- Efficient Biocatalytic Reductive Aminations by Extending the Imine Reductase Toolbox
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Chiral secondary and tertiary amines are ubiquitous in pharmaceutical, fine, and specialty chemicals, but their synthesis typically suffers from significant sustainability and selectivity challenges. Biocatalytic alternatives, such as enzyme-catalyzed reductive amination, offer several advantages over traditional chemistry, but industrial applicability has not yet been demonstrated. Herein, we report the use of cell lysates expressing imine reductases operating at 1:1 stoichiometry for a variety of amines and carbonyls. A collection of biocatalysts with diversity in coverage of small molecules and direct industrial applicability is presented.
- Roiban, Gheorghe-Doru,Kern, Marcelo,Liu, Zhi,Hyslop, Julia,Tey, Pei Lyn,Levine, Matthew S.,Jordan, Lydia S.,Brown, Kristin K.,Hadi, Timin,Ihnken, Leigh Anne F.,Brown, Murray J. B.
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p. 4475 - 4479
(2017/12/07)
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- Rapid and efficient access to secondary arylmethylamines
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Ammoniomethyl trifluoroborates are very powerful reagents that can be used to access biologically relevant aryl- and heteroaryl-methylamine motifs via Suzuki-Miyaura cross-couplings. Until now, this method was limited to the production of tertiary and primary amines. The synthesis of a large array of secondary ammoniomethyltrifluoroborates has been achieved through a one step nucleophilic substitution reaction on the potassium bromomethyltrifluoroborate. Smooth cross-coupling conditions have been designed, based on the use of an aminobiphenyl palladium precatalyst, to couple these trifluoroborates efficiently with aryl bromides. This strategy offers a new way to access biologically relevant motifs and allows, with the previously developed methods, access to all three classes of aminomethylarenes. Secondary ammoniomethyltrifluoroborates can be easily synthesized by nucleophilic substitution on potassium bromomethyltrifluoroborate. These reagents have then been used in Suzuki-Miyaura cross-couplings with aryl bromides, offering an effective access to the aminomethylarene structural motif. This new method provides an interesting alternative to the reductive amination procedure (see scheme). Copyright
- Fleury-Brégeot, Nicolas,Raushel, Jessica,Sandrock, Deidre L.,Dreher, Spencer D.,Molander, Gary A.
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supporting information; experimental part
p. 9564 - 9570
(2012/08/28)
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