Recent advances in acyclic stereocontrol

Recent developments in models for acyclic stereocontrol have been discussed in the context of three important classes of organic reaction and some recent organometallic reactions. For additions of nucleophiles to carbonyls with an adjacent stereocentre, both computational and experimental evidence have challenged the predominance of the FelkineAnh and Cram models for predicting stereoselectivity. Various models for describing electrophilic and nucleophilic addition to double bonds have been proposed that account for variations in selectivity. However, these are often very specific to each particular reaction. In some cases, the major product arises from a seemingly highenergy transition state, e.g., in examples of the inside-methyl effect. Above all, 1,3-allylic strain appears to be the most important control element in reactions of C]C double bonds adjacent to a stereocentre. Many of the same models have been extended to explain acyclic stereocontrol in pericyclic reactions. In these cases, both stereoelectronic effects, again 1,3-allylic strain in particular, and electrostatic effects must be taken into account. Stereoselective reactions of unsaturated functional groups adjacent to organometallic complexes are also emerging as useful tools for establishing acyclic stereocontrol. Taking into account the above examples, some general conclusions can be drawn. There is no unified theory that explains all modes of acyclic stereocontrol. Rather, it appears that models are very specific to the individual reaction mechanism, and the nature of the incoming electrophile or nucleophile must be considered. Additional complexity is encountered when stereoselectivity is a function of both acyclic and cyclic stereocontrol (double diastereoselection). These cannot be considered in isolation and models must take into account interactions between cyclic and acyclic transition states. Developments in computational methods have contributed to our ability to predict the sense of acyclic stereocontrol,although exceptions to these predictions are often encountered in experiments. Development of models and methods for establishing acyclic stereocontrol remains a highly active area of interest in synthetic chemistry. © 2011 Elsevier Ltd. All rights reserved.