Stereoselective Approaches

Early efforts to control P/ stereochemical identity with only modest efficiency included enzymatic hydrolysis of C-terminal methyl carboxylates [18] and 

The second and most important reason for pursuing post-modification is the possibility of widely diversifying pseudopeptide side chains at a late stage in the synthesis, thus enhancing screening options in medicinal projects. In an extension of an older report by Schoen and Parsons [49], Matziari et al. prepared a series of dehydroalanine pseudodipeptides by allylic displacement of 2-bromomethyl acrylate from aminophosphinic acid, and tested their reactivity in conjugate additions of 

An interesting approach to this direction was recently based on an Ireland-Claisen rearrangement triggered by the phospha-Michael addition of silyl 

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The intriguing structural complexity and often potent biological activity exhibited by many polyacetate-derived natural products have generated a continuing interest in the development of efficient, stereoselective approaches to the assembly of repeating l -diol subunits. One such method is the alkylation and reduc-... 

Wolberg, M., Hummel, W. and Muller, M. (2001) Biocatalytic reduction of beta,delta-diketo esters a highly stereoselective approach to all four stereoisomers of a chlorinated beta,delta-dihydroxy hexanoate. Chemistry -A European Journal, 7 (21), 4562-4571. 

Nucleophilic addition of lithiated sulfones to nitrones made it possible to develop new stereoselective approaches to the synthesis of pyrrolidine-N -oxides based on a reverse-Cope-type elimination. One method is based on the reaction of lithiated sulfones with nitrones (386) (Scheme 2.168) (625). 

Thus far, most of the stereoselective approaches to aldol reactions mentioned have depended on substrate-based asymmetric induction by employing chiral... 

The purpose of this study was to explore the introduction of an OZT moiety onto the specific C-3 site of both l,2 5,6-di-0-isopropylidene-a-D-glucofuranose and 1,2 4,5-di-0-isopropylidene-p-D-fructopyranose, taking advantage of the well-defined frame of both carbohydrate structures to generate all possible OZT-isomers. These spiroheterocyclic structures could be constructed according to a simplified sequence based on a key stereoselective approach from uloses via epoxides or aziridines (Scheme 16). 

In a study which was conducted simultaneously to the work in the Mehta group and which also aimed to prove the absolute configuration of natural kelsoene (1), Schulz et al. used a stereoselective approach starting from the enantiomerically pure chiral pool material (i )-pulegone 17 [9, 10] (see above). The final steps of their synthesis of the unnatural enantiomer of kelsoene (ent-l) were similar to the above-described first total synthesis of natural kelsoene (1) (Scheme 8). Taking into account the steric limitations of the system as communicated by Srinivas and Mehta, diquinane enone ent-6... 

Subsequent synthetic literature around duloxetine (3) is focused around the description of stereoselective approaches to the critical alcohol intermediate 36, or similar derivatives. 

Reactions of propynyl alcohols and their derivatives with metal hydrides, such as lithium aluminum hydride, constitute an important regio- and stereoselective approach to chiral allenes of high enantiomeric purity63-69. Formally, a hydride is introduced by net 1,3-substitution, however, when leaving groups such as amines, sulfonates and tetrahydropyranyloxy are involved, it has been established that the reaction proceeds by successive trans-1,2-addition and preferred anti-1,2-elimination reactions. The conformational mobility of the intermediate results in both syn- and ami- 1,2-elimination, which leads to competition between overall syn- and anti-1,3-substitution and hence lower optical yields and/or a reversal of the stereochemistry. 

In summary, the procedure described in this chapter is representative of a very general, highly stereoselective approach to trisubstituted alkenes. The usefulness of this methodology has already been demonstrated in total synthesis. M e,f, h,k,13... 

G. Casiraghi, F. Zanardi, G. Rassu, and P. Spanu, Stereoselective approaches to bioactive carbohydrates and alkaloids—With a focus on recent syntheses drawing from the chiral pool, Chem. Rev. 95 1677 (1995). 

V. Pedretti, J. M. Mallet, and P. Sinay, Silylmethylene radical cyclization—a stereoselective approach to branched sugars, Carbohydr. Res. 244 241 (1993). 

The Cope rearrangement of c/j-di vinylcyclopropanes is thermally allowed and offers an attractive stereoselective approach to cycloheptadienes. Cyclopropanation reactions can be used to prepare divi-nylcyclopropanes, as shown in Scheme 23.120 Reaction of ethyl diazopyruvate with butadiene generated... 

Transformations shown in Schemes 12-14 constitute the first examples of catalytic AROM reactions ever reported. Meso-triene 50 is converted to chiral heterocyclic triene 32 in 92% ee and 68% yield in the presence of 5 mol % 4a (Scheme 12) [21]. Presumably, stereoselective approach of the more reactive cy-clobutenyl alkene in the manner shown in Scheme 12 (II) leads to the enantioselective formation of Mo-alkylidene III, which in turns reacts with an adjacent terminal olefin to deliver 51. Another example in Scheme 12 involves the net rearrangement of meso-bicycle 52 to bicyclic structure 54 in 92% ee and 85% yield. The reaction is promoted by 5 mol % 4a and requires the presence of di-... 

The domino re-cationic cyclization popularized by Johnson and co-workers has provided a powerful stereoselective approach to the steroid subfamily of terpenoids [27]. This pioneering biomimetic work established that the entire carbocydic... 

It is possible to isolate the intermediate of the first step in the tandem MCI reaction, when the reaction was carried under acidic conditions [Eq. (110)]. This method provides a convenient and stereoselective approach to jS-functionalized (Z)-alkenyl-A3-iodanes 125, because Michael addition proceeds in an exclusively stereoselective manner. Thus, (Z)-/ -sulfonyl [170], (Z)-/J-halo [195], (Z)-/J-acetoxy [196], and (Z)-/J-azidoalkenyl-A3-iodanes [197] were synthesized stere-oselectively in high yields. These results provide firm evidence for the tandem MCI pathway. 

Carrying out the benzhydrylpiperazine formation via nucleophilic displacement as depicted in Scheme 2 using the enantiopure (—)-(2R,5S)-l -allyl-2,5-dimethylpiperazine provides two stereoisomers, epimeric at the benz-hydryl position. These epimers are separable by common chromatographic techniques (although these are sometimes difficult separations), and the absolute stereochemistry of the products has been proven via x-ray crystallography [19,23,40,41]. For large-scale preparation, a stereoselective approach to the final products is preferred to minimize waste and reduce costs. Two distinct stereoselective routes to benzhydrylpiperazines have been described. 

Singh, V., Praveena, G.D., Karki, K., and Mobin, S.M. (2007) Cydoaddition of cydohexa-2,4-dienones, ring-closing metathesis, and photochemical reactions a common stereoselective approach to duprezianane, polyquinane and... 

In combination with the range of standard transformations of alcohols, alkenes, and vinylsulfides, these silicon-tethered additions of functionalized radicals offer a versatile and stereoselective approach to amino alcohol synthesis. Whereas vinyl and 2-oxoethyl radicals have not yet been demonstrated as competent participants in the various intermolecular additions reported in the literature, the temporary tether approach allows such functionalized fragments to be installed in an efficient and stereoselective manner. Synthesis of the aminosugar daunosamine from achiral precursors shows how this concept, employing hydrazone radical acceptors, can be merged with asymmetric catalysis to achieve practical synthetic advances. 

The reactions of vinyl(tri-n-butyl)stannanes with the appropriate [cyano(sulfonyloxy)-iodo]benzenes in dichloromethane constitute a facile stereoselective approach to / ,/ -disubstituted vinyl(phenyl)iodonium tosylates and triflates (equation 168)130,131. Although this method has not yet been used for the preparation of a,/ -disubstituted and a,/ ,/ -trisub-stituted analogs, it has been applied to the synthesis of ethenyl(phenyl)iodonium triflate131. The efficiency of this approach may be contrasted with the early work on chlorostannanes and chloroiodanes. 

Stereoselective enolate bromination as an approach to a-halo carboxylic acids and a-aminoketones.32 a-Haloketones are useful synthetic intermediates,33 and may be derived from enolates by treatment with sources of electrophilic halide. This methodology has been applied by others34,35 as a stereoselective approach to chiral a-aminoacids. 

Following the same principle Fiandanese and coworkers [111] have developed an efficient stereoselective approach to silylated polyunsaturated y-alkylidene butenolides 143-145 starting from Z-3-iodo-propenoic acid (Scheme 55). 

A new stereoselective approach to isoxazolidines through Pd-catalyzed carboetherification reactions of unsaturated hydroxylamines was described. V-(3-Butenyl)hydroxylamines were reacted... 

Denis, J.-N. Fkyerat, A. Gimber, Y. Coutterez, C. Mantellier, R Jost, C. Greene, A. E. Docetaxel (Taxotere) derivatives novel NbCls-based stereoselective approach to 2 -methylated docetaxel. J. Chem. Soc. Perkin Trans. 1, 1995, 1811-1816. 

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