Low Pressure Asymmetric Hydrogenation of Quinolines using an Annulated Planar Chiral N‐Ferrocenyl NHC‐Iridium Complex

Abstract

Annulated planar chiral N-ferrocenylimidazolones,o btainedb ya cid-mediated cyclization of diphenylmethanol derivatives,m ay be reduced with diisobutylaluminium hydide (DIBAL-H) to afford as eries of surprisingly stable and isolable hemiaminal ether aminals. Tw oo ft hese derivatives can be oxidized with triphenylcarbenium tetrafluoroborate to imidazolinium salt precursors of N-heterocyclic carbenes (NHCs). Deprotonation of these salts in the presenceo f( cyclooctadiene)iridium chloride dimer {[Ir(COD)Cl] 2 }p rovides chiral coordination complexes bearing N-ferrocenyl NHCsw ith unique rigid tetracyclic frameworks.C ationic analogues of these complexes catalyze the asymmetric hydrogenation of 2-substituted quinolines under very mild conditions( 1mol% complex, 1mol% PPh 3 ,1 -5 atm H 2 , toluene,2 5 8 8 C) in appreciable enantioselectivity (up to 90:10 er). Thes ensitivityo ft he hydrogenation process to changes in the phosphineadditive suggests that an outer-sphere reactionm echanism may be involved, as proposed for ar elated achiral NHC-Ir complexr eported by Crabtree and co-workers.

A leap forward in iridium–NHC catalysis: new horizons and mechanistic insights

“…The related NHC-P catalyst 11, showed a significantly lower chiral induction compared to the previously described NHC-N based catalysts. 26 Monodentate NHCs containing chiral backbones have also been studied as ligands for asymmetric hydrogenation, but, in general, modest optical inductions were obtained for their corresponding iridium catalysts 12, 27 13, 28 14, 28 15 29 and 16 30 ( Figure 3). NHC-N Ir complexes presenting a coordinated NH2 moiety (17 and 18, Figure 4) are able to reduce unsaturated polar bonds 31 via an outer-sphere mechanism assisted by an external base, namely isopropoxide, where metal-ligand cooperation 32 plays a key role (Scheme 2).…”

Planar‐Chiral Ferrocene‐Based N‐Heterocyclic Carbene Ligands

“…In the same year, Metallinos and co‐worker reported chiral NHC ( S , S , S p )‐ 53 , the design concept of which is similar to that of 46 (Scheme ) . First, ferrocenyl imidazolone ( R , S )‐ 50 possessing two central chiralities was converted into diphenylmethanol adduct 51 by utilizing the diastereoselective ortho ‐functionalization strategy.…”

“…In the same year,M etallinos and co-worker reported chiral NHC (S,S,S p )-53,t he design concept of whichi ss imilar to that of 46 (Scheme19). [45] First, ferrocenyl imidazolone( R,S)-50 possessing two central chiralities was converted into diphenylmethanol adduct 51 by utilizing the diastereoselective ortho-functionalization strategy.Then, 51 was subjected to acid-mediated cyclization to form ad iastereomeric mixture of anti-a nd syntetracyclic ferrocenes 52 (4:1), which were purifiedb yf lash columnc hromatography on silica gel. Ar eaction sequence that included reduction with DIBAL-Ha nd oxidationw ith triphenylcarbenium tetrafluoroborate of separated anti-52 afforded carbene precursor [53H]BF 4 ,b ut it was not isolable owing to instability.…”

Diastereoselective Lithiation of N-Benzyl Pyrroloimidazolones Derived from l-Proline Hydantoin

“…In this paper, we report the diastereoselective lithiation of the prochiral sp 3 -hybridized N-benzyl position of chiral imidazolone 9, determine the stereochemistry of the products after electrophile quench, and investigate whether the reaction proceeds by an asymmetric deprotonation or asymmetric substitution pathway. This type of chiral auxiliary, which contains a labile aminal ether, has thus far only been used to induce planar chirality via deprotonation of sp 2 -hydridized carbons in ferrocenes [17][18][19] (e.g., syn-8) and η 6 -arene chromium tricarbonyl complexes, 20 where configurational stability of the intermediate anions is not in question. The preliminary results on substrate 9 may provide incentive to study pyrroloimidazolone chiral auxiliaries for stereoselective lithiation-substitution of other substrates with prochiral N-sp 3 positions that are not within rings.…”