Pd(II)-Catalyzed, Picolinamide-Aided γ-(sp2)-C–H Functionalization of Racemic and Enantiopure α-Methylbenzylamine and Phenylglycinol Scaffolds

Narendra Bisht; Prabhakar Singh; Srinivasarao Arulananda Babu

doi:10.1055/a-1830-3962

Synthesis, Table of Contents

Synthesis 2022; 54(18): 4059-4094
DOI: 10.1055/a-1830-3962

paper

Pd(II)-Catalyzed, Picolinamide-Aided γ-(sp²)-C–H Functionalization of Racemic and Enantiopure α-Methylbenzylamine and Phenylglycinol Scaffolds

Narendra Bisht‡

,

Prabhakar Singh‡

,

Srinivasarao Arulananda Babu ∗

Abstract

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Abstract

In this paper, we report the Pd(II)-catalyzed, picolinamide DG-aided sp² γ-C–H functionalization and expansion of the library of enantiopure α-methylbenzylamine and phenylglycinol scaffolds. We have shown the synthesis of a wide range of racemic and enantiopure ortho-C–H arylated, alkylated, brominated, and iodinated α-methylbenzylamine and phenylglycinol scaffolds. Various racemic and R and S (chiral) sp² γ-C–H functionalized α-methylbenzylamine and phenylglycinol scaffolds were synthesized with good enantiopurities. Racemic and enantiopure α-methylbenzylamine and phenylglycinol derivatives are important building blocks in organic synthesis and medicinal chemistry. Accordingly, this work contributes to the expansion of the libraries of α-methylbenzylamine and phenylglycinol motifs and substrate scope development through the Pd(II)-catalyzed bidentate directing group picolinamide-aided site-selective C–H activation and functionalization method.

Key words

amino alcohols - bidentate directing groups - biaryls - C–H functionalization - cross-coupling - α-methylbenzylamine - palladium - stereoselective synthesis

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References

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16 CCDC 2036403 (8h-(RS)) and 2156612 (12e-(RS)) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
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18 While a single signal is expected, there seems to be the existence of rotamers; thus, more than one signal is observed. For a related paper dealing with rotamers with aryl compounds containing F, see: Sun M, Chen W, Zhang T, Liu Z, Wei J, Xi N. Tetrahedron 2020; 76: 131679

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