Regiochemical Considerations

An important recent advance in the area is the demonstration that allyl chlorides readily form allylcopper species upon exposure to highly activated copper ( Rieke copper ). The resultant allylcoppers have been shown to react with a fairly wide range of nucleophiles (ketones, aldehydes, acid chlorides, enones, epoxides [after conversion to the cuprate], imines, and allyl bromides)56. Regiochemical considerations in such substitutions depend upon the cases studied, and are fairly complex. The allylcoppers formed have, in all cases, the least substituted C—Cu bond allyl transfer from these reagents is selective from the imposition of the allyl (enone electrophiles excepted)(equations 41 and 42). The allyl chloride... 

Whereas Scheme 13.6 focuses on the kinetics of stereochemical changes to R)-3h induced by its photolyses. Scheme 13.7 focuses on regiochemical considerations of product formation. Scheme 13.7 links in-cage formation of 2-BN and 4-BN to specific, regio-isomeric radical pairs, [radical pair]2B and [radical pair]4B, and Equation 13.16 can be derived from it. 

Complementary to catalytic hydrogenations, the use of diborane provides convenient routes towards the elimination of olefins. However, this reaction has the added advantage of introducing new functionality at the site of olefin reduction. Because of regiochemical considerations, this reaction is particularly useful when applied to exocyclic olefins. Scheme 6.76 shows that a sugar derivative was treated with diborane with an oxidative workup to yield the illustrated product bearing a new hydroxyl group exclusively at the primary center [117]. 

The shifting of electrons as shown in the scheme should be taken as a simplified depiction only. A more thorough understanding follows from consideration of the frontier orbitals and their coefficients this may then permit a prediction of the regiochemical course of the cycloaddition. 

Removal of the carbonate ring from 7 (Scheme 1) and further functional group manipulations lead to allylic alcohol 8 which can be dissected, as shown, via a retro-Shapiro reaction to give vinyl-lithium 9 and aldehyde 10 as precursors. Vinyllithium 9 can be derived from sulfonyl hydrazone 11, which in turn can be traced back to unsaturated compounds 13 and 14 via a retro-Diels-Alder reaction. In keeping with the Diels-Alder theme, the cyclohexene aldehyde 10 can be traced to compounds 16 and 17 via sequential retrosynthetic manipulations which defined compounds 12 and 15 as possible key intermediates. In both Diels-Alder reactions, the regiochemical outcome is important, and special considerations had to be taken into account for the desired outcome to. prevail. These and other regio- and stereochemical issues will be discussed in more detail in the following section. 

Many reactions mediated by Sml2 require the presence of a proton donor. The primary role of the proton donor is to quench alkoxides and carbanions produced as intermediates upon reduction or reductive coupling. The most commonly utilised proton donors are alcohols, glycols and water. It is now very clear, however, that proton donors can have a considerable impact on the efficiency of Sml2-mediated reactions and their regiochemical and stereochemical outcome. Often, even a modest change in the proton donor or its concentration can have a profound impact on product distributions. Two important examples of this phenomenon are discussed below. 

Vinyloxiranes react with nucleojAiles in three regiochemically distinct ways with a, 3 and vinyl-ogous modes of opening. The subject has been of considerable interest in the context of acyclic stereoselection and generation of allylic alcohols in an iterative fashion. 

The unusual regiochemical and stereochemical features that are part of both the formation of imine anions and their subsequent reaction as nucleophiles have spawned considerable interest in deriving details of the bonding, especially of the metal, in these species. 

Consideration of the generalized aflatoxin structure represented in (I) leads one to the inescapable conclusion that at the core of the system is the A-ring in the form of a phloroglucinol nucleus, in which each of the pendant phenolic oxygen atoms is uniquely differentiated. Furthermore, two of the three carbon sites on this nucleus are differentially substitued with carbon moieties. This constitutes a potentially difficult synthetic circumstance in that not only must a high degree of substitution be provided for, but also a certain amount of regiochemical control must... 

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