A Mixed Naphthyl-Phenyl Phosphine Ligand Motif for Suzuki, Heck, and Hydrodehalogenation Reactions

Abstract

Nap-Phos, representing a new naphthyl-phenyl biaryl-type phosphine ligand class and available by a short synthesis (4 steps, 71% overall yield), effectively catalyzes the Suzuki-Miyaura (including highly hindered cases), hydrodehalogenation, and Heck reactions.

Key words

cross-coupling - Suzuki-Miyaura - homogenous catalysis - Heck reaction - phosphorus ligand - hindered biaryls - dehydrohalogenation

References and Notes

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  Replacement of (EtO)₃SiH with the more economical and non-toxic polyhydromethylsiloxane (PMHS), as suggested in the above reference, was similarly effective (110 °C, 56 h) but caused problems of incomplete separation of polymeric siloxanes in column chromatography.

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13

As established by X-ray single crystal (Figure [2] ) and NMR analysis, compound 4 shows strong intra- and intermolecular hydrogen bonds in the solid state and in solution. The (C1)O-H-O=P intramolecular bond distances are 1.079 Å and 1.533 Å, respectively, while intermolecular (C4′)O-H-O=P bond distances are 1.046 Å and 1.794 Å, respectively. The ³¹P NMR spectrum reveals a low field shifted phosphorus signal at δ = 67.9 ppm and the ¹H NMR spectrum (anhyd DMSO-d ₆) exhibits two widely separated signals for the hydroxyl hydrogens at δ = 13.66 ppm and δ = 7.95 ppm confirming the presence of only one intramolecular (C1)OH-O=P hydrogen bond. A similar phenomenon was observed in benzene-d ₆ solution.
Crystallographic data (excluding structure factors) for the structure of 4 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-609270. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK [fax: [phone]; e-mail: [e-mail]).

17

Use of an equimolar ligand 7:Pd(OAc)₂ ratio produced a very active catalyst, leading to 50% product formation in 15 min in DMF or MeOH at 40 °C (Table [1] , entry 1).

23

For hindered examples, Table [1] , entry 2: S-phos (93%), [6a] Nap-Phos: (98%); entry 3: S-phos (82%), [6a] Nap-Phos: (76%); entry 4: S-phos (86%), [6a] Nap-Phos (70%).

24

A preliminary PM3 modeling study shows a low racemization barrier (20 kcal/mol) for Nap-Phos which precludes its use as a chiral ligand in cross coupling reactions under conditions described herein. Few chiral non-racemic atropisomeric ligand motifs are known. For discussion, see ref. 14c.