TADDOL-derived chiral ligands

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

In total, 29 pbospborus-containing chiral ligands of various structures were screened under tlie optimized ji-selective condhions, but most of tlieni gave little or no chiral induction. Hie four ligands 38a-d, all derived from i-)-TADDOL, depicted in Fig. 8.4 gave tts in excess of 3096 in the reaction between etliyl magnesium bromide and cinnamyl cliloride. 

The use of TADDOL-based ligands offers an important alternative for copper-catalyzed asymmetric 1,4-additions. TADDOLs (a, a, a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol compounds), introduced by Seebach, are among the most successful currently known ligands in asymmetric catalysis. Seebach also developed the first copper-catalyzed 1,4-addition of a Grignard reagent using a TADDOL derivative as a chiral ligand (see Scheme 7.2) [17]. We have reported TADDOL-based... 

A highly enantioselective synthesis of a-dehydroamino acids (186) with a stereogenic centre at the y -position has been developed, which employs a copper-catalysed asymmetric conjugate addition of diethylzinc to a,j3-unsaturated imines (185) with the TADDOL-derived phosphoramidite (187) as a chiral ligand.234... 

Nonracemic Ti-BINOLate (BINOL = l,l -bi-2-naplilli()l) and Ti-TADDOLate (TADDOL = a,a,a, a -tetraaryl-2,2-dimethyl-l,3-dioxolan-4,5-dimethanol) complexes are also effechve chiral catalysts for the asymmetric alkylation of aldehydes [9-11]. Seebach developed polystyrene beads with dendritically embedded BINOL [9] or TADDOL derivatives 11 [10, 11]. As the chiral ligand is located in the core of the dendritic polymer, less steric congeshon around the catalyhc center was achieved after the treatment with Ti(OiPr)4. This polymer-supported TiTADDOLate 14 was then used for the ZnEt2 addition to benzaldehyde. Chiral 1-phenylpropanol was obtained in quantitahve yield with 96% ee (Scheme 3.3), while the polymeric catalyst could be recycled many times. 

An ideal chiral ligand should not only be easily accessible but it should also be possible to modify its structure systematically. In this way the catalyst structure can be optimized for a specific application or substrate structure. Therefore, it is not surprising to see a clear trend toward modular ligands that can be readily assembled from a large selection of simple precursors. Good examples of such modular ligands are salens, phosphinooxazolines or TADDOLS, which are derived from inexpensive chiral diamines, amino alcohols and tartrate, respectively. 

Seebach et al. have comprehensively examined the use of a chiral diol (TAD-DOL) derived from tartaric acid as a chiral ligand [22]. The titanium-TADDOL system also catalyzes the asymmetric addition of diethylzinc to various aldehydes (Scheme 8) [23,24]. This system is applicable to the alkylation of various... 

Other enantioselective catalysts for the D-A reactions have been developed. The chiral ligands used include the TADDOLs (a, a, a, a-tetraaryl-l,3-dioxolane-4,5-dimethanols) ° and BINOL derivatives. These are discussed in Section 6.4 of Part B. 

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