Chiral spiro ligands

Compared with well-established electrophilic it-allylpalladium chemisty, the catalytic asymmetric reaction via umpolung of jt-allylpalladium has received very limited exploration [93]. Zhou and co-workers investigated the Pd-catalyzed asymmetric umpolung allylation reactions of aldehydes [22a, 94], activated ketones [95], and imines [96] by using chiral spiro ligands (5)-18e, (S)-17c, and (5)-17a, respectively. One representative example is that of the Pd/(5)-18e-catalyzed umpolung allylation of aldehydes with allylic alcohols and their derivatives, which provided synthetically useful homoallylic alcohols from readily available allylic alcohols, with high yields and excellent enantioselectivities (Scheme 33). 

Professor Zhou s group from Nankai University reported that chiral spiro ligands developed in their laboratory cooperated with monovalent copper can catalyze intramolecular asymmetric O-H bond insertion, which could be used to construct various ring systems, including five-, six- and seven-membered ring [10]. Catalyzed by copper(I), the a-diazo carbonyl compounds containing primary... 

Currently, this area is not as well developed as the use of cinchona alkaloid derivatives or spiro-ammonium salts as asymmetric phase-transfer catalysts, and the key requirements for an effective catalyst are only just becoming apparent. As a result, the enantioselectivities observed using these catalysts rarely compete with those obtainable by ammonium ion-derived phase-transfer catalysts. Nevertheless, the ease with which large numbers of analogues - of Taddol, Nobin, and salen in particular- can be prepared, and the almost infinite variety for the preparation of new, chiral metal(ligand) complexes, bodes well for the future development of more enantioselective versions of these catalysts. 

Cobalt(II) complexes prepared in situ from (AcO Co and two novel chiral spiro nitrogen-containing ligands, 7,7/-bis(2-pyridinecarboxamido)-l,l/-spirobiindane (SIPAD) and 7,7/-bis(2-quinolinecarboxamido)-l,l/-spirobiindane (SIQAD), are efficient cata- lysts for the asymmetric Michael addition of malonates to chalcone derivatives. The alkylation products were obtained in high yields with moderate enantioselectives.169... 

Isoxazoline rings include two heteroatoms which could serve as Lewis bases. Chiral spiro bis(isoxazoline) ligands, named SPRIXs, bearing a chiral spiro skeleton and two isoxazoline rings, have been reported <19990L1795>. 

Figure 2 Chiral spiro phosphorous ligands with spiro[4.4]nonane, spiro[2.2]pentane and dispiro[2.0.2.1]heptane scaffolds...

Figure 3 Chiral dinitrogen ligands with fused hetero spiro backbone...

The high rigidity is the key feature of the chiral spirobiindane ligands, which exhibited special advantages in many asymmetric reactions. One example is the Cu complex of chiral spiro bisoxazoline ligand (S, S,S)-23a (R=Ph). Zhu et al. [33] analyzed the X-ray structures of Cu(I)-(5, 5,5)-23a with various anions (PF, C10 , and BArp). All the complexes have an unexpected binuclear Cu structure, as shown... 

A novel class of complexes, Ir-(5 )-26a, with chiral spiro aminophosphine ligands was found to be effective catalyst for the asymmetric hydrogenation of a-substituted acrylic acids (Scheme 11) [62]. Under mild reaction conditions and at ambient pressure, various a-aryl and alkyl propionic acids were produced with extremely high efficiency (TONS up to 10 000 TOFs up to 6000h ) and excellent enantioselectivity (up to 99% ee). This reaction provides a practically useful method for the preparation of a-aryl propionic acids, a popular class of non-steroid anti-inflammtory reagents. 

Hoffman and Carreira [31] reported a Rh-catalyzed asymmetric intramolecular hydroacylation of pent-4-enal substrates, providing P-substituted cyclopentanones in good yield and excellent selectivity by using chiral spiro phosphoramidite-alkene ligand (R)-29 (Scheme 29). 

A spiroketal bisphosphine (R R,R)-38a derived chiral Au complex was found to be an efficient catalyst for asymmetric cyclopropanation of diazooxindoles with a broad range of aUcenes, providing a highly diastereo- and enantioselective approach for spiro cyclopropyloxindoles (Scheme 41) [47]. These results further demonstrate the special advantage of rigid spiro ligands in Au-catalyzed reactions. 

By using Cu complexes of chiral spiro bis(oxazoline) ligand S, S,S)-23a as catalysts, the enantioselective catalytic insertion of a-diazoesters into N—H bond of aromatic amines was realized in high yields and high enantioselectivities (Scheme 43) [25b, 108]. The chiral spiro Cu catalysts have unique binuclear structures, as showing in Figure 6, which may address the excellent performance of the Cu-(S, S,S)-23a catalyst for this challenging reaction. With the Cu-catalyzed asymmetric N—H... 

It was found that the iron catalysts prepared in situ from FeCl -dH O and chiral Spiro bisoxazoline ligands 23 exhibited excellent enantioselectivity as well as reactivity for the insertion of O—H bonds of various saturated alcohols and allylic alcohols (Scheme 46) [111]. The catalyst Fe-(S, S,S)-23c showed higher yields and higher enantioselectivities than any other metal catalysts. 

The asymmetric insertion of a-diazoesters into the O—H bond of water provides an extremely simple approach for the synthesis of chiral a-hydroxyesters in an efficient and atom-economical way. The challenges of asymmetric O—H insertion of water are mainly attributed to two considerations first, the active metal carbene intermediates are generally sensitive to water and secondly, the small molecular structure of water makes chiral discrimination quite difficult. Zhou and co-workers discovered a highly enantioselective O—H insertion of water catalyzed by chiral spiro Cu [112] and Fe catalysts [111]. Under mild conditions, both Cu andFe complexes of ligand (S, 5,5)-23a... 

Transition metal catalyzed carbene insertion into the Si—H bond provides a direct and efficient method for the synthesis of organosilicon compounds. When chiral spiro diimine ligand (/ )-24a was applied in Cu-catalyzed asymmetric insertion of a-diazo-a-arylacetates with silanes, the Si—H insertion products were obtained in high yields (85-97%) and excellent enantioselectivities (90-99% ee) (Scheme 51) [26a],... 

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