Chemistry Reference
In-Depth Information
i-Pr
i-Pr
i-Pr
i-Pr
R
R
Br
H
N
Mo
N
R
R
Me
Me
N
Mo
Ph
OH
R
Ph
Me
N
+
Me
O
R
OTBS
Br
C
6
H
6
, 22°C, 1 h
Br
R
N
TBSO
R
Br
5a
R = H; >98% conv; dr = >20:1
5b
R = Me; 95% conv; dr = 7:1
1 mol %
i-Pr
i-Pr
N
Mo
Me
N
Ph
Me
O
Cl
Cl
N
N
6b
(5:1 dr, in sit
u
)
TBSO
H
H
>98% conv, 84% yield
96% ee
C
6
H
6
, 22
°
C, 1 h
5 mol % PtO
2
H
2
, EtOH,
22 °C, 1 h
N
(+)-Quebrachamine
Et
H
97% yield
Scheme 8E.8.
Stereoselective synthesis of stereogenic-at-Mo complexes and application to enanti-
oselective total synthesis of quebrachamine.
Based partly on recent theoretical studies by Eisenstein and coworkers regarding
more reactive high oxidation state olefi n metathesis catalysts [33], Mo-based complexes
5
-
6
were designed and prepared. These chiral complexes feature one relatively electron-
donating ligand (pyrrolide) and one relatively electron-withdrawing ligand (aryloxide);
consequently, Mo is a stereogenic center and, as with stereogenic-at-metal Ru-based
catalysts (see Scheme 8E.4), undergoes inversion at the metal with each olefi n metathesis
transformation. The stereogenic-at-Mo complexes can be generated
in situ
through an
unprecedented stereoselective protonation of a metal-N bond (complexes are formed in
up to
20:1 dr), constituting the fi rst stereoselective synthesis of a stereogenic-at-metal
complex, bearing only monodentate ligands. Complexes containing a 2,5-dimethylpyr-
rolide ligand (e.g.,
5b
and
6b
) are exceptionally reactive and promote enantioselective
RCM with outstanding selectivity. Such developments have allowed the completion of
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