Elimination/addition reactions synthetic strategies

Chiral cyclohexanones obtained by the Ferrier carbocyclization reaction are useful precursors for the synthesis of cyclitols and aminocyclitols, some of which are found in clinically important aminoglycoside antibiotics. Additionally, highly substituted cyclohexenones, prepared by the Ferrier carbocyclization followed by (3-elimination, can undergo various further transformations, also making these compounds potential chiral building blocks for the preparation of structurally complex compounds having cyclohexane unit(s). This section provides an overview of the reported synthetic strategies toward various types of natural products based on utilization of the Ferrier carbocyclization reaction. 

Among the successful synthetic strategies for carbocyclic compounds that have been introduced can be found the phenylthio radical-catalyzed multiple radical reactions (see Scheme 6). This sequential transformation has also been termed, in a more general context, as addition-elimination methodology [9]. 

Although a great variety of synthetic strategies is known to afford hypercoordinated silicon compounds, they can be classified as addition (and sometimes elimination), substitution, and rearrangement reactions or combinations thereof. 

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

The fragmentation strategy is based on a similar concept to traceless solid-phase chemistry, like retrocycloaddition cleavage, cycloelimination or cyclofragmentation. These are synthetically useful reactions with wide scope for the construction of rigid templates of different ring sizes. Up to now only one example for the attachment of heteroatoms via addition/elimination strategy has been developed, by Kurth et al. (Scheme 3.7) [188, 189]. 

Abstract With the advent of new synthetic methodologies, carbon-carbon bond (C-C) activation strategies have uncovered not only new fundamental reactivity but also the potential for use as a highly efficient synthetic protocol. This chapter specifically discusses the use of four-membered ketone-based starting materials for C-C activation initiated transformations using a variety of transition metals. The two major modes of activation, oxidative addition and p-C elimination, are presented as each pathway shows different mechanistic details and the ability to effect several types of reactions. Applications to the synthesis of complex molecules are presented and perspectives on future applications are considered. 

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