Synthesis and resolution of 2-(2-diphenylphosphinyl-naphthalen-1-yl)-1-isopropyl-1H-benzoimidazole; a new atropisomeric P,N-chelating ligand for asymmetric catalysis

doi:10.1016/S0957-4166(02)00079-4

Tetrahedron: Asymmetry

Volume 13, Issue 2, 28 February 2002, Pages 137-144

https://doi.org/10.1016/S0957-4166(02)00079-4 Get rights and content

Abstract

A multistep synthesis resulting in a good yield of the title compound 13 (BIMNAP) has been developed based on N,N-acetal-formation and oxidation with MnO₂. The product 11 is converted into the corresponding trifluoromethane sulfonate 12 by treatment with (CF₃SO₂)₂O followed by a nickel-catalysed coupling-reaction with HPPh₂. Resolution of the phosphanamine 13 was carried out via fractional crystallisation of the diastereomeric hexafluorophosphate salts of the Pd-complex 15, formed from reaction of 13 with (+)-di-μ-chlorobis{2-[1-(dimethylamino)ethyl]phenyl-C,N}dipalladium (S)-14. The absolute configurations of the two diastereomers were determined by X-ray crystallography.

Graphic

Introduction

Of the many types of ligands which could be used for catalytic asymmetric reactions, chiral tertiary phosphines have been established as the most effective for homogeneous transition metal catalysis.1., 2. Due to the success of the DIOP-ligand developed by Kagan, C₂-symmetric bisphosphine ligands dominated asymmetric catalysis for a long time.³ One of the most effective chiral bisphosphine ligands proved to be atropisomeric BINAP,⁴ which was introduced by Noyori in the early 1980s and has proved highly successful in many asymmetric reactions including the synthetically important rhodium- and ruthenium-catalysed hydrogenation, hydroboration and hydroformylation protocols (Fig. 1).

Subsequently, some monophosphine systems bearing an additional donor atom have been shown to be very effective ligands for chiral catalysis. Besides O-P-ligands, their N-P counterparts have attracted great interest. These include not only atropisomers like QUINAP 1 and PHENAP 2, which have been used successfully in the rhodium-catalysed hydroboration of styrene and palladium-catalysed allylic substitution reaction,5., 5.(a), 5.(b), 5.(c), 5.(d), 6. but also simple phosphinooxazoline ligands 3 which were introduced by Helmchen,⁷ Pfaltz⁸ and Williams.⁹ Phosphinoxazoline ligands induce excellent enantio-selectivities in palladium-catalysed allylic alkylations with 1,3-diphenylallyl acetate and other symmetrically substituted allyl derivatives. We wondered if related P-N-systems of the type 4 could be developed, which by proper choice of R group could lead to atropisomers sufficiently stable to be resolved and used as chiral ligands in asymmetric synthesis.

Section snippets

Ligand preparation

The synthesis of the new ligand 13 started with N,N-acetal formation of the diamine 7 and the aldehyde 9 to give the 2,3-dihydro-1H-benzoimidazole 10 followed by oxidation to the 1H-benzoimidazole system 11 (Scheme 1).

The diamine 7 could be prepared easily from 2-nitrophenylamine 5 by reductive amination with acetone/BH₃·SMe₂¹⁰ to give 6 in 92% yield followed by reduction of the nitro-group with H₂ over Pd/C in EtOH (98% yield).10., 11. Heating 7 and the commercially available aldehyde 9 for 2

Ligand resolution

The resolution of bidentate P,N-ligands has been widely studied and ortho-palladated derivatives of (S)-dimethyl(1-phenylethyl)amine have proved to be useful resolving agents.13., 13.(a), 13.(b) The phosphinamine 13 and (S)-14 were stirred in methanol for 2 h; on addition of KPF₆ the diastereomeric products (S,R_a)-15 and (S,S_a)-15 precipitated and could be isolated after filtration as a pale yellow solid, which was shown by ¹H NMR to consist of a 1:1 mixture of diastereomers (Scheme 2).

The key

Apparatus and materials

NMR spectra were recorded on a Bruker ARX 400 spectrometer. ¹H and ¹³C chemical shifts are reported in δ ppm relative to the used deuterosolvent. ³¹P chemical shifts are reported relative to 85% aqueous phosphoric acid (0 ppm). Mass spectra were recorded on a Varian MAT 311A. EI-HR-MS were recorded on a MAT 95 (Fa. Finnigan), ESI-HR-MS on a LCT (Fa. Micro Mass). IR spectra were recorded on a Nicolet Avatar 360 FT spectrometer. Optical rotations were recorded on a Perkin–Elmer 241 polarimeter.

Acknowledgements

We would like to thank Dr. Swen Allerheiligen from the Bayer AG Wuppertal for measurement of the HRMS spectra.

References (15)

N. Alcock et al.
Tetrahedron: Asymmetry
(1993)
A. Pfaltz
Acta Chem. Scand. B
(1996)
J. Williams
Synlett
(1996)
T. Hayashi
Acc. Chem. Res.
(2000)
E. Jacobsen et al.
(1999)
J. Whitesell
Chem. Rev.
(1989)
R. Noyori et al.
Acc. Chem. Res.
(1990)

There are more references available in the full text version of this article.

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