In line with the principles of “green” chemistry, organocatalysis seeks to reduce energy consumption and to optimize the use of the available resources, aiming to become a sustainable strategy in chemical transformations. Nevertheless, during the last decade diverse experimental protocols have made organocatalysis an even “greener” alternative by the use of friendlier reaction conditions, or via the application of solvent-free methodologies, or through the design and synthesis of more selective catalysts, or via the development of multicomponent one-pot organocatalytic reactions, or by the recycling and reuse of organocatalysts, or by means of the application of more energy-efficient activation techniques, among other approaches. In this feature article we review some of the remarkable advancements that have made it possible to develop even more sustainable asymmetric organocatalyzed methodologies.

The introductory section of this review presents some of the currently most compelling β-amino acid targets, according to their structural types: (α and β-aryl substituted, olefinic and alkynyl, α,α- and α,β-disubstituted, 'cyclic and conformationally restricted, fluorine­ containing, and phosphonic analogous β-amino acids. The main section highlights some of the very new (1996-1998), promising methodology for the enantioselective synthesis of β-amino acids, with especial emphasis on catalytic and enzymatic processes, as well as methods based on "chiral pool", "self-regeneration of stereogenic centers", diastereoselective nucleophilic additions to prochiral double bonds, and enantioselective reactions in the presence of chiral additives.

Although known for millennia, it is only recently that mechanochemistry has received serious attention by chemists. Indeed, during the past 15 years an extraordinary number of reports concerning solid-state chemical transformations through grinding and milling techniques have been recorded. This short review discusses the circumstances that led this renaissance, highlighting the present intense interest in so-called green chemistry, the enabling capacity of mechanochemistry to handle insoluble substrates, and the identification of the profound influence that additives can have on mechanochemically activated reactions. The core of this account focuses on salient developments in synthetic organic chemistry, especially in amino acid and peptide­ mechanosynthesis, the successful employment of mechanochemical activation in combination with asymmetric organocatalysis, the promising combination of mechanochemical activation with enzymatic and whole cell biocatalysis, the remarkable achievement of multicomponent selective reactions via complex, multistep reaction pathways, and the mechanosynthesis of representative heterocycles. The final section comments on some pending tasks in the area, such as scaling-up of milling processes to be of practical use in the chemical industry, the requirement of easier and more efficient control of reaction parameters and monitoring devices, and consequently the careful analysis of additional procedures for a proper understanding of mechanochemical phenomena.1 Introduction2 Brief History of Mechanochemistry3 Milling Equipment and Reaction Parameters4 Attributes of Mechanochemistry That Propelled Its Present Renaissance4.1 Enormous Attention Being Presently Paid to Sustainable Chemistry4.2 Reduced Energy Consumption4.3 Additive-Based Mechanochemistry4.4 Handling of Insoluble Reactants4.5 ‘Impossible’ Reactions That Are Successful by Milling4.6 Successful Handling of Air- and Water-Sensitive Reagents by Ball Milling5 Salient Developments in the Mechanochemical Activation of Synthetic Organic Chemistry5.1 Amino Acid and Peptide Mechanosynthesis5.2 Asymmetric Organic Synthesis and Asymmetric Organocatalysis under Ball-Milling Conditions5.3 Mechanoenzymology5.4 Multicomponent Reactions Activated by Mechanochemistry5.5 Mechanosynthesis of Heterocycles and Modification of Heterocycles6 Future Directions6.1 Scaling-Up Mechanochemical Protocols6.2 Temperature-Controlled Mechanochemistry6.3 Understanding Mechanochemical Transformations6.4 Emerging Mechanochemical Techniques7 Conclusions

This Account describes convenient procedures for the preparation of several enantiopure β-amino alcohols and β-diamines, which have proved to be efficient ligands in relevant ste­reoselective reactions such as alkylation of enolates and hydrogenation of carbonyl compounds. Furthermore, the title compounds are useful precursors of various chiral oxazolidinones, oxazinones, phosphonamides, etc., which allow the enantioselective formation of a wide variety of chiral derivatives, including alcohols, aldol condensation products, aminophosphonic acids, sulfoxides, and others, as well as the development of derivatizing reagents for the determination of enantiomeric purity in chiral alcohols and chiral amines.