Cyclic compounds stereogenic centers

The stereoselectivity of an addition reaction is considerably lower when the reactions are conducted in polar solvents, complexing additives such as /V./V,A. A, -tetramethylethylenedi-arnine arc used, or when the stereogenic center carries a methoxy group instead of a hydroxy group. This behavior is explained as competition between the cyclic model and a dipolar model, proposed for carbonyl compounds bearing a polar substituent such as chlorine with a highly... 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

Cyclic diastereomers are compounds in which the stereogenic centers are within a molecular fragment which is cyclic. 

On the other hand, acyclic diastereomers are not necessarily compounds without any cyclic structural element, but the fragment connecting the stereogenic centers is acyclic. For example, a bicyclo[2.2.1]heptane derivative with a chiral side-chain attached to a nonbridgehead carbon belongs to this second category of acyclic diastereomers. 

Thus, a popular and reliable method of determining relative configuration of open-chain compounds is to convert them into more or less rigid cyclic derivatives by chemical reactions that leave the stereogenic centers unchanged (see Section 4.1.3.1.). Unfortunately, such reactions are not always readily available. 

The chemical transformation must not affect the stereogenic centers. Suitable acyclic candidates are compounds with easily convertible functional groups, such as diols, diamines, amino alcohols, dicarboxylic acids and so on. A number of procedures known before 1973 have been compiled, including conversion of diols and amino alcohols into sulfites or 1,3-dioxolanes by thionyl chloride, or acetalization with ketones31,1"319, as well as the conversions of dinitriles into imides320, dicarboxylic acids into cyclic anhydrides or imides321, and hydroxy acids into oxazolidones 322. 

Cases where the stereogenic centers are further removed from the prostereogenic one — e.g. in compounds of type Ph—CHX—CH2—CMe2—CH2—CHX—Ph — have also been investigated in both acyclic 59) and cyclic 60) systems. 

The 191 problems in this book cover most of the area of stereochemistry, including nomenclature, stereogenic elements (centers, axes, planes) and their descriptors, symmetry, inorganic stereochemistry, determination of enantiomer excess, conformation of acyclic and cyclic compounds, and more. The answers, in addition to providing solutions to the problems, frequently include additional explanations of the underlying principles. The problems are ordered more or less in order of increasing difficulty. (I had a hard time with some of the problems toward the end myself )... 

Enol Amination. The Cu[(S,5)-t-Bu-box] (OTf)2 complex was found to be optimal for promoting the enantioselective conjugated addition of enolsilanes to azodicarboxylate derivatives (eq 13). This methodology provides an enantioselective catalytic route to differentially protected ot-hydrazino carbonyl compounds. Isomerically pure enolsilanes of aryl ketones, acylpyrroles, and thioesters add to the azo-imide in greater than 95% ee. The use of an alcohol additive was critical to achieve catalyst turnover. Amination of cyclic enolsilanes was also possible. For example, the enolsilane of 2-methylindanone provides the adduct containing a tetrasubstituted stereogenic center in 96% ee and high yield. Acyclic (Z)-enolsilanes react in the presence of a protic additive with enantioselection up to 99%. ... 

Stereogenic centers 53 Stereogenic centers in cyclic compounds... 

The resolution by enantioselective hydrolysis of cyclic carbonates and 2-oxazolidinones is particularly interesting with respect to the latter class of compounds, in which the ester group is attached to a side chain while the stereogenic center is in the ring. 

Remarkably, the reaction also tolerated the use of differently substituted a-alkyl-p-ketoesters as Michael donors, leading to the formation of compounds containing two contiguous stereogenic centers, one of them a quaternary one, in good diastereo- and enantioselectivities (Scheme 4.6). Masked cyclic 1,3-diketones such as 2-hydroxy-1,4-naphthoquinols have also been successfully applied in this context also showing the extraordinary performance of catalyst 68a in terms of both yields and enantioselectivities. There is also one example of a vinylogous Michael reaction between a,a-disubstituted dicyanoacrylates and nitroalkenes for which Takemoto s catalyst has also been identified as the most efficient promoter of the reaction. Moreover a solid-supported version of this catalyst has also been developed by Takemoto himself and tested in the reaction of diethylmalonate with nitrostyrene with success. ... 

For stereogenic centers in cyclic compounds, the same rule for assigning priorities is followed. For example, in 1,1,3-trimethylcyclohexane, the four groups attached to carbon-3 in order of priority are —CH2C(CH3)2CH2 > —CH2CH2 > —CH3 > —H. 

When a molecule has two or more stereogenic (chiral) centers, there are a maximum of 2" stereoisomers, where n = the number of chiral centers. When a molecule has two or more chiral centers, diastereomers are possible. Diastereomer is the term for two or more stereoisomers that are not superimposable and not mirror images. A diastereomer that has symmetry such that its mirror image is superimposable is called a meso compound. If there is no symmetry, cyclic molecules can have enantiomers and diastereomers. If there is symmetry in one diastereomer, cyclic compounds can have meso compounds 23, 24, 25, 26, 27, 28, 29, 30, 48, 49, 59, 60, 62,63,67,68,69, 70, 71, 75, 78, 79. 

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