Polyoxygenated ketopinic-acid-derived γ-amino alcohols in the enantioselective diethylzinc addition to benzaldehyde

Different influence of polyoxygenation on the catalytic activity of amido- versus amino-isoborneols

“…In contrast, the related amino alcohols 4a-c did show different behavior, and even a reversal in the enantioselectivity, depending on the polyoxygenation. 19 This different behavior of amino and amido isoborneols can be explained on the basis of the empirical catalyst models used previously by us 10 and 11 ( Figure 5), hence corroborating our hypothesis. 20 Thus, for amino isoborneols, the groups attached to the nitrogen that coordinates the catalytic zinc are near the active site of the catalyst 10.…”

“…The catalytic activity of ligands 4a-c has been included for comparison. 19 The data from Table 1 show that there is no change in the catalytic activity of amido isoborneols 7a-c as a consequence of the different number of oxygen atoms present in the structure of the ligand. In contrast, the related amino alcohols 4a-c did show different behavior, and even a reversal in the enantioselectivity, depending on the polyoxygenation.…”

“…The first step was the amidation of the acid with the corresponding oxygenated amine, promoted by EDC/DMAP, which afforded the intermediate keto amides 9 in good yields. 19,22 Next, a chemo-and stereoselective reduction of the ketone group with NaBH4 gave the exo-hydroxy derivative 7 (isoborneol derivative) in good yields and very high stereoselectivity 23 (Scheme 2). Scheme 2.…”

“…In this sense, we have reported a study on the effect of polyoxygenation on the catalytic activity of a series of amino isoborneols 4a-c (Figure 2). 19 We found a switch in the enantioselection of the ligands based on the polyoxygenation. We explained this switch by competition by a new transition state 6 (Figure 3), where the two additional oxygen atoms in the ligand act as a pincer, directing the diethylzinc molecule to the si face of benzaldehyde.…”

“…20,21 The advantage of the ligands having an amido group is that they are easily prepared and much more inert and stable than their analogous amines. In principle, the activity of these ligands could also be modulated by polyoxygenation of their amide moieties, as was the case for related amino isoborneols, 19 however the effect of polyoxygenation in amido isoborneols has not been studied yet.…”