Catalyzed Asymmetric Aryl Transfer Reactions

In early 1990 we began to work on catalyzed carboligations using organozinc reagents [1]. The reactions commonly involved diethylzinc 2, which was added enantioselectively to aldehydes 1 affording secondary alcohols 3. Initially, bipyridine 4 [2-6], pyridine 5 [3], and sulfoximines 6 [7] were applied as catalysts, which in some cases led to enantioselectivities greater than 95% ee [8, 9]. 

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- 

The development of ferrocene 9 was part of our studies on planar-chiral compounds, which also involved the synthesis of other scaffolds such as chromium-tricarbonyl arenes [15], sulfoximidoyl ferrocenes [16], and [2.2]paracyclophanes [17]. In aryl transfer reactions, however, ferrocene 9 proved to be the best catalyst in this series, and it is still used extensively today. 

With other electrophiles, ferrocenes 12 and 13 could be obtained, bearing a selenium group [19] or a silanol moiety [20], respectively, in the ortho position. Those compounds proved to be catalytically active as well, and in particular 13 was of interest, since - to the best of our knowledge - it was the first silanol ever used as a chiral ligand in asymmetric catalysis. Details of this study will be discussed below. 

The same synthetic strategy as in the synthesis of planar-chiral ferrocenes was applied to the preparation of rheniumtricarbonyl 14, which has also been studied as a catalyst in aryl transfer reactions [21], Subsequently, this chemistry has been extended, and various catalytic applications of cyrhetrenes 15, 16 (AAPhos), and related derivatives have recently been demonstrated [22]. 

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For a general review of catalyzed asymmetric aryl transfer reactions, see C. Bolm, J. P. Hildebrand, K. Muniz, N. Hermanns, Angew. Chem. 2001, 113, 3382 Angew. Chem. Int. Ed. 2001, 40, 3284. 

Scheme 7.45 Use of arylboronic acids in the Fe-catalyzed asymmetric aryl transfer reaction, as reported by Bolm and Rudolph [74].

Although the precise reason for the MPEG-effect [50] is still unknown, we assume that catalytically active achiral metal species are inactivated by trapping with the polyether and that the catalyzed asymmetric reaction path thereby becomes more dominant. This phenomenon had already been observed in aryl transfer reactions catalyzed by MPEG-bound ferrocene 39 [44], and it can be used to perform catalyses with lower catalyst loadings [50]. 

Asymmetric Transfer Hydrogenation of Ketones. The first reports on asymmetric transfer hydrogenation (ATH) reactions catalyzed by chiral metallic compounds were published at the end of the seventies. Prochiral ketones were reduced using alcohols as the hydrogen source, and Ru (274,275) or Ir (276) complexes were used as catalysts. Since then, many chiral catalytic systems for homogeneous ATH of ketones, imines, and olefins have been developed (37,38,256,257,277-289). The catalytic systems are usually based on ruthenium, rhodium, or iridium, and the ATH of aryl ketones is by far the most studied. Because of the reversibility of this reaction, at high conversions, a gradual erosion of the ee of the product has been frequently reported. An azeotropic 5 2 mixture of formic acid/triethylamine can be used to overcome this limitation. 

Almost at the same time, Liu and Che published a cascade intermolecular hydroamination/asymmetric reduction sequence, which included achiral Au complex-catalyzed hydroamination of aryl amines and chiral phosphoric acid-promoted Hantzsch ester reduction to afford secondary aryl amines [70], More recently, the same group reported a tandem one-pot assembly of functionalized tetrahydroquino-lines from amino aldehyde and alkynes by combining Au and chiral phosphoric acid catalysis [71], The reaction was initiated by Au-promotedquinololine 210 generation, followed by an enantioselective HEH-incorporated transfer hydrogenation process (Scheme 9.67). 

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