Stereogenic centres

Cyclobutene-containing dienylcarbene complexes react with alkynes to form cyclooctatrienone derivatives [127]. The reaction proceeds in a regioselective fashion leading to a mixture of diastereoisomers due to the newly created stereogenic centre (Scheme 79). This process can be viewed as a variation of the... 

Hydro carbonylation of olefins, hydroformylation, hydroesterification and hy-droxycarbonylation are reactions which appear to be of particular interest. Indeed, they allow the simultaneous creation of a new C - C bond as well as the introduction of a functional group (aldehyde, ester and acids). One or two new stereogenic centres can thus be formed at the same time (Scheme 26). Despite the difficulty of using high carbon monoxide pressure, the aheady existing industrial processes prove that such reactions can be performed on a very large scale [107]. 

Enzyme-mediated syntheses of chiral non-racemic hetero-organic compounds, with a stereogenic centre located either on a heteroatom or on a carbon atom in a side chain, are comprehensively presented. Particular attention is paid to the use of common hydrolytic and reducing enzymes. On the basis of the results presented, some conclusions are drawn and proposals presented, which concern possible future direchons in the applications of enzymes to the synthesis and transformations of chiral hetero-organic derivatives. 

Searching for a method of synthesis of enantiopure lamivudine 1, the compound having a monothioacetal stereogenic centre, Rayner et al. investigated a lipase-catalysed hydrolysis of various racemic a-acetoxysulfides 2. They found out that the reaction was both chemoselective (only the acetate group was hydrolysed with no detectable hydrolysis of the other ester moieties) and stereoselective. As a result of the kinetic resolution, enantiomerically enriched unreacted starting compounds were obtained. However, the hydrolysis products 3 were lost due to decomposition." In this way, the product yields could not exceed 50% (Equation 1). The product 2 (R = CH2CH(OEt)2) was finally transformed into lamivudine 1 and its 4-epimer. ... 

Kielbasirtski, P. Mikolajczyk, M. In Hydrolytic Enzymes in the Synthesis of Non-racemic Heteroorganic Compounds with a Stereogenic Centre on the Heteroatom, Enzymes in Action Green Solutions for Chemical Problems Zwanenburg, B. Mikolajczyk, M. Kielbasifiski, P. (Eds) Kluwer Dordrecht 2000, pp. 161-191. 

Gourtieu, J. Deuterium NMR stereochemical analysis of threo-erythro isomers bearing remote stereogenic centres in racemic and non-racemic liquid crystalline solvents. Tetrahedron Asymmetry 2000, 11,1911-1918. 

Scheme 1.69 Test reaction with S/N-ferrocenyloxazoline ligands bearing two stereogenic centres.

In another context, Davies et al. have developed the Rh2(-S -DOSP)4-catalysed decomposition of vinyldiazocarbonyl derivatives in the presence of vinyl ethers.The corresponding chiral cyclopentenecarboxylates were formed in high enantioselectivities of up to 99% ee with the full control of the relative stereochemistry at up to three contiguous stereogenic centres, as depicted in Scheme 10.9. 

This point of view finds its justification in the following observations. Compounds 8 (pyrocalciferol) and 9 (isopyrocalciferol), having opposite absolute configurations of the stereogenic centres near the dienes, show lA —> 1B Cotton effects at about 275 nm of the same sign and intensity. The reason for this is that only the twist of the chromophore determines the optical activity in fact the diene moieties are distorted in the same sense in 8 and 9, as found by X-ray diffraction16. 

Secondary allylic alcohols also undergo asymmetric epoxidation in many cases, when the alcohol unit is attached to a stereogenic centre, kinetic resolution of the enantiomers takes place. This is particularly apparent for compounds of type (25), where the two enantiomers are epoxidized at rates which are different by two orders of magnitude1861. 

A more recent synthesis of 197 [365] is shown in Fig. 9. Enders introduced the stereogenic centre of (S)-lactic acid into the crucial position 10 in 197. The vinylsulfone B, readily available from lactic acid, was transformed into the planar chiral phenylsulfonyl-substituted (q3-allyl)tetracarbonyliron(+l) tetra-fluoroborate C showing (IR,2S,3 )-configuration. Addition of allyltrimethyl silane yielded the vinyl sulfone D which was hydrogenated to E. Alkylation with the dioxolane-derivative of l-bromoheptan-6-one (readily available from 6-bro-mohexanoic acid) afforded F. Finally, reductive removal of the sulfonyl group and deprotection of the carbonyl group furnished 197. A similar approach was used for the synthesis of 198 [366]. 

When we look more closely at the intermediate polymer chain we see an alternative explanation emerging. After the first insertion has taken place a stereogenic centre has been obtained at carbon 2, see Figure 10.4. Coordination with the next propene may take place preferentially either with the re-face or the si-face, with the methyl group pointing up or down, as displayed in Figure 10.4. 

Summarising, in the chain-end control mechanism the last monomer inserted determines how the next molecule of 1-alkene will insert. Several Italian schools [7] have supported the latter mechanism. What do we know so far Firstly, there are catalysts not containing a stereogenic centre that do give stereoregular polymers. Thus, this must be chain-end controlled. Secondly, whatever site-control we try to induce, the chain that we are making will always contain, by definition, an asymmetric centre. As we have mentioned above, the nature of the solid catalysts has an enormous influence on the product, and this underpins the Cossee site-control mechanism. Thus both are operative and both are important. Occasionally, chain-end control alone suffices to ensure enantiospecifity. 

As we have seen above polymerisation of all prochiral alkenes produces a new stereogenic centre for each monomer inserted. In a site-controlled... 

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