Sachie Arae

Kinetic Resolution of Planar-Chiral (η6-Arene)Chromium Complexes by Molybdenum-Catalyzed Asymmetric Ring-Closing Metathesis†

Planar-chiral (h-arene)chromium complexes are useful chiral scaffolds in asymmetric synthesis, and have found widespread application as chiral ligands for asymmetric catalysis, or as chiral building blocks for natural product syntheses. Typical methods for the preparation of enantiomerically enriched planar-chiral (arene)chromium species are based either on the optical resolution of racemates or on stereoselective transformations, which include diastereoselective complexation, diastereoor enantioselective ortho-lithiation by utilizing a chiral directing group or a chiral base, and diastereoor enantioselective nucleophilic addition/hydride abstraction. Whereas these methods require a stoichiometric amount of chiral reagents or auxiliaries, asymmetric catalysis is an attractive and effective alternative for preparing optically active (h-arene)chromium complexes. Since the first report on such a catalytic process by Uemura et al. in 1993, only a handful of examples of the desymmetrization of prochiral (arene)chromium substrates have been reported by Gotov and Schmalz, K ndig and co-workers, and Uemura and co-workers 11] . Recently, we reported the preparation of phosphinechelate (h-arene)chromium complexes by Ru-catalyzed ringclosing metathesis. We also demonstrated that Mo-catalyzed asymmetric ring-closing metathesis (ARCM) was highly effective for the asymmetric synthesis of the various planarchiral ferrocenes. Thus, we are interested in controlling the planar chirality of (h-arene)chromium complexes by ARCM. Indeed, the kinetic resolution of racemic (h1,2-disubstituted benzene)chromium complexes proceeds efficiently in the presence of a chiral Mo-alkylidene species to give the planar-chiral chromium complexes with excellent enantiomeric purity. Furthermore, a highly enantiomerically enriched (h-bromoarene)chromium complex that was prepared by using the present method is an excellent precursor to various planar-chiral (arene)chromium derivatives. A (phosphinoarene)chromium species was derived from the (hbromoarene)chromium complex and applied as a chiral ligand in Rh-catalyzed asymmetric reactions, which achieved excellent enantioselectivity of up to 99.5%. The (h-arene)chromium complexes (rac-1) that were used in this study contain an h-(2-substituted alkenylbenzene) ligand, which constructs the planar-chiral environment upon coordination to the chromium atom, and an alkenylphosphine ligand. The chiral catalysts were screened by using racemic [(h-2-methylstyrene)Cr(CO)2(methallyldiphenylphosphine)] (1a) as a prototypical substrate. The asymmetric reactions were carried out in benzene at 40 8C in the presence of an appropriate chiral Mo catalyst (10 mol%), which was generated in situ from the Mo precursor [(pyrrolyl)2Mo(= CHCMe2Ph)(=NC6H3-2,6-iPr2)] and an axially chiral biphenol derivative (Table 1). Under these conditions, the Mo catalyst that was generated with (R)-L1 gave the ARCM product 2 a in 32% yield with an ee value of 79 %, and unreacted 1a was recovered in 66% yield with an ee value of 50% (entry 1). The krel value ([reaction rate of the fastreacting enantiomer]/[reaction rate of the slow-reacting enantiomer]; selectivity factor) for this reaction is estimated to be 14. The Mo catalyst that was generated with (R)-L2 gives better enantioselectivity and the krel value improved to 41 (entry 2). Lowering the temperature worsened the selectivity; the krel value was 12 at 23 8C (entry 3). It was found that the reaction with the Mo catalyst coordinated with (S)-L3 shows excellent enantioselectivity; 2a was obtained in 96 % ee and 44 % yield, and 1a was recovered in 88% ee and 50% yield. The krel value for the reaction is 114 (entry 4), and a nearly perfect kinetic resolution of the two enantiomers of rac-1a was achieved. Considering the structural similarity between L1, L2, and L3, these results are quite surprising and indicate that the slight structural modification to the Mo catalysts affects the enantioselectivity of the asymmetric reaction. After the optimization studies, the Mo/(S)-L3 species was applied to the other substrates. The substrate rac-1b, which has an ethyl substituent in place of the ortho-methyl group in 1a, was also resolved as above. The enantioselectivity and the reaction efficiency (krel = 75 (entry 5)) of the kinetic resolution of rac-1b were still high. Substrate 1 c contains an hbromostyrene ligand. As the bromo substituents in 1c/2c can be easily replaced by other functional groups by standard organic transformations (see below), they serve as versatile precursors to various planar-chiral compounds. The reaction of rac-1c under the optimized conditions afforded complex 2c in 97 % ee and 47% yield. Unreacted 1c was also recovered in 89% ee and 50 % yield. The krel value for this reaction is 198 [*] Prof. M. Ogasawara, S. Arae, Dr. S. Watanabe, Prof. T. Takahashi Catalysis Research Center and Graduate School of Life Science Hokkaido University, Kita-ku, Sapporo 001-0021 (Japan) E-mail: ogasawar@cat.hokudai.ac.jp

Phosphine–Olefin Ligands Based on a Planar-Chiral (π-Arene)chromium Scaffold: Design, Synthesis, and Application in Asymmetric Catalysis

The NMR and X-ray crystallographic studies clarified that planar-chiral alkenylene-bridged (phosphino-π-arene)(phosphine)chromium complexes 3 were capable of coordinating to a rhodium(I) cation in a bidentate fashion at the (π-arene)-bound phosphorus atom and at the olefin moiety. The P-olefin chelate coordination of 3 constructs the effective chiral environment at the metal center, and thus, these rhodium complexes display high performances in various rhodium-catalyzed asymmetric 1,4- and 1,2-addition reactions with arylboron nucleophiles. The control experiments demonstrated that the (η(2)-olefin)-Rh interaction as well as the bridging structure in 3 played the pivotal roles in the high enantioselectivity of the Rh-catalyzed asymmetric reactions. To enhance the synthetic utilities of these phosphine-olefin ligands, an enantiospecific and scalable synthetic method was developed. The novel synthetic method is flexible in terms of the substituent variation, and a library of the planar-chiral (arene)chromium-based phosphine-olefin ligands was established by the combinatorial approach. Among the newly prepared ligand library, compound 3g, which is with a bis(3,5-dimethylphenyl)phosphino group on the η(6)-arene ring, was found to be a far better chiral ligand in the rhodium-catalyzed asymmetric reactions showing excellent enantioselectivity and high yields.

Kinetic Resolution of Planar-Chiral 1,2-Disubstituted Ferrocenes by Molybdenum-Catalyzed Asymmetric Intraannular Ring-Closing Metathesis

Planar chirality: Ring-closing metathesis of 1,2-diallylmetallocenes afforded the corresponding 4,7-dihydroindenyl species in high yields. The metallocenes are planar chiral with two different allylic substituents, and kinetic resolution of the racemic 1,2-diallylmetallocene derivatives was realized by molybdenum-catalyzed asymmetric ring-closing metathesis with excellent enantioselectivity (see scheme).

Simultaneous Induction of Axial and Planar Chirality in Arene–Chromium Complexes by Molybdenum‐Catalyzed Enantioselective Ring‐Closing Metathesis

The molybdenum-catalyzed asymmetric ring-closing metathesis of the various Cs -symmetric (π-arene)chromium substrates provides the corresponding bridged planar-chiral (π-arene)chromium complexes in excellent yields with up to >99 % ee. With a bulky and unsymmetrical substituent, such as N-indolyl or 1-naphthyl, at the 2-positions of the η(6) -1,3-diisopropenylbenzene ligands, both biaryl-based axial chirality and π-arene-based planar chirality are simultaneously induced in the products. The axial chirality is retained even after the removal of the dicarbonylchromium fragment, and the chiral biaryl/heterobiaryl compounds are obtained with complete retention of the enantiopurity.

Enantioselective synthesis of macrocyclic heterobiaryl derivatives of molecular asymmetry by molybdenum-catalyzed asymmetric ring-closing metathesis

Winding vine-shaped molecular asymmetry is induced by enantioselective ring-closing metathesis with a chiral molybdenum catalyst. The reaction proceeds under mild conditions through an E-selective ring-closing metathesis leading to macrocyclic bisazoles with enantioselectivities of up to 96% ee.