Aldehydes, enantioselective addition

Keywords aldehyde, enantioselective addition, diethylzinc, secondary alcohol... 

The first reported chiral catalysts allowing the enantioselective addition of diethylzinc to aryl aldehydes in up to 60% cc were the palladium and cobalt complexes of 1,7,7-trimethylbicy-clo[2.2.1. ]heptane-2,3-dione dioxime (A,B)3. A number of other, even more effective catalysts, based on the camphor structure (C K, Table 26) have been developed. 

Recently, the enantioselective addition of hydrocyanic acid to aldehydes, analogous to the synthesis of (/ )-cyanohydrins, yielding (.S)-cyanohydrins in very high optical purity, with (S )-oxynitrilase as catalyst, was reported20,21. 

A polymer-supported version of our optimal ligand was also developed [52]. Its preparation involves attachment of aziridine carbinols to polymer-bound triphenylchloromethane (Scheme 40). This polymer-bound ligand 53 was almost equally effective in the enantioselective addition of diethylzinc to aromatic and aliphatic aldehydes with ee s ranging from 77-97% for the latter type of substrate [52]. It is of practical interest that this polymer-supported ligand could be reused without losing much of its efficiency. 

Enantioselective addition of P-H bonds in dialkyl phosphites to aldehydes and imines has been studied in detail. These reactions typically use early metal or Ian-... 

The discussion of the activation of bonds containing a group 15 element is continued in chapter five. D.K. Wicht and D.S. Glueck discuss the addition of phosphines, R2P-H, phosphites, (R0)2P(=0)H, and phosphine oxides R2P(=0)H to unsaturated substrates. Although the addition of P-H bonds can be sometimes achieved directly, the transition metal-catalyzed reaction is usually faster and may proceed with a different stereochemistry. As in hydrosilylations, palladium and platinum complexes are frequently employed as catalyst precursors for P-H additions to unsaturated hydrocarbons, but (chiral) lanthanide complexes were used with great success for the (enantioselective) addition to heteropolar double bond systems, such as aldehydes and imines whereby pharmaceutically valuable a-hydroxy or a-amino phosphonates were obtained efficiently. 

In 1998, Anderson et al. developed a new series of S/N ligands derived from L-valine and analysed these in the enantioselective addition of ZnEt2 to aromatic aldehydes. The use of these ligands allowed enantioselectivities of up to 82% ee to be obtained (Scheme 3.10). The results showed that the ligands possessing symmetrical nitrogen substituents did not perform as well as those... 

In 2002, Braga et al. reported the enantioselective addition of ZnEt2 to various aldehydes performed in the presence of chiral imidazolidine disulfides derived from L-cysteine. In the presence of 5mol% of ligand, the secondary alcohols were isolated in enantioselectivities of up to 91% ee. Aromatic... 

On the other hand, novel diastereomeric p-amino thiol ligands possessing an isoquinuclidine skeleton have been readily prepared by Hongo et al. via imino-Diels-Alder reactions.As shown in Scheme 3.15, when applied to the enantioselective addition of ZnEt2 to various aldehydes, one of these ligands afforded the products with high enantioselectivities of up to 94% ee. 

In addition, other chiral sulfide ligands containing oxazolidines have been tested for the enantioselective addition of ZnEt2 to aldehydes, providing moderate enantioselectivities, as shown in Scheme 3.25. ... 

Numerous chiral non-S-coordinating bis(sulfonamides) have been successfully involved in the enantioselective addition of various organozinc reagents to aldehydes since the first use of tr<2 5-l(i ),2(i )-bis(trifluoromethanesulfo-namido)cyclohexane reported in 1989 by Ohno et These authors demonstrated the usefulness of this ligand in the Ti-catalysed enantioselective addition of ZnR2 to a variety of aldehydes, allowing enantioselectivities of up to 99% ee to be obtained (Scheme 3.37). 

On the other hand, excellent enantioselectivities of up to 98% ee have been obtained by Gau et al. for the Ti-catalysed enantioselective addition of ZnEt2 to aldehydes in the presence of Y-sulfonylated amino alcohols as ligands (Scheme 3.49). ... 

The preparation and the use of several C2-symmetric disulfonamides derived from 1,2-amino alcohols in the Ti-catalysed enantioselective addition of di-alkylzinc reagents to aldehydes was described by Yus et al., in 2002. The best... 

In order to synthesise the pyrrolidine alkaloid, (-l-)-197B, bis-(i ,i )-tri-fluoromethanesulfonamide ligand was employed in the enantioselective addition of Zn( -Bu)2 to an allene-aldehyde, alfording the corresponding (i )-alcohol in 70% yield and 94% ee (Scheme 3.52). ... 

On the other hand, several S/O ligands have been successfully applied to the enantioselective addition of ZnEt2 to aldehydes. As an example, Aral et al. have developed isoborneol-derived p-hydroxy-sulfide ligands and employed them in the enantioselective addition of ZnEt2 to benzaldehyde, providing enantio-selectivities of up to 88% ee (Scheme 3.54). These authors showed that the enantioselectivity of the reaction did not depend on the substituent of the sulfur atom. 

In 2005, a novel C2-symmetric bis(sulfonamides) ligand was easily prepared in three steps by Wang et al. and further applied to the enantioselective addition of alkynylzine reagents to aldehydes performed in the presence of Ti(Oi-Pr)4. When a catalyst loading of 4 mol% was used, a high enantioselectivity of up to 97% ee was achieved, as shown in Scheme 3.65. When the amount of the... 

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

On the other hand, S/O ligands have been developed to a lesser extent, but their efficient use as chiral ligands was proven in the enantioselective addition of diethylzinc to aldehydes and also in the copper-catalysed asymmetric conjugate addition. 

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