Improved Methodology for the Preparation of Chiral Amines

Substrate Categories.
I found that the biggest jump for de is associated with straight-chain 2-alkanones (e.g.
2-octanone) and γ-branched 2-alkanones (e.g. benzylacetone). These groups of
substrates are good substrates for this methodology in terms of high
diastereoselectivity. α- and β-branched 2-alkanones did not show any significant
increase in the de. This effect can be rationalized through understanding the nature of
R group attached to of the two Newman projections in gauche and anti conformations
illustrated in (scheme 7.2).
When α- and β-branched 2-alkanones (when R α or R β = alkyl respectively) are used
with Yb(OAc) 3 , no improvement of diastereoselectivity was noticed as Illustrated
from the scheme. This finding implies that the energy difference between the gauche
and the anti conformations is not significant. This means that steric crowding of the
“α-methylbenzyl” substituent on the nitrogen atom and the “R” substituent of the
former carbonyl carbon in the gauche conformation vs the steric crowding
experienced when the “ytterbium” substituent of the nitrogen atom is gauche the “R”
substituent of the former carbonyl carbon of the anti conformation has almost the
same energy. On the other hand, examination of the energy difference of the gauche
and anti conformations of γ-branched 2-alkanones and straight chain 2- alkanones
shows that the anti congregation is lower in energy compared to the gauche
conformation. The effect is more pronounced in straight chain 2-alkanones compared
to γ-branched 2-alkanones. This difference in energy can be rationalized by noting
that the “α-methylbenzyl” substituent of nitrogen is sterically very crowded α to the
nitrogen, while the ytterbium-nitrogen bond will be expected to be longer than the
benzylic carbon-nitrogen bond of the “α-methylbenzyl” substituent and thereby
reduce the immediate steric volume next to nitrogen.
The conclusion is that regardless of the steric bulk of the “R” substituent, there is
always a high degree of steric crowding when the “α-methylbenzyl” substituent on
nitrogen is gauche to it (Figure 2, gauche-6). To account for the observed
enhancement in de, “R” substituents (Scheme 3) having only γ-branching (Figure 3,
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