by the chirality of the α-carbon on the aldehyde substrate (Figure "Substrate control: addition of achiral allylmetals to α-chiral aldehydes"). The allylmetal reagents used include boron, tin and titanium. Cram’s rule explains the stereoselectivity by considering the transition state depicted in figure 3. In the transition state the oxygen lone pair is able to interact with the boron centre whilst the allyl group is able to add to the carbon end of the carbonyl group. The steric demand of this transition state is minimized by the α-carbon configuration holding the largest group away from (trans to) the congested carbonyl group and the allylmetal group approaching past the smallest group on the α-carbon centre. In the example below (Figure "An example of substrate controlled addition of achiral allyl-boron to α-chiral aldehyde"), (R)-2-methylbutanal (1) reacts with the allylboron reagent (2) with two possible diastereomers of which the (R, R)-isomer is the major product. The Cram model of this reaction is shown with the carbonyl group placed trans to the ethyl group (the large group) and the allyl boron approaching past the hydrogen (the small group). The structure is shown in Newman projection. In this case the nucleophilic addition reaction happens at the face where the hydrogen (the small group) is, producing the (R, R)-isomer as the major product. Chiral auxiliaries Asymmetric stereoinduction can be achieved with the use of chiral auxiliaries. Chiral auxiliaries may be reversibly attached to the substrate, inducing a diastereoselective reaction prior to cleavage, overall producing an enantioselective process. Examples of chiral auxiliaries include, Evans’ chiral oxazolidinone auxiliaries (for asymmetric aldol reactions) pseudoephedrine amides and tert-butanesulfinamide imines. Substrate control: asymmetric induction by molecular framework in cyclic systems Cyclic molecules often exist in much more rigid conformations than their linear counterparts. Even very large macrocycles like erythromycin exist in defined geometries despite having many degrees of freedom. Because of these properties, it is often easier to achieve asymmetric induction with macrocyclic substrates rather than linear ones. Early experiments performed by W. Clark Still and colleagues showed that medium- and large-ring organic molecules can provide striking levels of stereo induction as substrates in reactions such as kinetic enolate alkylation, dimethylcuprate addition, and catalytic hydrogenation. Even a single methyl group is often sufficient to bias the diastereomeric outcome of the reaction. These studies, among others, helped challenge the widely-held scientific belief that large rings are too floppy to provide any kind of