Sulfonamide Ligands

The following C2-symmetric bis-sulfonamide is a more efficient controller of stereoselectivity in aldol additions. The incorporation of this ligand into the bromodiazaborolane, subsequent generation of the boron enolate derived from 3-pentanone, and addition to achiral aldehydes preferentially leads to the formation of ijn-adducts (synjanti 94 6 to >98 2) with 95-98% ee. Chemical yields of 85-95% are achieved51. 

The ZwKKER reaction involving Co salts is frequently used for the detection of barbituric acid derivatives [31-35], but some purine, pyridine and piperidine derivatives and heterocyclic sulfonamides also yield colored derivatives. The Zwkker reaction is particularly sensitive when it is possible to form a tetrahedral complex [Co(Barb)2 Xj] (X = donor ligand, e.g. amine) [4]. 

It was found, furthermore, that the substituent on the sulfonamide group of the chiral hgand strongly influenced the enantiofacial selectivity. Hence, ligand 81 bearing a tosyl substituent delivered the endo-(2il)-cycloadduct, whereas a trifluoromethanesulfonamide group afforded its enantiomer. The authors proposed that the latter substituent should increase the Lewis acid-... 

Another important function of albumin is its ability to bind various ligands. These include free fatty acids (FFA), calcium, certain steroid hormones, bilirubin, and some of the plasma tryptophan. In addition, albumin appears to play an important role in transport of copper in the human body (see below). A vatiety of drugs, including sulfonamides, penicilhn G, dicumarol, and aspirin, are bound to albumin this finding has important pharmacologic implications. 

Palladium-catalysed asymmetrie allylations of various carbonyl compounds have been studied by Hiroi et al. using various types of chiral sulfonamides derived from a-amino acids. In particular, the chiral bidentate phosphinyl sulfonamide derived from (5)-proline and depicted in Scheme 1.63 was employed in the presence of palladium to eatalyse the allylation of methyl aminoacetate diphenyl ketimine with allyl aeetate, leading to the eorresponding (7 )-product with a moderate enantioseleetivity of 62% ee. This ligand was also applied to the allylation of a series of other nueleophiles, as shown in Seheme 1.63, providing the eorresponding allylated produets in moderate enantioseleetivities. 

Scheme 1.63 Test reaction with (5)-proline-derived phosphinyl sulfonamide ligand.

On the other hand, chiral sulfur-containing but noncoordinating ligands such as sulfonamides have been widely used in the asymmetric Michael reaction. In 1997, Sewald et al. reported the use of a series of chiral sulfonamides depicted in Scheme 2.25 in the Cu-catalysed conjugate addition of ZnEt2 to 2-cyclohexenone. Even the use of a stoichiometric amount of catalyst did not allow the enantioselectivity to be higher than 31% ee. 

Scheme 2.26 Cu-catalysed 1,4-additions of Me2CuLi and ZnEt2 to enones with sulfonamide or bis(sulfonamides) ligands.

In the same context, Tomioka et al. have studied the addition of Me2CuLi to chalcone in the presence of another chiral sulfonamide, depicted in Scheme 2.26, which provided the corresponding 1,4-product in a good yield but with a low enantioselectivity (8% ee). In addition, these authors have obtained both moderate yield and enantioselectivity (<28% ee) for the addition of ZnEt2 to 2-cyclohexenone performed in the presence of a chiral bis(sulfonamides) ligand depicted in Scheme 2.26. ... 

In 2004, excellent enantioselectivities of up to 98% ee were obtained by Morimoto et al. by using a phosphine-sulfonamide-containing 1,1 -binaphthyl-based ligand in the enantioselective copper-catalysed conjugate addition of ZnEt2 to several benzylideneacetones (Scheme 2.27). Similar levels of enan-tioselectivity (up to 97% ee) combined with excellent yields (up to 90%) were obtained by Leighton et al. for the copper-catalysed enantioselective addition of various alkylzincs to cyclic enones performed in the presence of other chiral phosphine-sulfonamide ligands (Scheme 2.27). ... 

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). 

A number of other bis(sulfonamides) derived from tran.s-l,2-diaminocyclo-hexane have been developed by several groups and successfully applied to these reactions. Thus, Walsh et al. have reported the use of a series of these ligands in the enantioselective addition of ZnEt2 to benzaldehyde giving excellent enan-tioselectivities, as shown in Scheme 3.39. ... 

The isoborneol-10-sulfonamide unit represents a new type of chiral structure that has been successfully used in different reactions of organometallic addition to aldehydes with excellent results in some cases. In particular, this unique type of ligand has been investigated by Yus and Ramon for the enantioselective... 

Scheme 3.39 7>aw5-l,2-diaminocyclohexane-derived bis(sulfonamides) ligands for addition of ZnEt2 to benzaldehyde. 

Scheme 3.40 3>aw -l,2-diaminocycloliexane-derived bis(sulfonamides) ligands for additions of ZnEt2 to aldehydes. 

Among various amino alcohols used as ligands, derivatives of simple and easily available carbohydrates are only rarely reported and remain underestimated. In this context, a-hydroxy sulfonamides derived from D-glucosa-mine have been used by Bauer et al. for addition of ZnEt2 to aldehydes, providing the corresponding products in high enantioselectivities of up to 97% ee, as shown in Scheme 3.47. ... 

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... 

Scheme 3.65 C2-Symmetric bis(sulfonamides) ligand for alkynylations of aldehydes.

Scheme 4.1 Addition of ZnEt2 to acetophenone with bis(sulfonamides) diol ligands.

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