Planar Chiral Ferrocene ligands

My personal interest in asymmetric catalysis can be dated back to my graduate study under the supervision with Professor Li-Xin Dai at the Shanghai Institute of Organic Chemistry, where my Ph.D. thesis had been focused on the synthesis of (planar) chiral ferrocene ligands and their application in Pd-catalyzed allylic substitution reactions. Since my independent research was started in 2006, our group has been focusing on asymmetric direct functionalization reactions of various C—H bonds, including Pd-catalyzed... 

Abstract Chiral ferrocenyl phosphine ligands are certainly one of the most developed and successful classes of chiral ligands used in asymmetric catalysis. The literature describing their synthetic and coordination chemistry, as well as their metal-mediated applications in the field of catalysis, is extremely rich and varied. Moreover, they represent a rare example in which enantioselective chemical catalysts were used in industrial processes. The present chapter provides an account of the planar-chiral ferrocene ligands developed in the Authors laboratory, including their coordination chemistry with various metals as well as their use in different asymmetric catalytic reactions (allylic substitution, Suzuki coupling, methoxycarbonylation of alkenes, hydrogenation of ketones). 

Fu has reported a planar-chiral bisphosphorus ligand 45 with a phosphaferrocene backbone. The ligand has provided enantioselectivity up to 96% ee in the hydrogenation of a-dehydroamino acid derivatives.99 Another planar-chiral ferrocene-based bisphosphorus ligand 46 has been reported by Kagan recently and enantioselectivity up to 95% ee has been obtained in the reduction of dimethyl itaconate.100... 

While Josiphos 41 also possessed an element of atom-centered chirality in the side chain, Reetz reported a new class of ferrocene-derived diphosphines which had planar chirality only ligands 42 and 43, which have C2- and C -symmetry, respectively.87 Rhodium(i)-complexes of ligands (—)-42 and (—)-43 were used in situ as catalysts (0.75 mol%) for the hydroboration of styrene with catecholborane 1 for 12 h in toluene at — 50 °C. The rhodium/ i-symmetric (—)-43 catalyst system was the more enantioselective of the two - ( -l-phenylethanol was afforded with 52% and 77% ee with diphosphines (—)-42 and (—)-43, respectively. In both cases, the regioselectivity was excellent (>99 1). With the same reaction time but using DME as solvent at lower temperature (—60 °C), the rhodium complex of 43 afforded the alcohol product with an optimum 84% ee. 

Despite the resolution which was required to produce the enantiomerically pure starting materials (which fortunately is highly efficient—recrystalhzation of the mother liquors allows isolation of both enantiomers) , Ugi s lithiation provided the basis for a rapid growth in the use of enantiomerically pure, planar chiral ferrocenes which has continued since. Several reviews have covered applications of enantiomerically pure ferrocenes as chiral ligands, which until the 1990 s were all made using Ugi s method... 

Scheme 49 Oxazoline-NHC ligand bridge by a planar chiral ferrocene...

Naturally, it is possible to synthesise a similar ligand system without central chirality and in fact without the unnecessary methylene linker unit. A suitable synthesis starts with planar chiral ferrocenyl aldehyde acetal (see Figure 5.30). Hydrolysis and oxidation of the acetal yields the corresponding carboxylic acid that is transformed into the azide and subsequently turned into the respective primary amine functionalised planar chiral ferrocene. A rather complex reaction sequence involving 5-triazine, bromoacetal-dehyde diethylacetal and boron trifluoride etherate eventually yields the desired doubly ferrocenyl substituted imidazolium salt that can be deprotonated with the usual potassium tert-butylate to the free carbene. The ligand was used to form a variety of palladium(II) carbene complexes with pyridine or a phosphane as coligand. 

Many of the ferrocene ligand families described above are derived from a resolved chiral precursor (i.e. 289). Efforts to (76) prepare planar chiral ferrocenes also employ other strategies that rely on a directed metalation (see Orthometalation). Sulfoxide (338), acetal (339), and oxazolines of type (321)... 

Probably the most important class of planar-chiral ferrocenes accessible by the techniques delineated above is that of chelating ligands for transition-metal-catalyzed asymmetric reactions [1]. Progress in this area is characterized, among others, by ligands of type 16 [14], 17 [15], and 18 [16]. 

Finally, a completely new use of planar-chiral ferrocenes has been recently disclosed by Fu and co-workers [24]. Compounds of type 25 and 26 were prepared as racemic mixtures and obtained as pure enantiomers via semipreparative HPLC. Derivatives 25, analogues of 4-(dimethylamino)pyridine, were used as nucleophilic catalysts in the kinetic resolution of chiral secondary alcohols [24a,b]. The ami-noalcohol system 26, on the other hand, is an effective chiral ligand for the asymmetric addition of dialkylzinc reagents to aldehydes (up to 90% ee) [24c]. 

The development of novel chiral metal complexes and chiral ligands is crucial for both progress and development of asymmetric catalytic synthesis [1-3]. Within this area, the appearance of planar-chiral ferrocenes as ligands in asymmetric catalysis has been an important advancement [4-7]. While most of these complexes bear side chains or atom groups with stereogenic centres, it is often the 1,2-disubstitution pattern of the n-complexed ring that creates an inherent planar chirality [8] and exercises efficient stereochemical control. 

As a further extension, the You group reported a highly efficient synthesis of planar chiral ferrocenes via Pd-catalyzed annulation reactions of diary-lethynes (Scheme 5.11). The commercially available Af-Boc-L-Val-OH proved to be an efficient ligand with air as the sole oxidant. Ferrocenes with planar chirality could be synthesized with excellent enantioselectivity and moderate yields. A more sterically demanding P,N-ligand was easily prepared and showed enhanced enantioselective control in Pd-catalyzed allylic substitution reactions. 

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. ... 

Wang L, Kwok WH, Chan ASC, Tu T, Hou X, Dai L (2003) Asymmetric hydroesterification of styrene using catalysts with planar-chiral ferrocene oxazoline ligands. Tetrahedron Asym 14 2291-2295... 

Phosphorus is a key element in catalysis, and the last two Nobel prizes in molecular chemistry were awarded to Noyori, Sharpless and Knowles (2001) for their work on enantioselective catalysis and to Grubbs, Schrock and Chauvin (2005) for their work on the chemistry of transition metal carbene complexes and their applications in metathesis. In both cases the development of highly efficient, specifically tailored phosphorus based ligands are of paramount importance The book opens with an account of the recent studies on a new family of air-stable chiral primary phosphines based on the binaphthyl backbone and their applications in asymmetric hydrosilylations (Chap. 1). The concept of applying phosphorus ligands to enantioselective catalysis is also the main subject of Chaps. 5 and 10, dealing with P-based planar chiral ferrocenes and chiral phosphorus ligands for enantioselective enyne cycloisomerizations, respectively. 

Chiral ferrocenes have received niucli attenlion as ligands in metal-calalyzed reactions [39], bul tiieir use in copper cliemislry has been very limited [40, 41]. Hie ferrocene moiety offers die possibility of utilizing botli central and planar cliirality in die ligand. By analogy witli tlie copper arenetiiiolales described above, ferrocenyl copper complex 33 iSclieme 8.20) is extremely inleresling. 

Extending the same concept of a planar chiral nucleophilic or basic heterocyclic Fe-sandwich complex, aza-ferrocenes 65 were prepared. The latter have also been successfully applied as bidentate ligands in transition metal catalysis [85]. 

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