Stereogenic double bond

If a stereogenic double bond is established by this Elcb elimination, one usually observes a trans- or an / -sclcctivity. This experimental finding could have two origins (1) product development control (Section 4.1.3), if the stereoselectivity occurs under kinetic control, or (2) thermodynamic control. Thermodynamic control comes into play if the cis, trans- or E,Z-isomeric condensation products can be interconverted via a reversible 1,4-addition of NaOH or KOH. In the trans- or isomer of an ce,/l-un saturated carbonyl compound the formyl or acyl group may lie unimpeded in the plane of the C=C double bond. This geometry allows one to take full advantage of the resonance stabilization C=C—0=0 <-> C—C=C—0 . ... 

Ireland-Claisen rearrangements frequently are used for the synthesis of alkenes. This works particularly well if the allyl ester is derived from a secondary allyl alcohol. In this case a stereogenic double bond is formed in the rearrangement. The examples in Figure 14.48 show that the alkene is mostly trans-configured if this C=C bond is 1,2-disubstituted and almost completely is-configured if it is trisubstituted. 

In all these reactions, any existing configuration of any stereogenic double bond—whether it be in the alkenyl bromide or iodide or in the alkenyl Grignard compound- is completely retained. The reactions in Figure 16.10 provide good examples. 

In the course of a sulfonium ylide rearrangement a maximum munber of three stereogenic units can be generated (Scheme 87). The resulting homoal-lylic sulfide 354 contains up to two stereogenic centers and one stereogenic double bond. Based on the work of Houk [204] with R = H, the following simphfied transition-state models can be discussed (Scheme 88). 

In this chapter we describe the unified generation of stereoisomers including conform-ers of a molecular structure [102,103,105]. This method has the potential to generate stereoisomers that cannot be described in terms of stereocenters, stereogenic double bonds or single bond rotations. Fundamentals such as the concept of a (partial) orientation function are discussed, and mathematical tools such as Radon partitions and binary Grassmann-Plucker relations are used to construct tests for abstract orientation functions. Some simple examples are treated in detail. 

Fig. 4.1. Three chiral compounds whose stereoisomerism cannot be described in terms of stereocenters, stereogenic double bonds, or rotatable single bonds.

Both kinds of programs will miss any stereoisomers whose existence cannot formally be traced to the presence of stereocenters or stereogenic double bonds or to rotation about rotatable single bonds. Thus, the chiraUty and therefore the existence of enantiomers for e.g. [2,2]paracyclophanecarboxylic acid A, 1,12-dimethyl-benzo[c]phenanthrene B, and ( [-cyclooctene C (Figure 4.1), as well as for chiral fullerenes such as C76 cannot be detected by any of the current programs due to then-conceptual limitations. 

Stereogenic double bonds are not expected to cause major problems to this approach, since a double bond was shown already by Nourse to be treatable as a special kind of stereocenter. The suggested selection of quadruples of types i) and ii) is not able to distinguish between 60° and 90° torsion angles. An open question is whether these are distinguished by selecting another few quadruples. 

The BF3 Et20-promoted addition of racemic y-aUcoxyallylstannane 162 to a norephedrine-derived 2-methoxy-oxazolidine 163 afforded only two diastereomeric adducts 164, out of the eight possible (two stereogenic centres plus a stereogenic double bonds are generated in the condensation) in a 95 5 ratio [96]. The reaction showed a strong kinetic preference for consumption of the (S)-y-stannane 162. 

There are three stereogenic double bonds in discodermolide, labeled with arrows,... 

The bond 2-3 of 10 is a stereogenic double bond. The implicit hydrogen is again assumed to have the highest number. Atoms 1, 3, and the implicit hydrogen are drawn counterclockwise, while 2,4, and 7 are clockwise. Therefore the bond 2-3 is assigned the parity (-2). 

Unsaturated -lactone 34 adopts a well-defined conformation and provides a suitable platform for the introduction of the stereogenic center at C-24 (monensin numbering). Catalytic hydrogenation of the carbon-carbon double bond in 34 takes place preferentially from the less hindered side of the molecule and provides an 8 1 mixture of stereoisomers in favor of 35 (100% yield). Cleavage of -lactone 35 with concentrated hydriodic acid at 130°C, followed by treatment of the resultant iodide 36 with triphenylphosphine, completes the synthesis of intermediate 19. 

In contrast to the open-chain and dipolar models, which are based on conformations of the carbonyl compound not representing energy minima, Karabatsos proposed a different model assuming an early, reactant-like transition state in which the most stable conformation of the free carbonyl compound is preserved1314. Thus, the C-M bond eclipses the carbonyl double bond and, in order to minimize the energy of the transition state, the nucleophile approaches close to the small substituent on the stereogenic center (Figure 5). 

For a successful application in synthesis, several problems have to be solved regioselectivity, whether the C-C bond is formed with the 1- or 3-position in an unsymmetrical ambident anion, EjZ selectivity in the formation of the double bond, and simple diastereoselectivity, since two new stereogenic centers are created from prostereogenic compounds. Further, different types of induced stereoselectivity or enantioselectivity may be required. Allylmetals with a wide choice of substituents are accessible by various methods (Sections D. 1.3.3.3.1.-10.). 

Active Substrate. If a new stereogenic center is ereated in a molecule that is already optically active, the two diastereomers are not (except fortuitously) formed in equal amounts. The reason is that the direction of attack by the reagent is determined by the groups already there. For certain additions to the carbon-oxygen double bond of ketones containing an asymmetric a carbon. Cram s rule predicts which diastereomer will predominate (diastereo-selecti vity). ... 

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