Planar Chiral Catalysts

The enantioselective discrimination of one of the hydroxyl groups of meso-diols can give chiral monoprotected diols, which serve as versatile intermediates for asymmetric organic synthesis. In addition to the enzymatic methods, a number of chemical approaches have been reported using chiral 1,2-diamine catalysts, chiral phospholane-based catalysts, planar chiral DMAP derivatives, and oligopeptide-based catalysts [2,28], Surprisingly, however, relatively a few publications are devoted to this reaction with cinchona-based organocatalysts. 

Although boron is a metalloid, one can nonetheless include boron-derived compounds in a book on organocatalysis as not being transition metal containing catalysts Planar chiral boronic acids have been employed as amide couphng catalysts, actually as bifunctional Lewis acid/base activators. Whiting s [51] group reported the preparation [52] of two amino-boronic ferrocenes (see Scheme 8.17). Their use... 

Planar Chiral Ferrocenes as Lewis- or Br0nsted-Base Catalysts.163... 

Palladacycles are defined as compounds with a Pd-C CT-bond with the Pd being stabilized by one or two neutral donor atoms, typically forming 5- or 6-membered rings [51]. Ferrocenyl palladacycles constitute a particularly attractive catalyst class partly due to the element of planar chirality. The first diastereoselective cyclopallada-tion of a chiral ferrocene derivative was reported in 1979 by Sokolov [52, 53]. 

In 1997 the first asymmetric aza-Claisen rearrangement was reported by Overman et al. [55], which made use of diamines as bidentate ligands for Pd(II), allowing for moderate enantioselectivities. In the same year, Hollis and Overman described the application of the planar chiral ferrocenyl palladacycle 38 as a catalyst for the enantioselective aza-Claisen rearrangement of benzimidates 39 (Fig. 19) [56]. A related ferrocenyl imine palladacycle provided slightly inferior results, while a benzylamine palladacycle lacking the element of planar chirality was not able to provide any enantioselectivity [57]. 

The [Fe-Cp]-fragment does not only play the role of an additional steric element introducing planar chirality into the otherwise flat pyridine system. Substitution at the pyridine 2-position usually cuts the nucleophilicity of the nitrogen atom thus limiting the possibilities to achieve efficient chirality transfer using nucleophilic pyridine catalysts [84]. Ferrocene, however, functions as a strong electron donor (see Sect. 1) and thus restores the nucleophilicity impaired by substitution. 

Enantioenriched alcohols and amines are valuable building blocks for the synthesis of bioactive compounds. While some of them are available from nature s chiral pool , the large majority is accessible only by asymmetric synthesis or resolution of a racemic mixture. Similarly to DMAP, 64b is readily acylated by acetic anhydride to form a positively charged planar chiral acylpyridinium species [64b-Ac] (Fig. 43). The latter preferentially reacts with one enantiomer of a racemic alcohol by acyl-transfer thereby regenerating the free catalyst. For this type of reaction, the CsPhs-derivatives 64b/d have been found superior. 

Other reactions not described here are formal [3 -i- 2] cycloadditions of a,p-unsaturated acyl-fluorides with allylsilanes [116], or the desymmetrization of meso epoxides [117]. For many of the reactions shown above, the planar chiral Fe-sandwich complexes are the first catalysts allowing for broad substrate scope in combination with high enantioselectivities and yields. Clearly, these milestones in asymmetric Lewis-base catalysis are stimulating the still ongoing design of improved catalysts. 

Cohen F, Overman LE (1998) Planar-chiral cyclopalladated ferrocenyl amines and imines as enantioselective catalysts for allylic imidate rearrangements. Tetrahedron Asymmetry 9 3213-3222... 

Tao B, Ruble JC, Hole DA, Fu GC (1999) Nonenzymatic kinetic resolution of propargylic alcohols by a planar-chiral DMAP Derivative crystallographic characterization of the acylated catalyst. J Am Chem Soc 121 5091-5092... 

Tao B, Lo MMC, Fu GC (2001) Planar-chiral pyridine N-oxides, a new family of asymmetric catalysts exploiting an rj -CsArs ligand to achieve high enantioselectivity. J Am Chem Soc 123 353-354... 

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. 

Until now, only a few effective ligands of this type have been identified (Fig. 25.4). Kagan and co-workers [5] prepared one of the few chiral diphosphines with only planar chirality and obtained 95% ee for the hydrogenation of DM IT with LI (Table 25.1, entry 1.1.), but enantioselectivities for several enamide derivatives were below 82% ee (the best results were with the cyclohexyl analogue of LI). For the reactions with DM IT or MAC, the cationic Rh-kephos complex showed comparable or better performance than corresponding duphos catalysts. 

A number of laboratories have targeted chiral DMAP analogs as acylation catalysts with perhaps the best success realized by Fu s planar chiral ferrocenyl... 

The first class of amine-based nucleophilic catalysts to give acceptable levels of selectivity in the KR of aryl alkyl. yec-alcohols was a series of planar chiral pyrrole derivatives 13 and 14, initially disclosed by Fu in 1996 [25, 26]. Fu and co-workers had set out to develop a class of robust and tuneable catalysts that could be used for the acylative KR of various classes of. yec-alcohols. Planar-chiral azaferrocenes 13 and 14 seemed to meet their criteria. These catalysts feature of a reasonably nucleophilic nitrogen and constitute 18-electron metal complexes which are highly stable [54-58]. Moreover, by modifying the substitution pattern on the heteroaromatic ring, the steric demand and hence potentially the selectivity of these catalysts could be modulated. 

Differentiation top from bottom and left from right Fig. 3 Fu s design of a planar-chiral catalyst derived from pyrrole [69]... 

Hence, the group developed a series of planar chiral ferrocenyl 4-DMAP and 4-(pyrrolidino)pyridine (4-PPY) derivatives (15-18) that have proved to be highly versatile and efficient catalysts for many acyl transfer processes (Fig. 5) [25, 26, 66-82, 93, 99, 103, 105]. 

Scheme 5 Fu s first generation planar-chiral catalyst for the KR of a iec-alcohol [25]...

Fig. 4 Fu s concept for a planar-chiral 4-DMAP catalyst based on his pyrrole planar-chiral ...

Fu s planar chiral ferrocenyl 4-DMAP derivative 16 is also the first organocatalyst that has been reported to efficiently perform the KR of certain propargylic ec-alcohols [83]. These KRs were achieved using 1 mol% of catalyst 16 and Acp as the acylating agent in tert-smyl alcohol at 0 °C in the absence of a stoichiometric auxiliary base... 

Eu s planar chiral ferrocenyl 4-DMAP catalyst 16 was also shown to be effective for the ASD of mei o-diols as illustrated for the case of unusual meso-diol 22 (Scheme 9) [81]. 

In addition to the planar chiral ferrocenyl catalysts 15-18, 24 developed by Fu, a number of other chiral derivatives of 4-DMAP and 4-PPY [4, 47, 48] have been explored by other groups as organocatalysts for KR of ec-alcohols. Contributions have been made by the groups of Vedejs [104, 105, 110, 111], Fuji and Kawabata... 

Given that the Birman catalysts are readily prepared in just two steps from commercially available enantiomerically pure phenylalaninol, these catalysts constitute attractive alternatives to Fn s planar chiral ferrocenyl catalysts 15-18. 

In 2000, we demonstrated that the planar-chiral phosphaferrocene PF-PPhj is a useful ligand for rhodium-catalyzed asymmetric isomerizations of several allylic alcohols, providing the first catalyst system that furnishes the target aldehyde in >60% ee (Eq. 6) [7]. It appears that, in order to obtain high enantiomeric excess (>0% ee), the olefin should bear a relatively bulky substituent (for example, Pr Eq. 6). 

Bidentate ferrocene ligands containing a chiral oxazoline substituent possess both planar chiral and center chiral elements and have attracted much interest as asymmetric catalysts.However, until recently, preparation of such compounds had been limited to resolution. In 1995, four groups simultaneously communicated their results on the asymmetric synthesis of these structures using an oxazoline-directed diastereoselective lithiation (Scheme 8.141). " When a chiral oxazolinylferrocene 439 was metalated with butyllithium and the resulting aryllithium species trapped with an electrophile, diastereomer 442 was favored over 443. The structure of the major diastereomer 442 was confirmed, either by conversion to a compound of known stereochemistry or by X-ray crystallography of the product itself or of the corresponding palladium complex. ... 

In the late 1990s the focus of our work changed in two respects. First, we started to use planar-chiral ferrocene 9 as a catalyst [10, 11], and second, instead of applying the well-investigated dialfeylzinc reagents [12], we began to explore reac-... 

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