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Catalysis Science & Technology
DOI: 10.1039/C6CY00855K
COMMUNICATION
Journal Name
Scheme 2. Chemo-enzymatic strategy for the synthesis of biarylalanine 4 from 1j, consisting of PAL amination, N-protection and Suzuki-
Miyaura coupling. Examples of pharmaceutical ingredients or candidates containing the substructure of 4 are shown in blue.
The 100% atom efficient synthesis has been achieved on a
commercially-relevant scale - a considerable improvement on
current industrial methods. The use of cheap, raw ammonium
carbamate as a high-concentration ammonia donor salt lessens the
work associated with producing high molarity, pH adjusted buffers
and allows the equilibrium of the reaction to be driven towards
product formation, due to its high solubility and ammonia content.
The nature of the reaction mixture, combined with the optimised
conversions (>95%) allow easy crude isolation of the amino acid
products to a good level of purity - sufficient to enable easy
modular integration with further chemical steps.
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Acknowledgements
th
This work was funded by the European Union’s 7 Framework
program FP7/2007-2013 under grant agreement no. 289646
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grant initiative ref. BB/K00199X/1. We thank the Royal Society for a 15
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