Control of stereochemistry during aldol addition reactions has attracted considerable interest over the years as the aldol reaction is one of the most fundamental tools for the construction of new carbon-carbon bonds. Several strategies have been implemented whereby eventually any single possible stereoisomeric aldol product can be accessed by choosing the appropriate procedure. With earlier methods, stoichiometric quantities of chiral reagents were required for efficient asymmetric induction, with the auxiliary most often attached covalently to the substrate carbonyl. Lewis acid catalyzed addition reactions of silyl enolates to aldehydes (Mukaiyama reaction) later opened the way for catalytic asymmetric induction. In the last few years, both chiral metal complexes and small chiral organic molecules have been found to catalyse the direct aldol addition of unmodified ketones to aldehydes with relatively high chemical and stereochemical efficiency. These techniques along with the more recent developments in the area are discussed in this tutorial review.

Remarkably high and regular enantioselectivities are obtained in Friedel-Crafts alkylation reactions involving alpha'-hydroxy enone templates and Cu(II)-bis(oxazoline) complexes as catalysts. The simple elaboration of adducts provides a route to enantioenriched aldehydes, carboxylic acids, and ketones containing the pyrrole and indole frameworks.

The main recent conceptual advances in asymmetric aldol reactions are presented. Methods ranging from stoichiometric chiral auxiliary-mediated to direct, catalytic reactions are covered, including the Mukaiyama aldol reactions which use stoichiometric base and silylating reagents, but catalytic (substoichiometric) amounts of the chiral inductor. The salient features of each new development are noted, paying special attention to practical concerns and to the potential implementation for large scale production. After examination of pros and cons of each strategy, gaps and limitations that deserve further investigation are highlighted.

Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Brønsted base (BB) catalysis and the use of α'-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α'-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α'-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.

Approaching the Nature's efficiency in controlling both reactivity and stereoselectivity of organic reactions by means of a catalyst species remains a formidable challenge for chemists to face. Despite impressive advances in the design of novel catalysts and activation modes, current catalytic and asymmetric methodologies rarely meet desirable standards of robustness, substrate scope, and selectivity altogether. One trick to improve catalyst behaviour is to identify adequate substrate template-catalyst combinations so that optimum performance of the reaction system could be achieved. During the last couple of years α-hydroxy ketones, and most particularly α'-hydroxy enones, have emerged as useful templates with applications in a number of metal-catalyzed as well as organocatalyzed C-C and C-X bond-forming stereoselective reactions. The first review of these accomplishments is presented here along with a brief historical introduction.

Catalytic, asymmetric conjugate addition of carbamates to enoyl systems has been realized for the first time, providing a two-step access to virtually enantiopure N-protected beta-amino acids.

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