Assessment of the regioselectivity in the condensation reaction of unsymmetrical o-phthaldialdehydes with alanine
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One approach for the synthesis of isoindolinones, a privileged bioactive heterocyclic core structure, involves a condensation reaction of o-phthaldialdehydes with a suitable nitrogen-containing nucleophile. This fascinating reaction is revisited here in the context of the use of o-phthaldialdehydes that contain additional substituents in the aromatic ring leading to a detailed analysis of the regioselectivity of the reaction. Eleven monosubstituted o-phthaldialdehydes were synthesised and reacted with alanine. The regioselectivity observed across the eleven substrates led to the design of a disubstituted substrate that reacted with very high control. A gram-scale reaction followed by esterification gave one major regioisomer in high yield. In addition, the regioselectivity observed on reaction of two novel monodeuterated substrates led to an increased mechanistic understanding.
D'Hollander , A C A & Westwood , N J 2018 , ' Assessment of the regioselectivity in the condensation reaction of unsymmetrical o -phthaldialdehydes with alanine ' , Tetrahedron , vol. 74 , no. 2 , pp. 224-239 . https://doi.org/10.1016/j.tet.2017.11.035
© 2017 Elsevier Ltd. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1016/j.tet.2017.11.035
DescriptionFunding: We would like to thank the EPSRC DTG at the University of St Andrews for funding.
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