Substrate-Based Strategies

The enedione intermediate was generated under mild oxidative conditions using A-bromosuccinimide (NBS) and pyridinium para-toluenesulfonic acid (PPTS) and, once formed, the intramolecular reactions occurred spontaneously. The diol substrates underwent the expected NBS-mediated ring expansion followed by bicycloketalization to give [3.2.1]bicycle 13, the single hydroxyl substrates underwent the same ring expansion 

TABLE 4.1. Gemmacin and the Connparable effects of the Enantionners of Gennnnacin, Erythronnycin, and Oxacillin on Three Strains of S. aureus 

In their work, the bmld phase involved the synthesis of a solid-supported methoxy oxazole (20) and various azide-decorated aromatic aldehydes and benzyl bromides. The methoxy oxazole was then able to take part in an enantioselective Suga—Ibata reaction with 

the nitro and alkyne groups could be paired by cycloaddition to give isoxazole-containing bicycles such as 30, and the nitro and ester groups could be paired to give lactams such as 31. 

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In Chapter 27 (Substrate Based Strategy) we shall meet the use of chiral auxiliaries. If you ask someone what properties a good chiral auxiliary should have you will get all the usual suspects - cheap, both enantiomers available, easy to put on, easy to take off, effective at induction etc. However, there is one property that gets very little attention. After the reaction the diastereomers should be separable. Suppose we have a chiral auxiliary 70 with an enantiomeric excess of 96% which reacts... 

Introduction to Substrate-Based Strategy Chiral Carbonyl Groups... 

An advantage of the substrate-based strategy is that the chiral auxiliary is still attached to the molecule after the induction reaction and so the product, 9 in this instance, can be purified as one diastereoisomer before the chiral auxiliary is removed. An example of the asymmetric Strecker reaction in practice is the synthesis of the fat amino acid 16 having an adamantyl group to increase solubility in fats and hence permeability to cell membranes.2 After purification of the amino nitrile 13 hydrolysis gives the amide 14, hydrogenation removes (and sadly destroys) the chiral auxiliary, and a final hydrolysis gives the fat amino acid 16. 

The starting materials in this chapter will already be single enantiomers and will have been made so by one of the methods we have discussed at length over the last eight chapters Resolution (chapter 22), Chiral Pool (23), Asymmetric Reagents (24) Asymmetric Catalysis (25 and 26), Substrate-Based Strategy (27), Kinetic Resolution (28) or Enzymes (29). These strategies will be identified by chapter titles and you are invited to check back if such descriptions are obscure or to check the references for more detail. 

A similar oxazolidine-based strategy was employed in the syntheses of R-(+)-anatabine (84) and (+)-benzomorphan (85), utilizing Zincke-derived salts 80 and 81, respectively (Scheme 8.4.26). In these cases, borohydride reduction, followed by cyclization, led to oxazolidines 82 and 83 as substrates for organometallic addition and subsequent elaboration to the natural products... 

This classical C-P bond-forming reaction (51) has seen limited application in the glyphosate arena, presumably for lack of suitable substrates that can tolerate the vigorous reaction conditions. Typically, C-P bond formation occurs when an alkyl halide reacts with excess neat trialkyl phosphite at temperatures exceeding 100 °C, near the boiling point of the phosphite. An Arbuzov-based strategy for glyphosate requires the synthesis of the... 

Activity-based strategies employ tests that are often applied directly to colonies to identify the desired activity. Nontoxic chemical dyes and insoluble or chromo-phore-bearing derivatives of enzyme substrates, for example, can be incorporated... 

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