Chiral Sulfonamides

Besides sulfonamides, chiral sulfoximines have also been used in C - N bond formation under microwave irradiation [103]. The only heteroaryl chloride used in the study—namely, 2-chloropyridine—gave the desired M-(pyridin-2-yl)sulfoximine at a yield of 43% (Scheme 101). Interestingly,... 

Chiral boron(III) complexes can catalyze the cycloaddition reaction of glyoxy-lates with Danishefsky s diene (Scheme 4.18) [27]. Two classes of chiral boron catalyst were tested, the / -amino alcohol-derived complex 18 and bis-sulfonamide complexes. The former catalyst gave the best results for the reaction of methyl glyoxylate 4b with diene 2a the cycloaddition product 6b was isolated in 69% yield and 94% ee, while the chiral bis-sulfonamide boron complex resulted in only... 

Only one example, showing high stereoselectivity, is known in this class of reactions. On treatment of the acyclic glycine cation equivalent 1 (see Appendix), containing the ( + )-cam-phor-10-sulfonamide ester as a chiral auxiliary, with boron trifluoridc and anisole at 0"C a mixture of aromatic substitution products is obtained in essentially quantitative yield 55. Besides 11 % of cuV/io-substitution product, the mixture contains (R,S)-2 and its (/ ,/ )-epimer in a ratio >96 4 (NMR). The same stereoisomer 2 predominates when the reaction is conducted in sulfuric acid/acetic acid 1 9, although the selectivity is slightly lower (91 9 besides 25% of ortho substitution). 

Optically active bicyclo[2.2,2]octanes can be obtained via diastercoselective MIMIRC reaction of lithium dienolates and a,/ -unsaturated esters of various chiral alcohols. Good yields (70-90%), high endo selectivities (> 95%) and diastereomeric ratios that depend on the auxiliary alcohol are found in these additions. The highest diastereomeric ratio reached was 18 82 using a camphor derived sulfonamide. The diastereomeric ratio could be improved (up to 9 91) by titanium(IV) chloride catalyzed addition of the corresponding silylenolates with the chiral a,/J-unsaturated esters358. 

Deming T.J., Facile synthesis of block copol3fpeptides of defined architecture. Nature, 390, 386, 1997. Seidel S.W. and Deming T.J., Use of chiral mthenium and iridium amido-sulfonamidate complexes for controlled, enantioselective polypeptide synthesis. Macromolecules, 36, 969, 2003. 

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-... 

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. 

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. 

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). 

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... 

On the other hand, several examples of chiral sulfonamides derived from ehiral a-amino acids have been successfully employed as ligands for enantio-seleetive Diels-Alder reactions. Thus, Yamamoto and Takasu have easily prepared new chiral Lewis acids from borane and sulfonamides of various ehiral a-amino acids, which were further studied for their abilities to promote the enantioselective Diels-Alder reaction between methacrolein and 2,3-dime-thyl-1,3-butadiene. Since 2,4,6-triisopropylbenzenesulfonamide of a-amino-butyric acid gave the highest enantioseleetivity, this eatalyst was applied to the... 

Several catalytic systems have been reported for the enantioselective Simmons Smith cyclopropanation reaction and, among these, only a few could be used in catalytic amounts. Chiral bis(sulfonamides) derived from cyclo-hexanediamine have been successfully employed as promoters of the enantioselective Simmons-Smith cyclopropanation of a series of allylic alcohols. Excellent results in terms of both yield and stereoselectivity were obtained even with disubstituted allylic alcohols, as shown in Scheme 6.20. Moreover, this methodology could be applied to the cyclopropanation of stannyl and silyl-substituted allylic alcohols, providing an entry to the enantioselective route to stannyl- and silyl-substituted cyclopropanes of potential synthetic intermediates. On the other hand, it must be noted that the presence of a methyl substituent at the 2-position of the allylic alcohol was not well tolerated and led to slow reactions and poor enantioselectivities (ee<50% ee). ... 

The existence of ketenes was established over a hundred years ago, and, in recent years, asymmetric synthesis based on [2 + 2] cycloadditions of ketenes with carbonyl compounds to form chiral p-lactones has been achieved with high yields and high stereoselectivities. In 1994, Miyano et al. reported the use of Ca-symmetric bis(sulfonamides) as ligands of trialkylaluminum complexes to promote the asymmetric [2 + 2] cycloaddition of ketenes with aldehydes. The corresponding oxetanones were obtained in good yields and enantioselectivities... 

Asymmetric Mukaiyama aldol reactions have also been performed in the presence of Lewis-acid lanthanoid complexes combined with a chiral sulfonamide ligand. Similar enantioselectivities of about 40% ee were obtained for all... 

Derivatives with various substituted sulfonamides have been developed and used to form enolates from esters and thioesters.137 An additional feature of this chiral auxiliary is the ability to select for syn or anti products, depending upon choice of reagents and reaction conditions. The reactions proceed through an acyclic TS, and diastereoselectivity is determined by whether the E- or Z-enolate is formed.138 /-Butyl esters give A-enolates and anti adducts, whereas phenylthiol esters give syn adducts.136... 

Camphor-derived sulfonamide can also permit control of enantioselectivity by use of additional Lewis acid. These chiral auxiliaries can be used under conditions in which either cyclic or noncyclic TSs are involved. This frequently allows control of the syn or anti stereoselectivity.143 The boron enolates give syn products, but inclusion of SnCl4 or TiCl4 gave excellent selectivity for anti products and high enantioselectivity for a range of aldehydes.145... 

The use of metal-catalyzed aziridination methods with chiral ligands has also been reported. The copper-based system paired with ligand 56 provides the expected cinnamyl aziridine in good yield and excellent ee <06MI4568>. It is interesting to note that the /-butyl ester is obtained with 99% ee while the smaller methyl ester is obtained in only 88% ee. The binaphthyl ruthenium catalyst 57 has been found to aziridinate a number of olefins with moderate enantioselectivity <06TL1571>. Both p-nitrophenyl (Ns) and trimethylsilyloxy (SES) sulfonamides work well with this catalytic system. As is usually seen, the aziridination of aliphatic olefins proceeds in only 32% yield and 56% ee. 

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