Chem. Pharm. Bull. 54(11) 1576—1581 (2006)

1 mimicking axial chirality, in which a chiral carbon center induces a preferred conformation 2a by rotation around an N–Ar bond which is fixed by formation of a chelate structure with metal (Fig. 1). In order to expand the scope of our chiral mimetic concept, we planned to develop a novel N-heterocyclic carbene ligand 3. The substituent R on the sp N group in the carbene ligand 3 may be conformationally flexible, but if the complexation of 3 and metal is reflected by the asymmetric center in 3, a more stable complex 4a, in which the substituent R on the sp N group is fixed, is expected to be selectively formed (Fig. 2). Herein we would like to report our investigations on Rh-catalyzed enantioselective arylation of aromatic aldehydes 5 with arylboronic acids and enantioselective intramolecular a-arylation of amides 7 with the novel N-heterocyclic carbene (NHC) ligand 3 (Chart 1). Rh-Catalyzed Enantioselective Arylation of Aromatic Aldehydes with Arylboronic Acids Rh-catalyzed arylation of aromatic aldehydes with arylboronic acids was reported by Miyaura in 1998. The corresponding diarylmethanols were obtained in good yields, and with MeOMOP as a chiral ligand, a product with 41% ee was formed in enantioselective Rh-catalyzed phenylation of 1naphthaldehyde with PhB(OH)2. A recent attempt by Bolm using planar chiral imidazolium salts as NHC ligand precursors attained moderate enantioselectivity (up to 38% ee). Bolm’s results using NHC ligands prompted us to investigate the applicability of NHCs to the rather unexplored enantioselective arylation of aromatic aldehyde with arylboronic acids. We began to screen imidazolium salts as NHC ligand precursors 9a—d in enantioselective phenylation of 1-naphthaldehyde (5a) with PhB(OH)2 (14a). The results are shown in Table 1. At first, reactions were carried out with the use of RhCl3· 3H2O in DME/H2O (5 : 1) according to Fürstner’s procedure (entries 1—4). Among the imidazolium salts screened, 9c possessing a t-butyl group as R substituent gave 20% enantioselectivity. The use of toluene/H2O (5 : 1) as solvent gave the same results. In place of NaOt-Bu, KOt-Bu, LiOt-Bu and LiOH gave same results, and use of KHMDS and NaHMDS decreased reaction rates but ee’s were unaffected. With 9c, further screening (entries 5, 6) of other rhodium complexes was perforemed, and [RhCl(CH2 CH2)2]2 as a Rh source was chosen from the viewpoint of 1576 Vol. 54, No. 11 Chem. Pharm. Bull. 54(11) 1576—1581 (2006)