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. 2020 Feb 7;22(3):976-980.
doi: 10.1021/acs.orglett.9b04506. Epub 2020 Jan 27.

Redox-Annulations of Cyclic Amines with ortho-Cyanomethylbenzaldehydes

Anirudra Paul  1   2 , Hemant S Chandak  2 , Longle Ma  2 , Daniel Seidel  1   2
Affiliations

Redox-Annulations of Cyclic Amines with ortho-Cyanomethylbenzaldehydes

Anirudra Paul et al. Org Lett. .

Abstract

Amines such as 1,2,3,4-tetrahydroisoquinoline undergo redox-neutral annulations with ortho-cyanomethylbenzaldehydes. These amine α-C-H bond functionalization reactions are promoted by acetic acid. The resulting β-aminonitriles can be converted to the corresponding β-aminoalcohols in diastereoselective fashion.

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Figures

Scheme 1.
Scheme 1.
Selected Redox-Annulations of Amines
Scheme 2.
Scheme 2.
Scope of the aldehydea a Reactions were performed on a 0.5 mmol scale. All yields correspond to isolated yields.b Performed on a 1 mmol scale.
Scheme 3.
Scheme 3.
Scope of the aminea a Reactions were performed on a 0.5 mmol scale. All yields correspond to isolated yields.b Two equiv of the amine were used.
Scheme 4.
Scheme 4.
Decarboxylative annulationsa a Reactions were performed on a 0.5 mmol scale. All yields correspond to isolated yields.
Scheme 5.
Scheme 5.
Equilibration of product diastereomers a AcOH (20 equiv), 1,2-dichloroethane, reflux, 4 h.
Scheme 6.
Scheme 6.
Unexpected product modification
See this image and copyright information in PMC

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