4 research outputs found
Enantioselective Cyclopropanation of Indoles: Construction of All-Carbon Quaternary Stereocenters
The first enantioselective copper-catalyzed cyclopropanation of <i>N</i>-acyl indoles is described. Using carbohydrate-based bis(oxazoline) ligands (<i>gluco</i>Box), the products were obtained in up to 72% ee. Cyclopropanation of <i>N</i>-Boc 3-methyl indole yielded a product with an all-carbon quaternary stereocenter, which is a valuable building block for the synthesis of indole alkaloids: Deprotection and rearrangement gave a tricyclic hemiaminal ester in 96% ee, which was subsequently employed as a key intermediate for the synthesis of (−)-desoxyeseroline
Efficient Pseudo-enantiomeric Carbohydrate Olefin Ligands
Highly efficient pseudo-enantiomeric olefin ligands were designed from d-glucose and d-galactose. These ligands yield consistently excellent levels of enantioselectivity in Rh(I)-catalyzed 1,4-additions of aryl- and alkenylboronic acids to achiral enones and high diastereoselectivity with chiral substrates. Contrary to established olefin ligands, they are obtained enantiomerically pure via short syntheses without racemic resolution steps, making them a valuable addition to the arsenal of chiral ligands with olefinic donor sites
Heteroarylboronates in Rhodium-Catalyzed 1,4-Addition to Enones
RhodiumÂ(I)-catalyzed
1,4-addition of aryl and alkenylboronic acids
to α,β-unsaturated carbonyl compounds is well established,
but the transfer of heteroaryl residues in this reaction remains underdeveloped.
We have studied heteroaryl MIDA and pinacol boronates as alternatives
to the labile boronic acid counterparts. Under racemic conditions,
12 adducts with heteroaryl residues, among them unsubstituted 3- and
4-pyridinyl, 2-furanyl, thienyl, and pyrrolyl groups, were obtained
in moderate to excellent yields. The enantioselective version of the
reaction proved highly sensitive to the electronic character of the
heteroaryl substituents, with boronates carrying electron-rich residues
giving modest to high yields but consistently high enantiomeric excesses
Cycloalkene Carbonitriles in Rhodium-Catalyzed 1,4-Addition and Formal Synthesis of Vabicaserin
Cycloalkenes
with exocyclic acceptor substituents still remain
challenging substrates for enantioselective rhodium-catalyzed 1,4-addition.
Cycloalkene carbonitriles and carboxylates have been investigated,
and a highly diastereo- and enantioselective protocol for 1,4-addition
to cyclopentene and cycloheptene carbonitrile has been developed.
This new asymmetric transformation was subsequently applied in the
asymmetric formal synthesis of the drug candidate Vabicaserin