Ferrocenyloxazoline

Anderson CE, Donde Y, Douglas CJ, Overman LE (2005) Catalytic asymmetric synthesis of chiral allylic amines. Evaluation of ferrocenyloxazoline palladacycle catalysts and imidate motifs. J Org Chem 70 648-657... 

In 2000, other S/N-ferrocenyloxazolines were prepared by Ai t-Haddou et al. starting from ehiral 2-amino-3-phenyl-l,3-propanediol. The corresponding P/N-analogues were also prepared in order to compare their efficiency in the test reaction. As shown in Scheme 1.68, both ligands gave good results in terms of both activity and enantioselectivity with a better result for the S/N ligand. 

In 2003, Bonini et al. reported a new synthesis of ferrocenyloxazolines based on an iodide-mediated ring expansion of A-ferrocenoyl-aziridine-2-carboxylic esters. The thus-formed ligands were successfully employed as palladium chelates for the test reaction, since they allowed the product to be formed in quantitative yields and good to high enantioselectivities (Scheme 1.69). According to the results, it seemed that the additional chiral centre present in the oxazoline backbone of these ligands did not play a major role for the asymmetric induction and the activity of the corresponding catalysts. 

Scheme 1.67 Test reaction with sulfur-containing ferrocenyloxazoline ligands.

Scheme 1.68 Test reaction with S/N- and P/N-ferrocenyloxazoline ligands.

Scheme 1.69 Test reaction with S/N-ferrocenyloxazoline ligands bearing two stereogenic centres.

In addition, Bryce et al. have studied the binding of palladium to other S/N-ferrocenyloxazoline ligands by cyclic voltammetry and proved that it was reversible.These redox-active liganding systems were successfully used in the test reaction, providing the product in both high yield and enantioselectivity of up to 93% ee, as shown in Scheme 1.70. 

Lithiation of the conformationally constrained ferrocenyloxazoline 308 (Scheme 142) provided useful information about the mechanism by which lithiation of 305 achieves diastereoselectivity . The product 310 must have arisen from an organolithium 309 in which the oxazoline nitrogen coordinates to the hthium (Scheme 142). It is likely that... 

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 ". ... 

In removing the oxazoline auxiliary from the products, Richards and coworkers have demonstrated the use of the diastereoselective ferrocenyloxazoline lithiation in the synthesis of conformationally constrained amino acid derivatives (Scheme 146) °. Amination of 305 was achieved by nitration, reducing to the amino group after removal of the oxazoline under standard conditions. Using the trick of silylating the more reactive diastereotopic site, it was possible to make either enantiomer of 321 from the same oxazoline starting material. 

Subsequent smdies revealed the scope and generality of this reaction that has been employed extensively for the synthesis of chiral ferrocenyloxazoline ligands." " Selected examples are listed in Table 8.26 (Scheme 8.142). " Sammakia and Latham optimized the reaction conditions... 

Another significant development in oxazoline chemistry is the application of oxazoline-containing ligands for asymmetric catalysis, such as palladium-catalyzed allylic substimtions, Heck reactions, hydrogenations, dialkylzinc additions to aldehydes, and Michael reactions. The discovery of diastereoselective metalation of chiral ferrocenyloxazolines has further expanded the availability of chiral ligands for metal-catalytic reactions. 

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." " ... 

Side-chain functional group transformations of phosphinoferrocenes have again found application in the synthesis of new phosphines. A variety of side-chain modification routes have been used in routes to a series of phosphino-functionalised ferrocenyloxazolines. Well-established nucleophilic displacements using primary or secondary... 

Sutcliffe OB, Bryce MR (2003) Planar chiral 2-ferrocenyloxazolines and 1,1 -bis(oxazolinyl)ferrocenes-syntheses and applications in asymmetric catalysis. Tetrahedron Asym 14 2297-2325... 

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