Double-stereodifferentiating experiments

Scheme 15. Double-stereodifferentiating experiments aimed at elucidating solution geometry of 55c Cu(II) dienophile complexes. [Adapted from (200).].

Double stereodifferentiating experiments [89] using chiral dienophiles have effectively ruled out the intervention of a tetrahedral copper center or a reactive s-trans conformer (Scheme 29) [82]. It is noteworthy that in the mismatched... 

However, one should not always expect to see additivity in such double stereodifferentiation experiments, as is illustrated by the following logic. For equation (129), AG° = +1.8 kcal mol" (1 cal = 4.18 J) that is, an axial methyl group disfavors the conformation on the right by 1.8 kcal mol". In equation (130), the effects of two axial methyl groups are additive, and AG° = 3.6 kcal mol. However, in equation (131), the effects of the two axial methyl groups are not additive, and AG° 3.6 kcal mol". Thus, we should expect that there will be cases in which the ideas of consonant and dissonant double stereodifferentiation will break down. ... 

Double stereodifferentiation experiments with matched chiral aldehyde 199 provided anti aldol 200 as a single diastereomer, as shown in Scheme 2.18 [67]. 

Thought Experiments II and III on the Hydroboration of Chiral Alkenes with Chiral Boranes Reagent Control of Diastereoselec-tivity, Matched/Mismatched Pairs, Double Stereodifferentiation... 

Thought experiment III in Figure 3.27 provides an example of how such a double stereodifferentiation can be used to increase stereoselectivity. The two competing hy-... 

The aldol condensation, one of the oldest organic reactions, is emerging as a powerful method for control of relative and absolute stereochemistry in the synthesis of conformationally flexible compounds. Some of the research which has been carried out at Berkeley over the past five years is reviewed in this article. Points discussed are the factors that control simple erythro, threo diastereoselection, the use of double stereodifferentiation to influence the "Cram s rule" preference shown by chiral aldehydes, and some recent experiments that shed light on the role that the solvent and other nucleophilic ligands play in determining the stereochemistry of the reaction. 

Next, the double-stereodifferentiating [27] aldol process with a-chiral aldehydes was examined, seperate experiments using both enantiomeric forms of phenyl propionaldehyde were undertaken. Use of (S)-phenylpropionalde-hyde 28 gave two diastereomers 29 and 30 in a ratio of 2.5 1 and 68% yield. The major one is still the anti-Cram/Felkin compound 29, which is quite unusual because 28 usually provides high selectivity in favor of the Cram/ Felkin adduct 30 [28]. 

In a further series of experiments Danishefsky employed chiral ketones of type 59. Both enantiomers were available with high optical purity and could be involved in investigations in the double stereodifferentiating aldol reaction. However, the lithium anion of 59 (R = TBS) could not be effected in useful yield due to the sensitivity of the j5-silyloxy system to elimination. The less basic titanium enolate of 59 gave mixtures of diastereomers in moderate yields. The stereochemical outcome of these reactions showed that the configuration at C3 rather than C8 had a larger effect on the newly... 

These results are explained in terms of coordination of the nucleophilic hydroxy-(methoxy-, silyloxy-, amino-) functionality of the stereogenic center with the incoming electrophilic singlet oxygen (Scheme 24, right side, transition states C). Stereodifferentiation results from the preferred conformation of the ally lie alcohol for oxygen transfer, which is mainly determined by 1,3-allylic strain (threo-C favored over erythro-C). The experiments also showed that the optimal dihedral angle of the allylic alcohol (C=C—C—O) in the transition state lies between 90° and 130° and the newly formed double bond in the... 

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