Non-racemic chiral boronic esters are recognised as immensely valuable building blocks in modern organic synthesis. Their stereospecific transformation into a variety of functional groups-from amines and halides to arenes and alkynes-along with their air and moisture stability, has established them as an important target for asymmetric synthesis. Efforts towards the stereoselective synthesis of secondary and tertiary alkyl boronic esters have spanned over five decades and are underpinned by a wealth of reactivity platforms, drawing on the unique and varied reactivity of boron. This Review summarizes strategies for the asymmetric synthesis of alkyl boronic esters, from the seminal hydroboration methods of H. C. Brown to the current state of the art.

In recent years there has been an accelerated rate of development in the field of organocatalysis, with asymmetric organocatalysis now reaching full maturity. The invention of new organocatalytic reactions and the exploration of new concepts now appear in tandem with the application of organocatalytic techniques in the synthesis of natural products and active pharmaceutical ingredients (APIs). After a "golden rush" in organocatalysis, researchers are now starting to combine different methods, thereby taking advantage of the significant benefits of synergy. Metals are used in combination with organocatalytic processes, thus reaching complexity that is found in nature, where enzymes take advantage of the presence of certain metals to increase the arsenal of organic transformations available. In this Focus review, we illustrate the possibility of a "happy marriage" between Lewis acids and organocatalytic stereoselective processes. Questions have been raised about the combination of Lewis acids and organocatalysis owing to the presence of water and/or strong bases in these processes. Some Lewis acids have been shown to be compatible with organocatalysis and concepts relating to their use will be illustrated herein. To summarize the fruitful use of Lewis acids in stereoselective organocatalytic processes, we will draw attention to the advantages and selectivity achieved using this method.

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The coupling of ortho‐ and para‐phenols with secondary and tertiary boronic esters has been explored. In the case of para‐substituted phenols, after reaction of a dilithio phenolate species with a boronic ester, treatment with Ph3BiF2 or Martin's sulfurane gave the coupled product with complete enantiospecificity. The methodology was applied to the synthesis of the broad spectrum antibacterial natural product (−)‐4‐(1,5‐dimethylhex‐4‐enyl)‐2‐methyl phenol. For ortho‐substituted phenols, initial incorporation of a benzotriazole on the phenol oxygen atom was required. Subsequent ortho‐lithiation and borylation gave the coupled product, again with complete stereospecificity.

Best of both worlds: Organocatalytic SN1‐type reactions promoted by indium(III) salts were performed with activated benzylic and benzhydrylic substrates. High ee values and moderate diastereomeric ratios were obtained. The presence of a 4‐NMe2Ph group, which is useful for further transformations, is essential for obtaining high yields. The synergy of indium(III) salts with organocatalysis is a useful strategy for stereoselective transformations.