Synthesis of Copper(I) Complexes Containing Enantiopure Pybox Ligands. First Assays on Enantioselective Synthesis of Propargylamines Catalyzed by Isolated Copper(I) Complexes

Abstract

Dinuclear [Cu(2)(R-pybox)(2)][X](2) [X = PF(6), R-pybox = 2,6-bis[4'-(S)-isopropyloxazolin-2'-yl]pyridine (S,S)-(i)Pr-pybox (1), 2,6-bis[4'-(R)-phenyloxazolin-2'-yl]pyridine) (R,R)-Ph-pybox (2), 2,6-bis[4'-(S)-isopropyl-5',5'-difeniloxazolin-2'-yl]pyridine (S,S)-(i)Pr-pybox-diPh (3); X = OTf, (R,R)-Ph-pybox (4)] and mononuclear complexes [Cu(R-pybox)(2)][PF(6)] [R-pybox = (S,S)-(i)Pr-pybox (5), (R,R)-Ph-pybox (6)] have been diastereoselectively prepared by reaction of [Cu(MeCN)(4)][PF(6)] or CuOTf.0.5C(6)H(6) and the corresponding pybox ligand. The reaction of CuX (X = I, Br, Cl) with substituted pybox in a 2:1 molar ratio allows us to synthesize tetranuclear complexes [Cu(4)X(4)(R-pybox}(2)] [R-pybox = (S,S)-(i)Pr-pybox, X = I (7), Br (8); (R,R)-Ph-pybox, X = I (9), Br (10), Cl (11); (S,S)-(i)Pr-pybox-diPh, X = I (12), Cl (13)]. Dinuclear complexes [Cu(2)(mu-Cl)(R-pybox)(2)][CuCl(2)] [R-pybox = (S,S)-(i)Pr-pybox (15), (R,R)-Ph-pybox (16)] have been prepared by reaction of CuCl with (i)Pr-pybox or Ph-pybox in 3:2 molar ratio. The structures of the complexes 1, 2, 7, 15, 16 and that of the polymeric species [Cu(4)(mu(3)-Br)(3)(mu-Br)((i)Pr-pybox)](n) (14) have been determined by single-crystal X-ray diffraction analysis. Diffusion studies using (1)H and (19)F-DOSY experiments provide evidence that the different nuclearity of compounds 1 and 5 is maintained in the solution state and confirm that these ionic compounds exist in solution as stable, discrete, cationic complexes. The complexes 1-4, 6, 9, 10, and 16 as well as the previously reported [Cu(2){(S,S)-(i)Pr-pybox}(2)][OTf](2) have been assayed as catalysts in the enantioselective synthesis of propargylamines. The dinuclear complexes [Cu(2){(R,R)-Ph-pybox}(2)][X](2) (2, 4) were found to be the most efficient catalysts (up to 89% e.e.).

Reactivity of Dinuclear Copper(I)/pybox Complexes towards Isocyanides and Phosphanes

“…The Cu-Cu distance [2.7430(11) Å] is consistent with nonbonding Cu-Cu contacts [14] and is similar to that found for the precursor 1 [2.7292(12) Å]. [5] Remarkably, the pybox skeleton is not planar with a torsion angle [N(2)-C(7)-C(6)-N(1)] of 31.2(10)°. The Cu-P distance is 2.2776 Å on average, which is comparable to those observed in other dinuclear copper(I) complexes containing μ-dppm ligands.…”

“…While the former anionic ligand produced [5] the dinuclear complex [Cu 2 (μ-Cl){(S,S)-iPr-pybox} 2 ][PF 6 ], the latter ligand gave a complex mixture from which only [Cu(CϵCPh)] n could be characterized. At this point, we turned our attention to the behavior of complexes 1 and 2 towards neutral ligands.…”

“…From this spectroscopic information it can be deduced that: (i) the rapid pyridine ligand exchange, which makes both of the oxazoline rings of the one pybox ligand equivalent at room temperature, is frozen at 193 K and (ii) at this temperature there is still a symmetry element in the molecule that preserves the equivalence between one half of a pybox unit and the other half of the second pybox unit and that makes the two isocyanide ligands equivalent. On the other hand, the internal fluxional equilibrium of the precursor complex, [Cu 2 {(S,S)-iPr-pybox) 2 }][PF 6 ] 2 (1), is not frozen when the solution is cooled below 183 K. [5] It can be assumed that the internal fluxional equilibrium may be unfavorable for complex 3, in contrast to complex 1, because of the less stable conformation that is imposed by the higher coordination number of the copper atoms. pybox)(PRPh 2 ) 2 ][PF 6 ] (7-9) in good yield (75-76 %) (Scheme 2).…”

“…[5] The dinuclear structure of these derivatives was confirmed in the solid state and in solution by X-ray diffraction studies and by 1 H and 19 F DOSY NMR spectroscopy, respectively. We proposed that [Cu 2 (R-pybox) 2 ][X] 2 complexes, which contain two equivalent tricoordinate copper centers in the solution state, are the active catalytic species, although the mononuclear species resulting from the dissociation of the former complexes during the catalytic cycle could not be definitively ruled out.…”

Construction of Chiral Tri‐ and Tetra‐Arylmethanes Bearing Quaternary Carbon Centers: Copper‐Catalyzed Enantioselective Propargylation of Indoles with Propargylic Esters

“…To obtain more information on the reactive species of the real copper catalyst, we prepared the copper-pybox complex [Cu 2 (L1) 2 (m-Cl)][CuCl 2 ] [13,14] (4) from the reaction of CuCl with 0.7 equivalents of L1 in acetone at room temperature for 24 hours (Scheme 1 a). The molecular structure of 4 was unambiguously characterized by X-ray crystallography, and an ORTEP drawing of the cationic part of 4 is shown in A proposal of the dicopper complex, such as 4, as a reactive species in the present propargylation is also supported by a nonlinear relationship [15] between the ee value of optically active ligand L1 and the ee value of 3 a, which is produced by treatment of 1 a with 2 a in methanol at 0 8C for 48 hours in the presence of 5 mol % of CuOTf·1/2 C 6 H 6 and 10 mol % of L1 as shown in Scheme 1 c. This result provides direct evidence that a dinuclear copper complex works as a key reactive species in the propargylation.…”