The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1 H-isoindolin-1-ones

Ommid Anamimoghadam; Saira Mumtaz; Anke Nietsch; Gaetano Saya; Cherie A Motti; Jun Wang; Peter C Junk; Ashfaq Mahmood Qureshi; Michael Oelgemöller

doi:10.3762/bjoc.13.275

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1 H-isoindolin-1-ones

Beilstein J Org Chem. 2017 Dec 20:13:2833-2841. doi: 10.3762/bjoc.13.275. eCollection 2017.

Authors

Ommid Anamimoghadam¹, Saira Mumtaz¹, Anke Nietsch², Gaetano Saya¹, Cherie A Motti³, Jun Wang¹, Peter C Junk¹, Ashfaq Mahmood Qureshi⁴, Michael Oelgemöller¹

Affiliations

¹ James Cook University, College of Science and Engineering, Townsville, Queensland 4811, Australia.
² Dublin City University, School of Chemical Sciences, Dublin 9, Ireland.
³ Australian Institute of Marine Science, Townsville, Queensland, Australia.
⁴ Bahauddin Zakariya University, Institute of Chemical Sciences, Multan, Pakistan.

Abstract

The synthesis of various 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones was realized following a simple three-step process. The protocol utilized the photodecarboxylative addition of readily available carboxylates to N-(bromoalkyl)phthalimides as a versatile and efficient key step. The initially obtained hydroxyphthalimidines were readily converted to the desired N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones via acid-catalyzed dehydration and subsequent nucleophilic substitution with the corresponding secondary amines. The procedure was successfully applied to the synthesis of known local anesthetics (AL-12, AL-12B and AL-5) in their neutral forms.

Keywords: anesthetics; arylmethylenedihydroisoindolinones; photochemistry; photodecarboxylation; phthalimide.