Chirality chiral sulfonamides

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. ... 

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... 

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... 

Nagao has disclosed bifunctional chiral sulfonamide 69 as being effective for the thiolytic ASD of meso-cyclic anhydrides in up to 98% ee when employed at the 5 mol% level for 20 h at room temperature in ether [228], Catalyst 69 is a 1,2-diamine derivative in which one of the nitrogens presents as an acidic NH group (part of an electron deficient aryl sulfonamide) and the other as a nucleophihc/basic teri-amine group with the intention to act synergistically in activation of the substrate carbonyl function and thiol nucleophile respectively (Fig. 16) [228],... 

Polymer-supported chiral sulfonamide catalyzed reduction... 

POLYMER-SUPPORTED CHIRAL SULFONAMIDE CATALYZED REDUCTION OF j -KETO NITRILES A PRACTICAL SYNTHESIS OF (R)-FLUOXETINE... 

Enantioselective reduction of jS-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane-dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity (Figure 3.11). The facile and enantioselective method to prepare optically active 1,3-amino alcohols has been used to prepare 3-aryloxy-3-arylpropylamine type antidepressant drugs, for example (l )-fluoxetine. 

Polymer-supported chiral sulfonamide (loading = 2.36mmol g ), (127mg, 0.30 mmol)... 

To polymer-supported chiral sulfonamide (127 mg, 0.3 mmol) in a 50 mL threenecked flask, was added 15mL dry THF and 1.6 mL borane-dimethyl sulfide complex under an argon atmosphere. The suspension was heated under reflux and stirred for 0.5 h. 

Figure 29. Synthesis of macrocycle 65 and the corresponding, topologically chiral sulfonamide catenane 79.

Asymmetric cyclopropanation of olefins can also be achieved by the Simmons-Smith reaction (231). Reaction of ( )-cinnamyl alcohol and the diiodomethane-diethylzinc mixed reagent in the presence of a small amount of a chiral sulfonamide gives the cyclopropylcarbinol in up to 75% ee (Scheme 97) (232a). ( )-Cinnamyl alcohol can be cyclopro-... 

In other diethylzinc studies, a neural network modelling approach has been used to predict the utility of new enantioselective catalysts,222 norephedrine-derived ligands with three stereogenic centres catalyse enantioselective addition to aldehydes and to chalcones,223 and a chiral sulfonamide ligand based on tartaric acid gives good ees in addition to both aldehydes and ketones.224... 

Diastereoselective Mannich-type reactions between ketene silyl acetals and chiral sulfinimines using simple metal-free Lewis bases such as tetraalkylammonium car-boxylates have been reported. The sulfinimine can even be generated in situ (from aldehyde and a chiral sulfonamide), using cesium carbonate, followed by addition of ketene silyl acetal at -78 °C, and as little as 1 mol% of catalyst.32... 

Add a solution of the chiral sulfonamide and ( )-5-phenyl-2-penten-1-ol in dichloromethane (200 mL) at room temperature. 

Ghosh also took advantage of the C—2 hydroxyl moiety of aminoindanols as a handle in the aldol reaction. Chiral sulfonamide 41 was O-acylated to give ester 42. The titanium enolate of ester 42 was formed as a single isomer and added to a solution of aldehyde, precomplexed with titanium tetrachloride, to yield the anft -aldol product 43 in excellent diastereoselectivities.63 One additional advantage of the ester-derived chiral auxiliaries was their ease of removal under mild conditions. Thus, hydrolysis of 43 afforded a ft -a-methyl- 3-hydroxy acid 44 as a pure enantiomer and cis-1-/ -1 o I y I s u I f on a m i do- 2 - i n da n ol was recovered without loss of optical purity (Scheme 24.7).63... 

As discussed in Section III J, in general, catalytic asymmetric aldol reactions have been studied using enol silyl ethers, enol methyl ethers, or ketene silyl acetals as a starting material. So far several types of chiral catalysis have been reported.75-85 The chiral lanthanoid complex prepared from Ln(OTf)3 and a chiral sulfonamide ligand was effective in promoting an asymmetric Mukaiyama aldol reaction with a ketene silyl acetal.86 The preparation of the catalyst and a representative reaction are shown in Figure 45. 

Surprisingly few studies have been directed towards the development of noncinchona alkaloid-based catalysts for the alcoholative ASD of meso-anhydrides, or indeed any of the enantioselective alcoholysis processes. Uozumi has reported a series of (2S, 4R)-4-hydroxyproline-derived 2-aryl-6-hydroxyhexahydro-lfi-pyr-rolo[l,2-c] imidazolones which mediate the methanolytic ASD of ds-hexa-hydrophthalic anhydride in up to 89% ee when employed at the 10 mol% level for 20 h at —25 °C in toluene [186]. Additionally, Nagao has described the use of a bifunctional chiral sulfonamide for the thiolytic ASD of meso-cyclic anhydrides in up to 98% ee when employed at the 5 mol% level for 20 h at rt in ether [187]. 

The chiral sulfonamide 45, which can be prepared in two steps from commercially available (I R,2S)-cis-1 -amino-2-indanol (44), was introduced by Ghosh and Onishi for the synthesis of enantiomerically pure anft -aldol products via titanium enolate19a (Scheme 2.2q). 

Diels-Alder Reactions. Reaction of the bis(triflamide) (2) with Diisobutylaluminum Hydride or Trimethylaluminum affords chiral Lewis acids that catalyze Diels-Alder reactions of acryloyl or crotonoyl derivatives with cyclopentadienes (eq 4). The aluminum complex must be crystallized before use to remove traces of trimethylaluminum. High diastereo- and enantioselectivities are achieved with as little as 0.1 equiv of the Lewis acid, and the chiral sulfonamide is recoverable. 

Mukaiyama aldol reactions are useful means of constructing complex molecules for the total synthesis of natural products. Although catalytic asymmetric Mukaiyama aldol reactions have been achieved by use of a variety of chiral Lewis acids [42], no report of the use of chiral lanthanide catalysts was available until recently, despite the potency of these catalysts. Shibasaki and co-workers reported the first examples of chiral induction with chiral lanthanide complexes (Sch. 7) [43]. Catalysts prepared from lanthanide triflates and a chiral sulfonamide ligand afforded the corresponding aldol products in moderate enantiomeric excess (up to 49% ee). 

Based on the reaction of diorganozinc with cycloalkenone catalyzed by N-monosubstituted sulfonamide and copper(I) [69], the effect of chiral sulfonamide 33 was examined. It was found that catalytic amounts of both sulfonamide and copper(I) are necessary to catalyze the reaction, but ee was at most 32% [70]. 

The catalyst was synthesized from borane dimethyl sulfide and a chiral polymer 103 bearing N-sulfonylamino acid groups. The latter was prepared by co-polymerization of chiral sulfonamide 104 with styrene 58 and the cross-linking agent 105 in the presence of benzoyl peroxide as a radical initiator. 

Polymer-supported chiral sulfonamides also proved to be efficient catalysts for the enantioselective reduction of P-keto-nitriles [54]. This was demonstrated in the synthesis of anti-depressant drugs -fluoxetine 43 and -duloxetine (Scheme 4.11). 

Scheme 4.10 Asymmetric reduction using polymer-supported chiral sulfonamide 39.

Asymmetric a-alkylation of amines was achieved applying an immobilized chiral sulfonamide (Scheme 12.29) [13, 40]. To synthesize auxiliary 76, a tertiary alcohol (73) was converted into Grignard reagent 74. Addition of sulfur dioxide and subsequent chlorination furnished the sulfinyl chloride 75. Reaction with (S)-2-amino-l,l,2-triphenylethanol, followed by reduction, hydroboration and... 

Scheme 12.29 Synthesis and application of a polymer supported chiral sulfonamide.

CrCl2/NiCl2(dppp), Mn, LiCl chiral sulfonamide, MeCN Namba. K. Kishi. Y. Org. Lett.2004, 6, 5031. 

---