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. 2022 Jun 3;24(21):3812-3816.
doi: 10.1021/acs.orglett.2c01355. Epub 2022 May 23.

Pd-Catalyzed Dynamic Kinetic Asymmetric Cross-Coupling of Heterobiaryl Bromides with N-Tosylhydrazones

Shivashankar Kattela  1 , Carlos Roque D Correia  2 , Abel Ros  1 , Valentín Hornillos  1   3 , Javier Iglesias-Sigüenza  3 , Rosario Fernández  3 , José M Lassaletta  1
Affiliations

Pd-Catalyzed Dynamic Kinetic Asymmetric Cross-Coupling of Heterobiaryl Bromides with N-Tosylhydrazones

Shivashankar Kattela et al. Org Lett. .

Abstract

A dynamic kinetic asymmetric Pd-catalyzed cross-coupling reaction of heterobiaryl bromides with ketone N-tosylhydrazones for the synthesis of heterobiaryl styrenes is described. The combination of Pd(dba)2 as a precatalyst with a TADDOL-derived phosphoramidite ligand provides the corresponding coupling products in good yields and high enantioselectivities under mild conditions. Racemization-free N-oxidation and N-alkylation of the products allowed us to obtain appealing functionalized axially chiral heterobiaryl derivatives.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Antecedents and Our Synthetic Plan
Scheme 2
Scheme 2. Scope of Hydrazones and Heterobiaryls
Reaction conditions: 0.1 mmol of 1A–D in anhydrous 1,4-dioxane (1.2 mL), 2a–k (0.15 mmol, 1.5 equiv), and 3 equiv of LiOtBu for 24 h at 60 °C. Yields given for isolated products after chromatographic purification. The ee values were determined by HPLC on chiral stationary phases. Reaction performed on a 1.5 mmol (536 mg) scale. Absolute configuration determined by X-ray single-crystal analysis.
Scheme 3
Scheme 3. Representative Derivatizations
See this image and copyright information in PMC

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