverse synthetic applications. These transformations include replacement of Y by hydrogen, elimination to form a ir-bond (either including the carbon bonded to X or (3 to that carbon so that X is now in an allylic position), and nucleophilic or radical substitution. Representative examples of these synthetic methods will be given below. This chapter will include examples of heterocycles formed in one-pot reactions where the the initial alkene-electrophile adduct contains an electrophilic group that can react further. Examples of heterocycles formed in several steps from alkene-electrophile adducts will also be considered. Cases in which activation by an external electrophile directly results in addition of an internal heteroatom nucleophile are treated in Chapter 1.9 of this volume. 

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