4th EucheMs chemistry congress

thursday, 30-Aug 2012
s779
chem. Listy 106, s587–s1425 (2012)
organic Chemistry, Polymers – i
Natural products, Drugs – iii
o - 4 8 7
CASe StudieS of ASyMMetriC hydroGenAtion
of ChALLenGinG PhArMACeutiCALLy
reLevAnt SuBStrAteS
v. JurCiK 1
1 Johnson Matthey Catalysts, Chiral Catalysts and
Technologies, Cambridge, United Kingdom
Two recent case studies of asymmetric hydrogenation of
unusual and challenging pharmaceutically relevant substrates will
be presented. Emphasis on challenges of industrially applicable
catalytic transformations will be given.
First case study will show efficient asymmetric
hydrogenation of (1-chlorovinyl) boronates. [1]
Broad range of substituted (1-chlorovinyl) boronates, with
different steric and electronic properties, can be successfully
hydrogenated in the presence of P^N-iridium catalysts without
significant cleavage of the C-Cl bond.
It will be shown how rational modification of the
structural properties of the P^N ligands can result in new
N-acyl-imidazoline ferrocenyl-based iridium catalysts with broad
substrate acceptance. With these catalysts, excellent conversions,
high chemoselectivities (with dechlorinated byproducts in the
range of 3–19%), and enantioselectivities of up to 94%ee can be
obtained. The utility of the hydrogenation method presented will
be demonstrated on preparation of a key precursor for the
construction of the anticancer drug bortezomib.
Second case study will deal with development of
asymmetric hydrogenation of a pyridyl benzo thiophene alkene. [2]
Studied transformation represents a key step in enantioselective
synthesis of NBI-75043, a selective and potent H1 antagonist for
the treatment of insomnia.
Reduction can be successfully accomplished using
[BoPhoz Rh] catalysts. By tailoring the steric properties of the
BoPhoz ligand, the ee of the product can be increased from just
12% to 90%. This research further expands the substrate scope
of the conventional class of functionalized alkenes amenable
to catalytic asymmetric hydrogenation.
references:
1. Angew. Chem. Int. Ed. 2012, 51, 1014–1018
2. Tet. Lett. 2012, 53, 1025–1028
Keywords: Asymmetric catalysis; Hydrogenation;
4 th EucheMs chemistry congress
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc