Pd-PEPPSI-IPent: Low-Temperature Negishi Cross-Coupling for the Preparation of Highly Functionalized, Tetra-ortho-Substituted Biaryls-

Reaction Scheme

Abstract

A convenient protocol for the rapid and efficient synthesis of 3-(N-substituted) aminocoumarins is described. The synthetic route developed involves the Pd-catalyzed C-N coupling reaction from readily available 3-bromocoumarin derivatives in the presence of the catalytic system Pd(OAc)2/Xantphos. Under these conditions, a series of nucleophiles including amides, sulfonamides, carbamates and functionalized amines, have been successfully reacted to afford the coupling products in fair to good yields.

Substrates

Procedure

A flame-dried resealable Schlenk tube was charged with Pd(OAc)2 (0.025 mmol, 2.0 mol %), Xantphos (0.025 mmol, 2.0 mol %), the solid reactant(s) (1.0 mmol of the bromocoumarin, 1.2 mmol of the amide/amine/carbamate/sulfonamide) and Cs2CO3 (1.5 mmol). The Schlenk tube was capped with a rubber septum, evacuated and backfilled with argon; this evacuation/backfill sequence was repeated one additional time.? The liquid reactant(s) and 1,4-dioxane (2 mL per mmol) were added through the septum. The septum was replaced with a teflon screwcap. The Schlenk tube was sealed, and the mixture was stirred at 100 �C (reaction time, see Table 2). The resulting suspension was cooled to room temperature and filtered through a pad of Celite eluting with ethyl acetate, and the inorganic salts were removed. The filtrate was concentrated and purification of the residue by silica gel column chromatography gave the desired product

Products

Materials

     
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