Stereoselective general approaches

The 1,3-dipolar cycloaddition reactions of nitrile oxides to unsymmetrically substituted norbomenes (243) and to dicyclopentadiene and its derivatives (244) proceed with complete stereoselectivity. The approach of the dipole takes place exclusively from the exo-face of the bicycloheptane moiety, generally... 

Albeit the yields were only low to moderate, these results are of principal importance, as they indicate the possibility of a rather general stereoselective synthetic approach to oligosubstituted spiropentanes (corresponding to the smal-... 

The reaction of 1-arylsulfonylaziridines 217 with dimethylsulfoniumethoxycarbonyl methylide 218 is a fairly general approach for stereoselective synthesis of 1-arylsulfonylazetidines 219 bearing an ethoxycarbonyl functionality (Equation 58) <1995J(P1)2605>. However, the products are obtained in moderate yields. The reaction involves a regioselective transfer of an ethoxycarbonyl-substituted methylene group from the ylide to 1-arylsulfonylaziridines. 

A stereoselective synthesis of (-)-gallocatechin illustrates a general approach to flavan-3-ols. Mitsunobu coupling of a phenol and an epoxyalcohol provides access to a l-aryl-3-bromo-2-hydroxypropyl 2-iodoaryl ether which is cyclised to the flavanol by a halogen-metal exchange (Scheme 13) <06CL1006>. 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

Nucleophilic addition of ester enolates to enantiopure nitrones, followed by cyclization of the resulting hydro-xylamine, is a general approach to isoxazolidin-5-ones and can be applied to the stereoselective synthesis of these heterocycles <2005CRC775>. In some cases, the cyclization occurs spontaneously under the reaction conditions. For example, the addition of the sodium enolate of methyl acetate to chiral nitrone 551 gave directly the isoxazolidin-5-ones 552 in quantitative yield and high ty -diastereoselectivity (Equation 91) <1998CC493>. 

Charette, A B, Cote, B, Stereoselective s3mthesis of all four isomers of coronamic acid a general approach to 3-methanoamino acids, J. Am. Chem. Soc., 117, 12721-12732, 1995. 

In contrast to the various fermentation and bioconversion approaches that have used enzyme stereoselectivity to syntlresize L-phenylalanine as a single isomer, additional methods have been developed that rely on the same stereoselectivity to resolve racemic mixtures of chemically synthesized amino acids. One such general approach, which has been successfully commercialized for L-phenylalanine production, relies on cleavage of the L-isomer of a D,L-a-amino acid amide mixture by an enantiospecific amidase enzyme. The general procedure operated... 

There are three general approaches to oligosaccharide preparation. The first approach is the isolation of the desired compound from its natural source. This is, however, a very laborious and time-consuming method and may yield only small quantities of the desired product. The second and most well-established approach is to use chemical synthesis. There are a variety of methods available, but the synthesis is also time-consuming and requires much expertise. Multiple protection and deprotection steps for both donor and acceptor components are necessary to ensure desired regio-and stereoselectivity. 

On the Mechanism of Stereoselection in Rh-Catalyzed Asymmetric Hydrogenation A General Approach for Predicting the Sense of Enantioselectivity ... 

A more general approach concentrates on the chiral modification of the carbene ligand. Some examples based on a chiral carbene carbon side chain are depicted in Figure 4. [68] The reaction of alkoxy- and amino(cyclohexenyl)carbene complexes with 1 -pentyne afforded diastereomeric tetralin complexes in moderate yields. [69] The sense of stereoselection was found to depend on the substitution pattern of the cyclohexenyl substituent. Whereas 5-methyltetralin derivatives were obtained in low preference for the syn complex, a higher preference for the anti diastereomer was observed synthesizing the 8-methyltetralin complexes 50 (Scheme 27). [69]... 

In the 1990s, Tingoli and coworkers developed a general approach to various arylselenated products by the reaction of unsaturated compounds with diaryl diselenides and (diacetoxyiodo)benzene [600-603]. Various phenylselenated products are formed in good yields from the reaction of alkenes with diphenyl diselenide and (diacetoxyiodo)benzene in acetonitrile. In particular, cyclohexene under these conditions stereoselectively affords fra i -l-acetoxy-2-(phenylseleno)cyclohexane (541) in good yield (Scheme 3.214) [603]. 

A general approach for the synthesis of symmetrical and unsymmetrical diketopiperazines from unprotected amino acids has been published by Brdse et al. in 2007 (418) (Scheme 10.7). The phosphorus-promoted coupling method developed is a stereoselective one-pot synthesis that works either by conventional heating or in a microwave-assisted way (419). The suitability of this method for... 

Scheme 4.49 General approaches of stereoselective hydroformylation of mono-substituted terminal olefins.

Gridnev, I. D. Imamoto, T. On the mechanism of stereoselection in Rh-catalyzed Asymmetric hydrogenation A general approach for predicting the sense of enantioselectivity. Acc. Chem. Res. 2004,37,633-644. 

Some studies on Meyer s route to chiral carboxylic acids (1, 1 2, 10) have revealed that stereoselectivity in the deprotonation of chiral oxazolines is very dependent on the particular base-solvent combination used. A further route to chiral acids is by alkylation (with primary halides) and subsequent hydrolysis of the bis-anionic species (1) derived from acid anhydrides and /-ephedrine. Chemical yields are in the range 50—70%, while optical yields are around 75%. A full report has appeared on the general approach to chiral acids by the Michael addition of Grignard reagents to oxazepinedione derivatives (2), also derived from /-ephedrine. Optical yields of 80—99% have been claimed (2,11 3, 27). 

Tripathi, D., Kumar Pandey, S., and Kumai P. (2009) A general approach to medium-sized ring ethers via hydrolytic and oxidative kinetic resolutions stereoselective syntheses of ( )-cis-lauthisan and (+)-isolaurepan. Tetrahedron, 65, 2226-2231. 

In the early days of asymmetric synthesis, the stereoselective reduction of olefins as a general approach to optically active building blocks was rather limited to the preparation of non-natural amino acids (Chapter 10). Indeed, asymmetric transformations of olefins were much more general for oxidation (Chapter 9) and hydroboration processes (Chapter 7). As discussed in this chapter, such limitations are no longer the case. The stereoselective reduction of alkenes can be a viable and reliable transformation for the construction of multiple classes of optically active building blocks. Moreover, the efficiencies and selectivities often observed with these reactions represent a gold standard to which the myriad of other asymmetric transformations are compared. 

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