Stereoisomerism Stereochemistry Stereoisomers

Steam distillation, 3290, 3667, 3978,4090 Stearidonic acid, 1737 Steatosis, 1385 Stegobium paniceum, 4091 Stemmedine, 584 Stemona, 1175 Stemona alkaloids, 1183 Stephaniae tetrandrae, 1179 Stephania tetrandra S. Moore, 1449 Stephanine, 431 Stephanitis pyri, 4094 Stepholidine, 449 Sterculiaceae, 725 Stereocenters, 947 Stereochemistry, 3241, 3242 Stereoisomerism, 1014 Stereoisomers, 912, 2109, 3647 Stereospecific conversion, 1670 Stereospecificity, 4069 Steroidal, 412 alkaloids, 3237 lactones, 3468, 3473, 3488 Steroid hormone receptors, 3508 Steroids, 2733-2735, 2737-2741, 2746-2749, 2751, 2753, 2755-2757, 2763, 3666, 3670... 

Vinyl radicals can also participate in 6-exo cyclizations. In pioneering work, Stork and his group at Columbia University showed that stereoisomeric vinyl bromides 20 and 21 (see Scheme 3) can be converted to cyclohexene 22.7 The significance of this finding is twofold first, the stereochemistry of the vinyl bromide is inconsequential since both stereoisomers converge upon the same product and second, the radical cyclization process tolerates electrophilic methoxycarbonyl groups. The observation that the stereochemistry of the vinyl bromide is inconsequential is not surprising because the barrier for inversion of most vinyl radicals is very low.8 This important feature of vinyl radical cyclization chemistry is also exemplified in the conversion of vinyl bromide 23 to tricycle 24, the key step in Stork s synthesis of norseychellanone (25) (see Scheme 4).9 As in... 

The dissection of a molecular model into those components that are deemed to be essential for the understanding of the stereochemistry of the whole may be termed factorization (9). The first and most important step toward this goal was taken by van t Hoff and Le Bel when they introduced the concept of the asymmetric carbon atom (10a, 1 la) and discussed the achiral stereoisomerism of the olefins (10b,lib). We need such factorization not only for the enumeration and description of possible stereoisomers, important as these objectives are, but also, as we have seen, for the understanding of stereoselective reactions. More subtle differences also giving rise to differences in reactivity with chiral reagents, but referable to products of a different factorization, will be taken up in Sect. IX. 

For an unsymmetrical dienophile, there are two possible stereochemical orientations with respect to the diene. The two possible orientations are called endo and exo, as illustrated in Fig. 6.3. In the endo transition state, the reference substituent on the dienophile is oriented toward the % orbitals of the diene. In the exo transition state, the substituent is oriented away from the % system. For many substituted butadiene derivatives, the two transition states lead to two different stereoisomeric products. The endo mode of addition is usually preferred when an electron-attracting substituent such as a carbonyl group is present on the dienophile. The empirical statement which describes this preference is called the Alder rule. Frequently, a mixture of both stereoisomers is formed, and sometimes the exo product predominates, but the Alder rule is a useful initial guide to prediction of the stereochemistry of a Diels-Alder reaction. The endo product is often the more sterically congested. The preference for the endo transition state... 

Cis and trans isomers are only one type of stereoisomerism. The study of the structure and chemistry of stereoisomers is called stereochemistry. We will encounter stereochemistry throughout our study of organic chemistry, and Chapter 5 is devoted entirely to this field. 

In the hydrodimerization of 2,3-dimethylindanone, 11 hydrodimers, including 8 stereoisomers, were analyzed [150]. The stereochemistry of hydrodimers formed from 2-methylindenone in an oxygen-saturated DMF solution would also be complicated, but it is known only that the stereochemistry around the central C-C bond is a threo form [151]. Another complication in the stereochemistry of a hydrodimer was observed in the dimerization of benzoin at a mercury-plated copper cathode in a basic aqueous ethanol solution A single stereoisomeric hydrodimer was formed [152]. 

One aspect of stereochemistry is stereoisomerism. Isomers, we recall, are different compounds that have the same molecular formula. The particular kind of isomers that are different from each other only in the way the atoms are oriented in space (but are like one another with respect to which atoms are joined to which other atoms) are called stereoisomers. 

It is of paramount importance to look for stereochemistry-related compounds, i.e., those compounds that have similar chemical structure but different spatial orientation. These compounds can be considered impurities in the API. Included in this group are various stereoisomers. The simplest case of chirality can be seen in a molecule that has one or more tetrahedral carbons with four different substituents (asymmetric carbon atom) such that its mirror image is not superimposable. Chiral molecules may also occur for a number of other reasons and must be factored into any evaluation of impurities.10-12 Stereoisomerism is possible in molecules that have any of the following characteristics ... 

In this section we discuss relationships between reactivity and stereochemistry. Many reactions can produce two or more stereoisomeric products. If a reaction shows a preference for one of the stereoisomers, it is stereoselective. Throughout the sections on individual reactions in Parts A and B, we discuss the stereoselectivity associated with particular reactions. In this chapter, we use a few examples to illustrate the fundamental concepts of stereoselectivity. 

The stereochemical outcome of this oligoselective polymerization is of some interest. In principle, eight stereoisomeric macrocycles 94 can be formed. However, HPLC analysis of the cyclized material revealed that only six of these possibilities are represented in the product mixture. In benzene as solvent, over half of the product mixture is a single stereoisomer, whereas in methyl isobutyrate as solvent the diastereomers are more evenly distributed. Preliminaty attempts to ascertain the relative stereochemistry of the major isomer within 94 via DNOE NMR measurements did not allow unambiguous assignment. Without this structural information in hand, further speculation on the relationship between chain stereochemistry and cyclization efficiency within 99 (see Scheme 8-27) is not warranted. Nevertheless, there must be some influence, given the non-statistical distribution of isomers. In comparison, the H-NMR spectrum of the pMMA portion of uncontrolled oligomer 95 is superimposable with that of atactic (i.e., random stereochemistry) pMMA. 

It is of interest that the optical rotations of FTF, FTH, and FTL are opposite (levorotary) to those of FTJ, FTE, and FTG (dextrorotary), respectively, though their chemical structures are identical except for the stereochemistry at C-12. Yamazaki et al. (156) found that FTF, FTH, and FTL are obtained upon treatment of FTJ, FTE, and FTG, respectively, with 0.1% KOH in MeOH. This fact indicates that the metabolites of the former group are the C-12 stereoisomers of the latter group (S configuration), respectively. The possibility that the compounds identified as FTF, FTH, and FTL are artifacts remain. FTM (89) is also obtained from nortryptoquivaline by the KOH-MeOH reaction, demonstrating their stereoisomerism. 

The formation of the aforementioned compounds proceeds with remarkable selectivity. Only one stereoisomer has been identified for each constitutionally different "mono telomer (14, n = 1), whereas for compounds with n = 2 and = 3, two and four stereoisomeric compounds have been isolated, respectively. It has been assumed that trans addition to 6 is strongly favored under the conditions used. This assumption was substantiated by the small coupling constant (Jvic = 2.0 Hz) that was consistently observed for all telomers. Rigorous proof of the trans stereochemistry comes from the chemical transformations of the telomers. Thus, compounds of the general formula 14 contain protected a-hydroxyaldehyde function, and in principle they should be readily transform-... 

An olefin of defined stereochemistry about the double bond can readily be converted into a threo or erythro diol by direct cij-hydroxylation or by epoxidation followed by hydrolytic opening of the epoxide obtained ( franj-hydroxylation ). cjj-Hydroxylation of a cis olefin leads to an erythro diol and formation of an epoxide and its hydrolysis gives a threo stereoisomer. Conceivably, from a trans olefin both stereoisomeric diols may be obtained by cis- or frans -hydroxylation applied in the reversed way. 

If you worked Problem 2.29 (p. 85), you saw that there are two isomers of ra r-l,2-dimethylcyclopropane. We will see in this chapter why two trans-1,2-dimethylcyclopropanes exist and continue with a detailed discussion of stereochemistry, the stmctural and chemical consequences of the arrangement of atoms in space. We have already seen several examples of stereoisomeric molecules, compounds that differ only in the spatial arrangement of their constituent parts. The compounds cis-and ra r-l,2-dimethylcyclopropane are stereoisomers (as are all cis/trans pairs). Substituents on both ring compounds and alkenes can be attached in two ways cis and trans (Fig. 4.1). We will soon see that the two rflw -l,2-dimethylcyclopropanes are stereoisomers of a different kind. 

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