Improved Methodology for the Preparation of Chiral Amines

anti-6) would be expected to have medium steric crowding with a gauche ytterbium
atom, while non-branched “R” substituents would have low steric crowding in
relation to a gauche positioned ytterbium atom. These considerations would thus favor
cis-imine to trans-imine isomerization for straight-chain 2-alkanones and γ-branched
2-alkanones, but exclude isomerization for α- and β-branched 2-alkanone substrates.
R γ
R α
R α
R
R β
Ph
N
O
CH 3
Yb
O
~=
R
R γ
R β
Yb
O
N
O
CH 3
Ph
gauche-6
R α or R β = alkyl
anti-6
R γ
R γ
R
Ph
N
O
CH 3
Yb
O
>
R
Yb
O
N
O
CH 3
Ph
gauche-6
R α and R β = H
anti-6
R
Ph
N
O
CH 3
Yb
O
>>
R
Yb
O
N
O
CH 3
Ph
gauche-6
R α , R β , and R γ = H
anti-6
Scheme 7.2. Newman Projections Showing Interactions of Ytterbium Acetate with R
Group.
Because no other lanthanide acetates were identified as capable of providing
enhanced de, ytterbium would appear to have unique coordination sphere attributes
(Lewis acidity and high coordination number) allowing the proposed in situ
isomerization to occur. Furthermore a unique and critical role is indicated for the
acetate ligand. The mechanism presented here is more likely than those in which
simple ligation of Yb(OAc) 3 to the in situ formed trans- and cis-imine mixture allows
constructive influence of the rotamer environment, about the benzylic carbon-nitrogen
bond of the ketimine, and thereby improved facial selectivity during reduction. This is
135