Improving Reaction Yield

To improve reaction yields, there are two possible pathways to add excess substrate (typically the amine donor) or to remove product(s). Addition of excess substrate imphes that the enzyme would have to remain stable and function at high concentration of substrate amine. Typically, isopropylamine is used as the amine donor as it is a relatively inexpensive raw material that allows its use in high 

1) Remove product ketone from reaction mixture by 

2) Remove product amine from the reaction mixture by 

Similarly, enzyme modification is required to increase throughput and to reduce enzyme usage in the reaction. High temperature was used successfully to increase the rate of reaction and simultaneously allow removal of acetone from the reaction to shift equilibrium by the development of a thermostable enzyme capable of activity at 55 °C. Another major problem could be poor selectivity of the enzyme resulting in low chiral purity of the product amine. This requires modification of the enzyme and 

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Microwave irradiation has recently become a possible method to improve reaction yields and dramatically shorten reaction times. Numerous types of reaction with highly enhanced rates have been found, and very high yields and clean reactions have been obtained by applying only small amounts of energy. ... 

Various laboratories, in an effort to improve reaction yield and stereoselectivity, have made targeted modifications on the core structure of the oxazaborolidine catalyst."1 Figure 2 illustrates the level of stereocontrol in the CBS reduction of acetophenone as the R-group was systematically investigated to assess the varying degrees of enantiocontrol. The best... 

A significant niunber of variations on the Niementowski reaction have been developed over the years in an effort to improve reaction yields and product purity. The most common modifications involve the use of imidates, imidoylchlorides, dithiazoles, benzonitriles, or amidines. Select examples of these modifications are highlighted below. 

Additional modifications to the Hantzsch 1,4-dihydropyridine synthesis generally involve the use of activated methylene compounds such as 1,3-diketones, co-cyanoacetophenone, co-phenylacetophenone, a, P-unsaturated ketones, and indane-l,3-diones. A number of efforts to improve reaction yields using eatalysts have also been reported, including the use of hydrotalcite materials, triphenylphosphine copper II triflate, and covalently anchored sulfonic acid on silica gel. Dihydropyridine synthesis has also recently been studied with high success using microwave and solvent-free" reaction conditions. 

The Goldberg catalysed Y-arylation of amides gives low yields and requires drastic reaction conditions, but the use of silica-supported copper improves reaction yields. The pyrazolodiazepin system has been A -hetero-arylated in this way using potassium acetate as a base (e.g. equation 4.8) [52]. 

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