Ferrocene oxazoline

Fig. 27 Synthesis of pentaphenyl ferrocene oxazoline palladacycle precatalyst 53-Cl...

In 2005, Riant et al. reported the synthesis of a new air-stable S/N-chelating zinc catalyst, depicted in Scheme 10.50, which was fully characterised by all spectroscopic methods. This complex, prepared from the corresponding ferrocene oxazoline, was applied to the enantioselective hydrosilylation of ketones in the presence of polymethylhydrosiloxane, PMHS, providing modest enan-tioselectivities (<55% ee). ... 

The ferrocene-oxazoline catalyst 19 (Fig. 29.7) has recently been used to hydrogenate substituted quinolines [18]. The ligand synthesis is again similar to that of the original PHOX ligand, with introduction of phosphorus via orthometallation. 

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... 

A related planar chiral Co-based oxazoline palladacycle COP-X (46) was later found to be of higher synthetic utility as it permitted the use of benzimidates, [62] as well as allylic trifluoro- [63] and trichloroacetimidates [64, 65]. 46 was found to be superior to its ferrocene analogue 41 [61] in a number of aspects such as ease of... 

Moyano A, Rosol M, Moreno RM, Lopez C, Maestro MA (2005) Oxazoline-mediated interannular cyclopalladation of ferrocene chiral palladium(II) catalysts for the enantioselective Azti-Claisen rearrangement. Angew Chem Int Ed 44 1865-1869... 

In an approach to planar chiral ferrocenes, Siegel and Schmalz (85) report that bis(oxazoline)-copper complexes induce efficient aromatic C-H insertion from a... 

Attempts to make C2-symmetric ferrocenes by double lithiation of a bis-acetal met with only limited success . A second lithiation of the ferrocenylacetal 298 leads to functionalization of the lower ring of the ferrocene, in contrast with the second adjacent lithiation of the oxazolines described below. This can be used to advantage if, for example, the first-formed aldehyde 301 is protected in situ by addition of the lithiopiperazine 53 °, directing f-BuLi to the lower ring (Scheme 139) °. The same strategy can be used to introduce further functionalization to products related to 302. For example, silane 303, produced in enantiomerically pure form by the method of Scheme 138, may be converted to the ferrocenophane 304 by lithiopiperazine protection, lithiation and functionalization (Scheme 140) . 

Although oxazolines can be used as auxiliaries and later removed they have also been retained in target molecules which have then been used as ligands for a variety of asymmetric transformations. Ferrocenes carrying oxazoline and phosphine coordination sites ° ° " , oxazoline and amine coordination sites, and ferrocene bis-oxazoli-nes have been synthesized by the method of Scheme 141. 

A ferrocenyloxazoline with only one adjacent position available for deprotonation will lithiate at that position irrespective of stereochemistry. This means that the same oxazoline can be used to form ferrocenes with either sense of planar chirality. The synthesis of the diastereoisomeric ligands 311 and 313 illustrates the strategy (Scheme 143), which is now commonly used with other substrates to control planar chirality by lithiation (see below). Ferrocene 311 is available by lithiation of 305 directly, but diastereoselective silylation followed by a second lithiation (best carried out in situ in a single pot) gives the diastereoisomeric phosphine 313 after deprotection by protodesilylation ". ... 

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. ... 

Dilithiation of a C2-symmetric bis(oxazoline)-substituted ferrocenes as well as biaryls provides a versatile method for preparation of C2-symmetric tetradentate ligands. This reaction was originally described in 1995 by Park, Ahn, and co-workers. The same group and others have further expanded this reaction to... 

The synthesis of ferrocene 9 relied on chemistry introduced by Sammakia, Uemura, and Richards [18]. They had shown that 2-ferrocenyl oxazoline 10 derived from t-leucine could be selectively deprotonated and trapped with electrophiles to afford ortho-functionalized planar-chiral products 11 with excellent diastereoselectivities (Scheme 2.1.2.3). Following this strategy, 9 became accessible in a highly straightforward manner by trapping the lithiated intermediate derived from 10 with benzophenone [10, 11],... 

Ferrocenes of type 11 (as well as cyrhetrenes such as 14) are characterized as having two elements of chirality a stereogenic center at the oxazoline ring and a plane of chirality due to the two ortho substituents on the ferrocene core. 

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

Chiral bis(oxazolines) 51 with an oxalylic acid backbone were used for the Ru-catalyzed enantioselective epoxidation of tran5-stilbene yielding franx-l,2-diphenyloxirane in up to 69% ee [24]. The asymmetric addition of diethylzinc to several aldehydes has been examined with ferrocene-based oxazoline ligand 52 [25], resulting in optical yields from 78-93% ec. The imide 53 derived from Kemp s triacid containing a chiral oxazoline moiety was used for the asymmetric protonation of prochiral enolates [26]. Starting from racemic cyclopentanone- and cyclohexanone derivatives, the enantioenriched isomers were obtained in 77-98 % ee. 

Ferrocenoyl chloride (318), ethyl ferrocenecarboxylate (319), and cyanoferrocene (320) are all used as starting materials for the synthesis of 2-ferrocenyloxazolines (321) (Scheme 87). Chirality may be incorporated into the oxazoline ring, and these important chiral compounds have been used to prepare a great number of ferrocene derivatives that are used as catalysts in asymmetric synthesis." " ... 

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)... 

Lithioferrocene (322) or dilithioferrocene (323) can also be prepared, and then utilized in situ, from the corresponding halo- or dihaloferrocenes by halogen-metal exchange with alkyl lithiums. Alternatively, monohthiation of l,l -dibromoferrocene gives rise to anion (351), which may be reacted with an electrophile in order to afford additional ferrocene derivatives. In this way, monophosphine oxazoline ferrocene (340) is prepared from bromo oxazoline ferrocene (352), a compound that also is used to prepare chiral-at-phosphorus ferrocenes (353). Other chiral-at-phosphoras ferrocenes (354) are made from (323) and a phosphite borane as the electrophile (equation 80). The phosphorus atoms may also be contained in a ring that possesses chirality the sequences used to prepare this family... 

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