Enantiotopic discrimination asymmetric synthesis

Hydrolytic enzymes such as esterases and Upases have proven particularly useful for asymmetric synthesis because of their abiUties to discriminate between enantiotopic ester and hydroxyl groups. A large number of esterases and Upases are commercially available in large quantities many are inexpensive and accept a broad range of substrates. 

Asymmetric synthesis (1) Use a chiral auxiliary (chiral acetal—the synthetic equivalent of an aldehyde chiral hydrazone—the synthetic equivalent of a ketone) covalently attached to an achiral substrate to control subsequent bond formations. The auxiliary is later disconnected and recovered, if possible. (2) Use a chiral reagent to distinguish between enantiotopic faces or groups (asymmetric induction) to mediate formation of a chiral product. The substrate and reagent combine to form diastereomeric transition states. (3) Use a chiral catalyst to discriminate enantiotopic groups or faces in diastereomeric transition states but only using catalytic amounts of a chiral species. 

The potential utility of an asymmetric addition to a prochiral carbonyl can be seen by considering how one might prepare 4-octanol (to take a structurally simple example) by asymmetric synthesis. Figure 4.16 illustrates four possible retro-synthetic disconnections. Note that of these four, two present significant challenges asymmetric hydride reduction requires discrimination between the enantiotopic faces of a nearly symmetrical ketone a), and asymmetric hydroboration-oxidation requires a perplexing array of olefin stereochemistry and regiochemical issues h). In contrast, the addition of a metal alkyl to an aldehyde offers a much more realistic prospect (c) or (d). 

Stereoisomerism and Connectivity 300 Total Synthesis of an Antibiotic with a Staggering Number of Stereocenters 303 The Descriptors for the Amino Acids Can Lead to Confusion 307 Chiral Shift Reagents 308 C2 Ligands in Asymmetric Synthesis 313 Enzymatic Reactions, Molecular Imprints, and Enantiotopic Discrimination 320 Biological Knots—DNA and Proteins 325 Polypropylene Structure and the Mass of the Universe 331 Controlling Polymer Tacticity—The Metallocenes 332 CD Used to Distinguish a-Helices from [3-Sheets 335 Creating Chiral Phosphates for Use as Mechanistic Probes 335... 

The asymmetric cyclisation of achiral olefinic organohthium reagents by a stereogenic alkah metal centre can be modulated by ( )-sparteine, which confers enantiofacial selectivity on the reaction such that the anionic cyclisation process discriminates between the enantiotopic faces of an unactivated C=C bond. Recently, modifications have been made to the well known hthium-ene cyclisation reaction whereby the subsequent expulsion of a thiophenoxide group yields a fused vinylcyclopropane. Moreover, allylic lithium oxyanion-induced reactivity and stereoselectivity in this intramolecular carbometallation has been demonstrated in the highly stereoselective synthesis of a natural bicyclo[3.1.0] hexane. ... 

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