Asymmetric ferrocenyl ligands

Asymmetric ferrocenyl ligands bearing different donor atoms connected through a chiral carbon atom have been used by many groups for different enantioselective reactions. Diferrocenyl dichalcogenides 107-109 were synthesized by Uemura et al. and tested in the ATH of acetophenone in the presence of [lr(cod)Cl]2 in PrOH/NaOH to give (Rj-phenylethan-l-ol at moderate conversions and enanh-oselechvities (Scheme 4.49) [95]. 

Menthone and camphor undergo asymmetric hydrosilylation to give alkoxysilanes with up to 82% optical purity using neutral rhodium(I) catalysts containing DIOP or neomenthyl- or menthyl-diphenylphos-phine even triphenylphosphine gave about 65% ee (300). Hydrolysis to alcohols was not reported. The ferrocenyl ligands (28, 29) are similarly effective for asymmetric hydrosilylation (255), and could be used for production of the optically active alcohols. 

Aminocarbonylation has also been applied to the synthesis of unsymmetrical ferrocene-1,1 -bis-carboxamides. Ferrocene-based chiral ligands are very useful in asymmetric catalysis, and enantiomerically pure ferrocenyl ligands can be obtained by optical resolution of unsymmetrically substituted ferrocenes. However, the synthesis of such unsymmetrical ferrocenes is not an easy task. The use of aminocarbonylation gave a solution to this challenge. For example, the Pd-catalyzed reaction of symmetrical ferrocenyl diiodide 144 with two different amines, morpholine and diethylamine (5 equiv. each) under 39.5 atm of CO, gave the desired unsymmetrically disubstituted ferrocene-biscarboxamide 145 in 85% yield (Equation (11)). ... 

Schwink, L. and Knochel, P. Enantioselective Preparation of C2-Symmetrical Ferrocenyl Ligands for Asymmetric Catalysis. Chem. Eur. J. 1998, 4, 950-968. 

Ferrocenyl ligands, via zinc reagents, 9, 120 Ferrocenylmethyl phosphonium salts, with gold(I), 2, 274 Ferrocenylmonophosphine, in styrene asymmetric hydrosilylation, 10, 817 Ferrocenyl oxazolines, synthesis, 6, 202 Ferrocenylphosphines with chromium carbonyls, 5, 219 in 1,3-diene asymmetric hydrosilylation, 10, 824-826 preparation, 6, 197 various complexes, 6, 201 Ferrocenylselenolates, preparation, 6, 188 Ferrocenyl-substituted anthracenes, preparation, 6, 189 Ferrocenyl terpyridyl compounds, phenyl-spaced, preparation 6, 188 Ferrocifens... 

Togni, A. (1996) Developing new chiral ferrocenyl ligands for asymmetric catalysis. A personal account. Chimia,... 

A. Togni in New Chiral Ferrocenyl Ligands for Asymmetric Catalysis in Metallocenes. Synthesis, Reactivity, Applications , eds. A. Togni and R. L. Halterman, Weinheim, 1998, Vol. 2, p. 685. 

Excellent enantioselectivity and double-bond regioselectivity can be achieved in an asymmetric Heck reaction between 2,3-dihydrofuran and aryl triflates by using a combination of chiral diphosphine-oxazoline ferrocenyl ligand and Pd catalyst <03CEJ3073>, as shown below. Chiral diphosphine-containing (arene)tricarbonylchromium(O) complexes were also used as ligands for this reaction to obtain the 2,3-isomer, however, both the yield and enantioselectivity were modest <03TA1455>. 

Togni, A. Dorta, R. Kollner, C. Pioda, G. Some New Aspects of Asymmetric Catalysis with Chiral Ferrocenyl Ligands, Pure Appl. Chem. 1998, 70,1477-1485. 

Phosphines ligands that have chirality from ferrocenes have been implemented in the iridium-catalyzed asymmetric hydrogenation of imine with moderate enantioselectivities for Novartis s manufacture of metolachlor. Electronic modifications of these ferrocenyl ligands have increased the enantioselectivity and catalyst reactivity for Lonza s asymmetric hydrogenation processes of biotin and 2-substituted piperazines, intermediates for several pharmaceutical drugs. 

More recently, a rran.y-chelating asymmetric ferrocenyl phosphine (abbreviated as TRAP) has been developed [63]. The rhodium complex of TRAP catalyzes asymmetric Michael additions of a-cyanocarboxylates in high enantioselectivity (72-89 % ee) (eq (18)) [64]. Because these Michael reactions proceed via a A -bound enolato complex [65], the reaction center on the enolato ligand is far from the metal center. Thus, a CLv-chelating phosphine cannot control the direction of electrophilic attack. The reaction with c/.y-chelating phosphines gives only a poor enantiomeric excess (BINAP, 17 % ee DIOP, 12 % ee CHIRAPHOS, 3 % ee). 

For an outstanding example of a ferrocenyl ligand in asymmetric catalysis, see Blaser H-U (2002) Adv Syntb Catal 344 17 (and cited literature)... 

Tu, T., Deng, W.-R, Hou, X.-L. et al. (2003) The regioselectivity of the asymmetric intermolecular Heck reaction with planar chiral diphosphine-oxazoline ferrocenyl ligands. Chem. Eur. J., 9, 3073 1. 

For a representative review, see Kagan, H.B., Diter, R, Gref, A., et al. (1996) Towards new ferrocenyl ligands for asymmetric catalysis. PureAppl. Chem., 68, 29-36, and references cited therein. 

Enantioselective 1,3-dipolar cycloaddition of imino esters to electron-deficient alkenes is one of the most powerful and atom-economical C-C bond-forming reaction that facilitates the synthesis of a range of structurally and stereochemically rich pyrrolidines [35]. Wang developed the asymmetric 1,3-dipolar cycloaddition of naphthalene-1,4-dione (116) with imino esters 117 catalyzed by the Cu(I) complex of ferrocenyl ligand 115, followed by silica-gel-promoted aromatization [39]. 

Investigation of the production of planar chiral ferrocene derivatives of use in catalytic asymmetric chemistry has led to the lithiation of N,AI-dimethylferrocenylmethylamine in the presence of non-stoichiometric levels of the chiral diamine tmcda (20% wrt ferrocenyl ligand). Data suggest the ability of this ligand to promote catalytic stereoselective ortho lithiation through the facile ability of Et20 to replace the chiral auxiliary as the lithiate converts from tmcda-complexed monomer to Et20-complexed dimer with retention of stereochemistry. ... 

Rhodium complexes with the ferrocenyl ligand (i ,5)-Cy2PF-PPh2 (109) have been shown to catalyse asymmetric hydroalkynylation of norbornadienes with <99.9% ee A hydroxorhodium complex with (R)-Segphos (110) has been shown to catalyse the hydroarylation of 3-pyrrolines (111) with arylboroxines (112) under neutral conditions to give 3-arylpyrrolidines (113) (<96% ee) ... 

Ireland T, Grossheimann G, Wieser-Jeunesse C, Knochel P (1999) Ferrocenyl ligands with two phosphanyl substituents in the alpha, epsilon positions for the transition metal catalyzed asymmetric hydrogenation of functionalized double bonds. Angew Chem Int Ed 38 3212-3215... 

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