Roseblade SJ, Casas-Arcé E, Nettekoven U, Smilović IG, Zanotti-Gerosa A, Časar Z *
Johnson Matthey, Cambridge, UK; Solvias AG, Kaiseraugst, Switzerland; Lek Pharmaceuticals,
Mengeš, Solvenia; Sandoz GmbH, Kundl, Austria; University of Ljubljana, Solvenia
A Practical Synthetic Approach to Chiral (α-Chloroalkyl)boronic Esters via Iridium-Catalyzed
Chemoselective Hydrogenation of Chloro-Substituted Alkenyl Boronates.
Synthesis 2013;
45: 2824-2831
Key words
iridium - hydrogenation - alkenyl boronates
Significance
Enantioenriched (α-chloroalkyl)boronic esters represent an important class of building
blocks frequently used in organic synthesis. These chiral halogenated compounds are
most commonly synthesized via Matteson-type rearrangements which use stoichiometric
lithiated reagents, leading to stoichiometric waste streams. Transition-metal-catalyzed
asymmetric hydrogenation has become the premier method for setting diversely substituted
stereocenters with high enantiomeric excess under more environmentally friendly conditions.
The authors report the synthesis of enantioenriched (α-chloroalkyl)boronic esters
via the iridium-catalyzed asymmetric hydrogenation of chloro-substituted alkenyl boronates.
Comment
The authors present a protocol for the enantioselective iridium-catalyzed hydrogenation
of chloro-substituted alkenyl boronates using a ferrocenyl phosphinoimidazoline ligand.
Good to excellent yields and enantioselectivities were obtained for both alkyl- and
aryl-bearing substrates. Substrate-to-catalyst ratios (S/C) of up to 25 and hydrogen
pressures as low as 5 bar are reported. This catalytic system benefits from a low
amount of dechlorinated products resulting from over-reduction.
