2880-06-0Relevant articles and documents
Chiral Ugi-type amines: Practical synthesis, ligand development, and asymmetric catalysis
Wang, Chun-Jiang,Dong, Wu-Wei,Li, Yi-Nan,Chang, Xin,Shen, Chong
, p. 12954 - 12959 (2020/11/17)
Ugi's amine has become one type of privileged chiral skeleton for chiral ligand design bearing central/planar chirality, and such ligands have exhibited tremendous success in various asymmetric catalysis. However, the current access to enantiopure Ugi's amine is quite tedious and relies heavily on optical resolution, which impedes its practical applications, to some extent. Herein, we present a facile asymmetric synthesis of enantioenriched Ugi-type amines bearing a long-carbon chain through Ir-catalyzed cascade allylation/2-aza-Cope rearrangement, followed by amino exchange and Pd/C-catalyzed one-pot hydrogenation/reductive amination. The protocol could be readily scaled up, and it has been conducted in 20-g-scale asymmetric synthesis of (S)-Ugi-type amine from commercially available reagents, in >99% ee and >70% overall yield in four steps with one short silica gel-plug purification. (S,Rp)-PPFA-type and (S,Rp)-Josiphos-type ligands, readily prepared from the achieved Ugi-type amine, exhibited higher or comparable asymmetric induction and catalytic efficacy in several Cu(I)-catalyzed asymmetric reactions, which indicated great potential of the applications of the readily accessible Ugi-type amines in ligand/catalyst design.
On the mechanism of Cu-catalyzed enantioselective extended conjugate additions: A structure-based approach
Hartog, Tim Den,Huang, Yange,Faans-Mastral, Martn,Meuwese, Anne,Rudolph, Alena,Prez, Manuel,Minnaard, Adriaan J.,Feringa, Ben L.
, p. 560 - 574 (2015/03/04)
The enantioselective 1,6-addition to unsaturated carbonyl compounds offers unique opportunities to study the range of selectivities one can obtain using Cu catalysis. Here, a substrate-reagent approach to obtain structural information on the mechanism of extended conjugate additions is reported. By studying the influence of several halides in the Grignard reagent and in the Cu source on the enantioselective 1,6-addition, it was shown that it is advantageous to use a combination of EtMgBr as Grignard reagent and CuI as Cu source. Furthermore, exploring substrates bearing several alkyl esters revealed that tBu-ester substrates enhance the enantiodiscrimination in the 1,6-addition and allow the addition of BnCH2MgBr. Substrates with a variety of electron-withdrawing groups were investigated as well, identifying that ester substrates are optimal for the 1,6-addition. Two other investigations feature Me-substituted olefin substrates and substrates with all possible olefin geometries. These studies show unprecedented high enantioselectivity in the 1,6-addition when α-Me substrates are used and give relevant insight into the 1,6-addition mechanism. Finally, substrates with three or four olefins in conjugation with the electron-withdrawing groups were studied. Here, a 1,8-addition is reported that gives the corresponding products in reasonable yield, regio- and stereoselectivity. With the combined results of these studies, elucidating key substrate and reagent parameters, an adapted mechanism for the enantioselective 1,6-addition is proposed. This mechanism features the activation of a dimeric precatalyst by an equivalent of Grignard reagent, active catalyst coordination to the internal olefin of the substrate in a CuI-π-complex, followed by coordination of the catalyst to the remote olefin forming another CuI-π-complex. From the latter CuI-complex, an oxidative addition gives a CuIII-σ-complex at the δ-carbon, followed by transfer of the alkyl moiety to the δ-position. This reductive elimination yields the product and reforms the active CuI catalyst via transmetalation with another molecule of Grignard reagent.
Chiral boronate derivatives via catalytic enantioselective conjugate addition of grignard reagents on 3-boronyl unsaturated esters and thioesters
Lee, Jack Chang Hung,Hall, Dennis G.
supporting information; experimental part, p. 5544 - 5545 (2010/06/14)
-
