Factors That Influence Reaction Regioselectivity

Factors That Influence Reaction Regioselectivity 1. Tributylstannyl Ethers 

When a polyol is reacted with bis(tributyltin) oxide, all tributylstannyl ethers are formed and these interconvert readily at the reaction temperatures.35-36 Ogawa and Matsui suggested that oxygen atoms of tributyltin ethers that have adjacent oxygen atoms in appropriate orientations to coordinate with the tin atom are activated toward electrophiles74,75 specifically, equatorial oxygen atoms that have an adjacent axial oxygen atom, 

Although the factors that influence the regioselectivities obtained from dialkylstannylene acetals are considerably more complicated than with tributylstannyl ethers, the outcome in most cases is surprisingly similar. The factor influencing regioselectivity in the absence of added nucleophiles will be discussed first. 

The causes of the regioselectivity of these reactions are complicated, because acyl and silyl groups can rearrange under these conditions (see later discussion) and because added nucleophiles are also used. To simplify the discussion, p-toluenesulfonylation reactions, performed without added nucleophiles, are discussed first. It has been established that the products of these reactions do not rearrange.20 

Monomers are unlikely to be intermediates in these reactions, because they are much less populated than dimers and because their oxygen atoms would not be expected to be more reactive than those of the dimers. Any gain in reactivity conveyed by decreased steric hindrance to electrophile approach would be offset by the increased electron density on tin that presumably accompanies dimer formation. Since the same considerations apply to oligomer reactions as apply to dimer reactions, and since oligomers are usually much less populated, reactions conducted in the absence of added nucleophiles are discussed only in terms of dimers. 

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In addition to enantiocontrol, the problem of regiocontrol arises in these reactions. There are various factors that influence the regioselectivity of allylic substitutions [3,4,13, 36, 37, 38, 39]. Electronic effects exerted by the catalyst and the allylic substituents, steric interactions between the nucleophile, the allyl system and the catalyst, and the relative stabilities of the Ti-olefin complexes formed after nucleophilic addition, can all play a role. The relative importance of these factors varies with the catalyst, the substrate, the nucleophile, the solvent and other reaction parameters and is difficult to predict. 

Recent advances in the rhodium-catalyzed [4-1-2] reactions have led to the development of the first highly regioselective intermolecular cyclization, providing access to new classes of carbocycles with both activated and unactivated substrates. The chemo- and stereoselective carbocyclizations of tethered diene-allene derivatives afford new classes of 5,6- and 6,6-bicyclic systems. Additionally, examination of a wide range of factors that influence both diastereo- and enantioselectivity has provided a significant advance in the understanding of catalyst requirements across these systems. 

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