Tandem palladium and isothiourea relay catalysis : enantioselective synthesis of α-amino acid derivatives via allylic amination and [2,3]-sigmatropic rearrangement
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A tandem relay catalytic protocol using both Pd and isothiourea catalysis has been developed for the enantioselective synthesis of α-amino acid derivatives containing two stereogenic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succinimide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by the isothiourea benzotetramisole forms syn-α-amino acid derivatives with high diastereo- and enantioselectivity. This methodology is most effective using 4-nitrophenylglycine esters and tolerates a variety of substituted cinnamic and styrenyl allylic ethyl phosphates. The use of challenging unsymmetrical N-allyl-N-methylglycine esters is also tolerated under the catalytic relay conditions without compromising stereoselectivity.
Spoehrle , S S M , West , T H , Taylor , J E , Slawin , A M Z & Smith , A D 2017 , ' Tandem palladium and isothiourea relay catalysis : enantioselective synthesis of α-amino acid derivatives via allylic amination and [2,3]-sigmatropic rearrangement ' Journal of the American Chemical Society , vol 139 , no. 34 , pp. 11895-11902 . DOI: 10.1021/jacs.7b05619
Journal of the American Chemical Society
Copyright © 2017 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
DescriptionThe research leading to these results (S.S.M.S.) has received funding from the European Union (Marie Curie ITN “SubiCat” PITN-GA-2013-607044) and the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/E.R.C. grant agreement no 279850 (T.H.W., J.E.T.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.
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