Catalytic asymmetric synthesis evolution

Since the first edition of Catalytic Asymmetric Synthesis in 1993 the pace of innovative discoveries in the area of asymmetric catalysis of the aldol reaction has been breathtaking [3,4]. The fast-paced evolution is evident in the significant improvements in substrate generality, experimental simplicity, catalytic loading, and the enantiopurity of the adducts isolated. In parallel with these advances in preparative chemistry of catalytic aldol addition processes, there has been increased sophistication in our understanding of the mechanistic aspects of the wide-ranging transforms included in the aldol rubric. 

FROM CATALYTIC ASYMMETRIC SYNTHESIS TO THE TRANSCRIPTIONAL REGULATION OF GENES IN VIVO AND IN VITRO EVOLUTION OF PROTEINS... 

An intramolecular diastereoselective Refor-matsky-type aldol approach was demonstrated by Taylor et al. [47] with an Sm(II)-mediated cy-clization of the chiral bromoacetate 60, resulting in lactone 61, also an intermediate in the synthesis of Schinzer s building block 7. The alcohol oxidation state at C5 in 61 avoided retro-reaction and at the same time was used for induction, with the absolute stereochemistry originating from enzymatic resolution (Scheme II). Direct re.solution of racemic C3 alcohol was also tried with an esterase adapted by directed evolution [48]. In other, somewhat more lengthy routes to CI-C6 building blocks, Shibasaki et al. used a catalytic asymmetric aldol reaction with heterobimetallic asymmetric catalysts [49], and Kalesse et al. used a Sharpless asymmetric epoxidation [50]. 

The rapid evolution of catalytic reaction methods for enantioselective aldol additions affords newer processes that are increasingly practical in their execution for a broad range of substrates prescribing minuscule amounts of catalyst. However, when compared to other catalytic asymmetric processes such as hydrogenation, dihydroxylation, and epoxidation it is evident that there is much room for further optimization. Without doubt, discovery and innovation in this area of C-C bond-forming reactions will lead to the development of catalysts and processes indispensable to the synthesis of optically active, stereochemically complex structures with applications in materials science and medicine. 

Both enantiomers of BINAP are very useful ligands for various catalytic asymmetric reactions.5 However, the scarce supply and high cost of BINAP somewhat limit their wide application. A previously reported synthesis of BINAP was not easy to scale up because of potentially hazardous conditions (320°C with HBr evolution), and low overall yield.6 This procedure presents a short and efficient process to chiral BINAP from readily available chiral 1,1 -bi-2-naphthol. 

In the realm of olefin hydrometalation, the hydroboration reaction has largely dominated the scene. This is in no small part due to the early work by Brown in the development of this reaction class to a level of sophistication that permitted its evolution as a reliable and common tool in the service of complex molecule synthesis. There are, however, closely related catalytic asymmetric hydrometalation reactions of olefins that provide alternatives to enantioselective hydroboration namely, the hydroalumination [14] and hydrosilylation reactions [16]. 

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