Regiochemical and Stereochemical Considerations

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. 

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. 

Proton donors are known to exert considerable influence on the regiochemical and stereochemical outcome of several Sml2-mediated reactions. Yoshida and Mikami (1997) have reported the effect of proton source in the reduction of propargylic phosphates by Palladium(0)/Sml2/proton source system (eq. (42), table 1). The use of 2-methyl-2-propanol as the proton source results in the exclusive formation of allenes, while the diol, dimethyl tartarate ((+)-DMT) gave the alkyne as the major product. 

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. 

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. 

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