Diastereoselectivity diastereotopic group selectivity

An example of a condensation reaction with diastereotopic group selectivity (see appendix) is the lactonization of either of the two racemic, C2-symmetrical 5-hydroxy-2,4,6,8-tetramethylnonanedioic acids. This reaction desymmetrizes a compound with two pairs of equivalent stereocenters (C-5 is achiral ) into a product with five different stereocenters. The trilithium salt is generated by reduction of the 2,4,6,8-tetramethyl-5-oxononanedioic acid with lithium in ammonia and then either acidified to pH 3 followed by rapid extraction of the lactones formed (kinetic control) or equilibrated at pH w 1 to the lactone mixture (thermodynamic control). Depending on the steric interactions in the chair-like transition states and in the half-chair lactone products, either kinetic or thermodynamic control leads with high diastereoselectivity to the lactone with trans-configuration at C-5 and C-6 of the tetra-hydro-2/f-pyran-2-one ring (T. R. Hoye, 1984). 

Group-selective hydroalumination in which aluminum hydrides discriminate between diastereotopic alkynes provides access to a class of stereo-defined tertiary alcohols with potential ulilily in natural product synthesis [175]. Among the hydride reagents tested, BuLi-DIBAL or HSul.i-DIBAL enabled superior discrimination to give sp -sp -sp-attached alcohol 145 with extremely high diastereoselectivity (>99% de) (Scheme 6.136). 

In the discussion of the stereochemistry of aldol and Mukaiyama reactions, the most important factors in determining the syn or anti diastereoselectivity were identified as the nature of the TS (cyclic, open, or chelated) and the configuration (E or Z) of the enolate. If either the aldehyde or enolate is chiral, an additional factor enters the picture. The aldehyde or enolate then has two nonidentical faces and the stereochemical outcome will depend on facial selectivity. In principle, this applies to any stereocenter in the molecule, but the strongest and most studied effects are those of a- and (3-substituents. If the aldehyde is chiral, particularly when the stereogenic center is adjacent to the carbonyl group, the competition between the two diastereotopic faces of the carbonyl group determines the stereochemical outcome of the reaction. 

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