Chiral sulfonamide esters

Since the last review in this series in 1993 (10) and the publication of Ojima s paper summarizing his approach to the / -lactam (237), a number of new approaches for the asymmetric synthesis of the / -lactam taxol side chain have emerged. For example, chiral sulfonamide esters have been used as chiral auxiliaries to achieve diastereoselective cycloaddition with N-TMS-imine, to give lactam 7.1.1 in 94% yield. Benzoylation of 7.1.1 yielded the ready-to-couple lactam 7.1.2 in 96% yield (238). 

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). 

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... 

Poor (<4% de) to modest (56% de) amounts of diastereofacial selection is observed in the cycloaddition of nitrile oxides to optically active acrylates. The plan in each case, of course, was to use a chiral auxiliary which would preferentially shield one of the two ir-faces of the dipolarophile. Of the auxiliaries used, the sulfonamide esters derived from (+)-camphorsulfonyl chloride worked best, the menthyl esters derived from (-)-menthol the poorest (<4% de). As illustrated in Table 19, changes in both temperature and solvent had either no or little affect on the product ratios. Unlike Diels-Alder reactions, the addition of Lewis acids, specifically Et2AlCl, EtAlCh and TiCL, resulted in significant decreases in both the rate of cycloaddition and isolated yield, without an appreciable change in diastereomer ratio. ... 

Pd-catalyzed cyclization was also applied to the stereocontrolled preparation of chiral substituted tetrahydrofurans. The synthesis of optically active tetrahydrofurans was pioneered by Stork and Poirier,who described effective chirality transfer in the Pd-assisted cyclization of y-hydroxy allylic esters. Williams and Meyer deployed a variant of the 0-capture of 7r-allylpalladium complexes in the reactions of substimted trimethylenemethane palladium complexes developed by Trost, using aUylstannane (Scheme 32). A key intermediate 156 in the synthesis of amphidinolide K, a marine nam-ral product, was therefore synthesized starting from enantiopure diastereomer 160. Compound 160 was prepared by in situ transmetallation using the Corey chiral sulfonamide 159 with optically active aUylstannane 157 and then condensation with functionalized aldehyde 158. Formation of the c -2,5-disubstituted tetrahydrofuran 156 occurred with an excellent diastereoselectivity (cis/trans 13 1) and a good yield (88%) from the syn-1,4-precursor 160. 

W. Wang, M.-H. Xu, X.-S. Lei, G.-Q. Hn, Chiral sulfonamide induced enantioselective protonation of samarium enolate in the reaction of a,p-unsaturated ester with ketone, Org. Lett. 2 (2000) 3773-3776. 

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. 

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... 

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. 

Camphorsulfonyl chloride has been widely used as a chiral deriva-tizing agent for the assay of enantiomeric purity of alcohols and amines by NMR techniques. A typical procedure for the preparation of the sulfonate ester or sulfonamide involves mixing a solution of the alcohol or amine in CH2CI2 with camphorsulfonyl chloride in the presence of an amine base (EtsN, py, or DMAP). This reagent has been particularly valuable for determining the enantiomeric purity of secondary alcohols (1, 2) and p-hydroxy esters (3). ... 

From the optimisation of the above compounds, potent nonpeptidic benzimidazole sulfonamide inhibitors were disclosed [57]. The synthesis followed the route previously depicted. The ester 171b was reduced and deprotected giving 175 in high yield and its coupUng with substituted phenylendiamine 176 followed by cyclisation under acidic conditions afforded the desired benzimidazole 177. Careful control of the temperature was critical because ring closure at higher temperatures proceeded more rapidly but returned mixtures of diastereomers at the a-centre of the amino acid. The (R/S)-1ZD diastere-omers were easily separated by chiral HPLC to afford two discrete isomers. Both diastereomers were further elaborated to the final compounds providing... 

Enantiopure P-alkoxyalcohols have also been used as chiral auxiliaries. Among the most useful auxiliaries in this class are the acyclic methylether 1.11 [148] or silylether 1.12 [149, 150], and the cyclic monobenzyl- or neopentylethers 1.13 (R = PhCH2 or tert-BuCH2) derived from exo-bomane-2,3-diols [147], From inexpensive, commercially available ephedrine, (li , 2S)-Af-methylephedrine 1.14 is easily obtained, its (15,2R)-enantiomer is easily available too. The esters of these alcohols [151-154] have frequently been used. Among the cyclic alcohols, sulfonamide derivatives 1.8 and 1.9 (R = NHS02Ar or N(Ar)S02Ph) are especially useful [147,155],... 

Until recently, little success had been achieved in developing a highly enantioselective version of the Darzens reaction. Several investigations of chiral phase-transfer catalysts for this condensation, in which low or modest asymmetric induction is obtained, have been reported. These include the use of N-alky -N-methylephedrinium halides, the quinine-derived salt (120), and polyamino acids. A related study has examined the use of achiral phase-transfer catalysts in the condensations of carbonyl compounds and the asymmetric chloromethylsulfonate ester (121). The same group of researchers subsequently reported similar studies employing the sulfonamides (122)-(124). ... 

Assorted anions. These are generated by deprotonation of allylic halides," chloromethylphosphonic esters, conjugated hydrazones, chiral carbamates,unsaturated a-aminonitriles, phosphonamides," and sulfonamides. The dianions derived from tu-haloalkanecarboxylic acids cyclize, and this reaction forms the basis of a synthesis of V-Boc cyclic imino acids. The conjugate bases of 2-(arylmethoxy)-methyl-2-oxazolines are unstable as [2,3]sigmatropic rearrangement takes place even at — 75°C. 

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