Function of an N-Heterocyclic Carbene Ligand Based on Concept of Chiral Mimetic

Abstract

We have been developing a novel chiral phosphine ligand 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). [1][2][3][4][5][6] In order to expand the scope of our chiral mimetic concept, we planned to develop a novel N-heterocyclic carbene ligand 7-9) 3. The substituent R on the sp 2 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 2 N group is fixed, is expected to be selectively formed (Fig. 2).10) Herein we would like to report our investigations 5) 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 1998.11) The corresponding diarylmethanols were obtained in good yields, and with as a chiral ligand, a product with 41% ee was formed in enantioselective Rh-catalyzed phenylation 4,6,[13][14][15][16][17] of 1-naphthaldehyde 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). 14)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 RhCl 3 · 3H 2 O in DME/H 2 O (5 : 1) according to Fürstner's procedure 18) (entries 1-4). Among the imidazolium salts screened, 9c possessing a t-butyl group as R substituent gave 20% enantioselectivity. The use of toluene/H 2 O (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(CH 2 ϭ CH 2 ) 2 ] 2 as a Rh source was chosen from the viewpoint of Function of a new N-heterocyclic carbene ligand based on the concept of a chiral mimetic is described. With (4R,5R)-4,5-diphenyl-1,3-dialkyl-4,5-dihydro-3H-imidazol-1-ium tetrafluoroborates as N-heterocyclic

Asymmetric Construction of Quaternary Carbon Stereocenter by Pd-Catalyzed Intramolecular .ALPHA.-Arylation

“…[1][2][3][4][5][6] We have been quite recently developing a novel N-heterocyclic carbene ligand 7,8) 1 based on the concept of chiral mimetic. [7][8][9][10][11][12][13] The N-heterocyclic carbene ligand 1 has been found to construct quaternary carbon streocenters with up to 65% enantioselectivity in Pd-catalyzed enantioselective intramolecular a-arylation of N-(2-bromophenyl)-N-methyl-2-arylpropanamide 2 (Chart 1). The enantioselectivity obtained is, to the best of our knowledge, the high level in the reported literature, 14,15) although the chemical yield is moderate.…”

Bulky Chiral Carbene Ligands and Their Application in the Palladium‐Catalyzed Asymmetric Intramolecular α‐Arylation of Amides

“…As an application we chose the palladium-catalyzed asymmetric intramolecular a-arylation of amides because chiral oxindole products are of synthetic interest and because the literature precedents for this reaction showed that there was room for improvement in asymmetric induction. [4][5][6] Herein we report the first results of our studies.…”

“…As an application we chose the palladium-catalyzed asymmetric intramolecular a-arylation of amides because chiral oxindole products are of synthetic interest and because the literature precedents for this reaction showed that there was room for improvement in asymmetric induction.[4-6] Herein we report the first results of our studies.Oxindole alkaloids containing a quaternary benzylic center belong to a large family of natural products that exhibit a variety of significant biological activities, making them interesting and challenging targets for chemical synthesis.[7] Asymmetric transition-metal-catalyzed reactions that provide access to enantiomerically enriched 3-alkyl-3-aryl oxindoles are scarce: Overman and co-workers elegant intramolecular Heck reactions, [8] palladium-catalyzed allylation of 3-arylindoles, [9] and the palladium-catalyzed intramolecular a-arylation of amides, [4][5][6] which are the focus of the present study.Hartwig and Lee tested nineteen mono-and bidentate chiral phosphorous ligands and three in-situ-generated chiral carbene ligands in this reaction, and showed the carbenes outperformed the phosphines.[4] As an example, the best result for the asymmetric cyclization of amide 1 is shown in Scheme 1 together with the results of subsequent reports on this reaction. [5,6] …”

Synthesis of New Chiral Benzimidazolylidene–Rh Complexes and Their Application in Asymmetric Addition Reactions of Organoboronic Acids to Aldehydes

“…Since then, considerable efforts have been made in this type of reaction [23][24][25][26][27][28][29][30]. However, examples of using chiral N-heterocycliccarbenes in the ligand-catalyzed asymmetric arylation of aldehydes are rare [31][32][33][34][35]. Therefore, developing new chiral N-heterocycliccarbene ligands for the asymmetric 1,2-addition of arylation of aldehydes are rare [31][32][33][34][35].…”

“…However, examples of using chiral N-heterocycliccarbenes in the ligand-catalyzed asymmetric arylation of aldehydes are rare [31][32][33][34][35]. Therefore, developing new chiral N-heterocycliccarbene ligands for the asymmetric 1,2-addition of arylation of aldehydes are rare [31][32][33][34][35]. Therefore, developing new chiral N-heterocycliccarbene ligands for the asymmetric 1,2-addition of organoboronic acid to aldehydes is an important synthetic goal.…”