Structure and Reactions of Carbocation Intermediates

Organosilicon compounds are widely used in organic synthesis. The understanding of the structure and properties of the intermediates involved in their reactions is a prerequisite for further development and optimization of useful synthetic transformations involving silicon substituted compounds. Trialky lsilyl-substituted carbocations are particularly... 

The major carbon centered reaction intermediates in multistep reactions are carbocations (carbenium ions), carbanions, free radicals, and carbenes. Formation of most of these from common reactants is an endothermic process and is often rate determining. By the Hammond principle, the transition state for such a process should resemble the reactive intermediate. Thus, although it is usually difficult to assess the bonding in transition states, factors which affect the structure and stability of reactive intermediates will also be operative to a parallel extent in transition states. We examine the effect of substituents of the three kinds discussed above on the four different reactive intermediates, taking as our reference the parent systems [CH3], [CHi]", [CHi] , and [ CH2]. 

Carbocation intermediates are involved and the structure and stereochemistry of the product are determined by the factors that govern substituent migration in the carbocation. Clean, high-yield reactions can be expected only where structural or conformational factors promote a selective rearrangement. Boron trifluoride is frequently used... 

Recentiy published crystal structures of antibody 4C6, an antibody that catalyzes another cationic cyclization reaction (Figure 6), revealed that this antibody has exquisite shape complementarity to its eliciting hapten 5. The active site contains multiple aromatic residues which shield the high-energy intermediate from solvent and stabilize the carbocation intermediates through cation-7r interactions. 

Positively charged amines that are structural analogues and are isosteric with putative carbocation intermediates in enzymic reactions. These compounds have proved their value in efforts to characterize enzyme mechanisms that proceed by the transient formation of carbocation intermediates. 

One of the most direct ways to produce diastereomers is by addition reactions across carbon-carbon double bonds. If the structure of the olefin substrate is such that two new chiral centers are produced by the addition of a particular reagent across the double bond, then diastereomers will result. For example, the addition of HBr to Z-3-chloro-2-phenyl-2-pentene produces 2-bromo-3-chloro-2-phenylpentane as a mixture of four diastereomers. Assuming only Markovnikov addition, the diastereomers are produced by the addition of a proton to C-3 followed by addition of bromide to the carbocation intermediate at C-2. Since the olefin precursor is planar, the proton can add from either face, and since the carbocation intermediate is also planar and freely rotating, the bromide can add to either face to give diastereomeric products. The possibilities are delineated schematically (but not mechanistically) below. 

In many respects the Pummeter reaction can be regarded as the sulfur version of the Polonovski reaction (and vice versa), and by analogy to the Polonovski reaction the central intermediate is a sulfur-stabilized carbocation (thionium ion). Although the existence of this species is only transient, it reacts to give a number of different products, e.g. a-acetoxy sulfides, vinyl sulfides, cationic cyclization products, etc., depending upon the sulfoxide structure and reaction conditions. Other reaction pathways ate specific to the Pummerer reaction as a result of sulfur s ability to expand its valence shell (additive Pum-merer reactions). A moderate degree of asymmetric induction is also observed in certain Pummerer reactions, where optically pure sulfoxides are substrates. 

The mechanism of the substitution reaction depends on the structure of the alcohol. Secondary and tertiary alcohols undergo SnI reactions. The carbocation intermediate formed in the SnI reaction has two possible fates It can combine with a nucleophile and form a substitution product, or it can lose a proton and form an elimination product. However, only the substitution product is actually obtained, because any alkene formed in an elimination reaction will undergo a subsequent addition reaction with HX to form more of the substitution product. 

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