Chelation control model

Chelation Control Model- "Anti-Cram" selectivity... 

N-Monoprotected aldehydes reacted according to the non-chelation-controlled model. The best diastereocontrol (syn/anti, 20.6 1) was achieved with allyltrimethylsilane in the presence of tin tetrachloride. A similar method was used in the synthesis of the aminoglycosidic fragment of calicheamycin yj [36]. 

However, a reversal of the diastereofacial selectivity may arise when the substrate has, in a or f) position of the side chain, a group prone to complexation with the Lewis acid. Then, the use of bidentate Lewis acids such as MgBr2, TiCU or ZnCL allows the reaction to proceed under a chelation control model, providing preferentially the syn adduct for a 1,4-chelation and the anti adduct for a 1,5-chelation. This was exploited in the stereoselective synthesis of both diastereomers, simply by changing the chelation conditions on the substrate18. An impressive amount of work was done with various a-alkoxy aldehydes19-23 as a route to carbohydrate chemistry. Similarly, a-amino aldehydes were used as substrates for /3-amino alcohol synthesis24,25. 

Variation of 2-alkyl substituent exerted an effect upon diastereoselectivity. The best diastereoselection was obtained when incorporating a 2-ethyl substituent for acyl dithiane oxides (Table 3.6). The diastereoselectivity and the sense of induced stereochemistry can be rationalized on the basis of a simple chelation control model. 

In the early stages of the project, we reasoned that the sulfoxide unit might be expected to influence the transition state geometry of the 2-acyl side chain, perhaps by chelation to a metal counterion, and hence control the stereochemistry of a wide range of functional group transformations. Indeed, a chelation control model of the reactivity of the 2-acyl dithiane 1-oxide systems has allowed us to rationalize, and predict, the stereochemical outcome of most of the reactions studied so far. These predictions have, in many cases, been confirmed by X-ray structure determination of the relative stereochemistries within product structures.1-4... 

As can be seen from Table 2, very high stereoselectivities could be observed for both syn and anti substrates, depending on the 2-alkyl substituent (R). In the absence of ZnCl2, a nonchelated chairlike transition state was anticipated, following the Solladie model, with intramolecular hydride transfer. This process was expected to lead to an opposite sense of selectivity to that observed for the chelation-controlled model (with DIBAL/ZnCl2). This reversal in stereoselectivity was indeed observed... 

Syn 2-formyl-2-methyl-l,3-dithiane 1-oxide undergoes efficient cycloaddition reaction with Danishefsky s diene with excellent levels of diastereoselectivity in the presence of magnesium bromide at -78 °C (Scheme 9, Table 10). Chelation control models which are similar to those described previously by us, and others,54 were proposed to rationalize the observed stereoselectivity. The proposed model 29 for the syn system is shown below the structure of the major product diastereoi-... 

Another class of chelation-controlled reactions involves Sml2, which has been used to mediate inter- and intramolecular ketone-olefin couplings [17], Matsuda and collaborators showed that coupling erpt/ira-) -hydroxyketone with acrylonitrile led exclusively to the anti diol under Sml2 reductive conditions [18]. Chelation control model J in Scheme 6 was proposed to account for the sense of diastereo-selectivity. In this model, chelation of the Smb to both the jff-hydroxy and the... 

Lewis acids that possess two empty sites of coordination are cqiaUe of imposing conformational constraints on a carbonyl ligand either by forming 2 1 complexes or via chelation when a second basic site is present in the ligand. Despite the popularity of the chelation-control model since its original proposal in 1952 by Cram and coworkers, rigorous and direct experimental evidence for chelation in a- and (3-alkoxycarbonyls was only obtained recendy from variable temperature H and C NMR. " ... 

Most attempts to construct diastereoselective variants of the Passerini reaction have met with a certain degree of failure. Undoubtedly, the numerous uncertainties of the reaction mechanism have contributed to these difficulties. The usual low levels of control for the Passerini reaction have also impeded efforts to establish empirical trends in the diastereofacial selectivity. This is exemplified in the construction of peptidomimetics, a class of molecules which has stimulated numerous applications of the Passerini reaction, where the diastereoselectivity is typically in the range of 1 1 to 4 1, A survey of results of the diastereofacial selectivity of carbonyl addition does not consistently follow a clear trend of either the Felkin-Anh or chelation-controlled models of carbonyl addition. ... 

The stereochemical outcome of these reactions has been rationalized by use of a chelation-controlled model. In this model, the titanium enolate... 

---