Stereoselectivity magnesium chelate

Lithium and magnesium chelates have no effect on the stereoselection of this reduction. Triisobutylborane is somewhat more effective than n-butylboranc no reduction occurs if tri-.sec-butylborane is used. 

All in all we successfully generated the 11 stereocenters of 9(S)- dihydroery-thronolide A in a 20 step sequence. The stereoselective chain extension reactions were not the ones which caused difficulties. Difficulties were encountered at the refunctionalization steps We had to try very hard to realize the reductive opening of the C6-C7-epoxide, a transformation in which a whole set of standard reagents failed, both at the stage of 29, 30 or its 0-protected derivatives. Finally, internal activation via a magnesium chelate allowed for the long sought after transformation of 30 into 31. 

On the contrary, in the latter case, a total loss of stereoselectivity occurs68. TV-Bis-benzyl-a-amino aldehydes 1 (R = R3 = Bn) under the assistance of boron trifluoride, zinc bromide or tin(lV) chloride lead to the nonchclation-controlled adducts preferentially, whereas titanium(IV) chloride or magnesium bromide result in chelation control70. In some cases, the O-trimcthylsilyl cyanohydrins arc the primary products, but the workup procedure usually provides the desily-lated products. 

However, the formation of a conformationaly rigid chelate with a fixed geometry is generally admitted in the transmetallation of organolithiums with magnesium halides. That explains the stability of the enolate and the stereoselectivity of its reactions. 

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-... 

The last steps of the synthesis, en route to synthon 157, consisted of chain elongation at C6 using a suitable carbanion. An acetylenic carbanion, representing C2-C3 of 151, was chosen because of a known propensity to add stereoselectively but also because they are good precursors of ketones. A brief study showed that the chelation controlled addition, that is, the use of magnesium derivatives, led to the required stereochemistry at C6. Other examples of such chelation controlled addition will be given in the following sections. 

The chelate rule will only be applicable if addition via the chelate is faster than addition by the acyclic mechanism i.e, kc > ka in Scheme 4.2). Because the chelate is rigid, it is often considerably more stereoselective as well. However, the relative rate issue is independent of the stereoselectivities of the two processes. For example, chelation can be used to control regiochemistry selective reduction of a diester is achieved by preferential chelation to a 5-membered ring over a 6-membered ring by magnesium bromide (Scheme 4.3, [40]). 

The enhanced syn stereoselectivity again can be explained by chelation of magnesium to the aldehyde, leading to an antiperiplanar transition state 499 in which steric interactions are minimal. 

Aldehyde 50 is an excellent chiral intermediate in reactions with organometallics. Addition at —78 °C of vinylmagnesium bromide to 50, that has been precomplexed with magnesium bromide etherate, affords the chelation-controlled product 51 with remarkably high diaster-eofacial selectivity (155 1). It is imperative that methylene chloride be used as the solvent in order to achieve this level of selectivity. In fact, if commercial vinylmagnesium bromide in THF is to be employed, the THF must be removed and replaced with methylene chloride [13] or else selectivity drops to 40 1. An analogous reaction of 50 with allyl tri- -butylstannane at — 23 °C furnishes chelation-controlled product 52 with 49 1 stereoselectivity. 

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