Phebox

Introduction of 3,5-dimethyl and 4-substituent on the Phebox skeleton revealed a weak substituent effect on the degree of asymmetric induction (Scheme 15) [28,29]. When trimethylsilyl acrylate was used as enolate source, the (3-hydroxy carboxylic acid was obtained directly upon mild acid hydrolysis. In the production of carboxylic acid 49, an enantiomeric excess of 96% ee was attained using the NC -substituted Phebox-Rh catalyst. 

The catalytic system of Rh(Phebox) and MePl SiH was applied to the coupling of acetone and cinnamates under solvent-free conditions (Scheme 16) [30]. Several cinnamates and crotonates were used as enolate... 

Scheme 15 Asymmetric reaction catalyzed by substituted-Phebox-Rh...

Scheme 16 Rh(Phebox) catalytic system toward ketones...

New 4-substituted phenyl(bisoxazoline) ligands (PHEBOX ligands) have been com-plexed with rhodium and examined as enantioselective catalysts of the reductive aldol of acrylates and aldehydes.160 The results have been compared with the corresponding pyridine-centred (PYBOX) ligand complexes. 

Catalysts with nitrogen ligands such as bisoxazolines76 have been introduced as Fewis acids. Recently, air-stable and water-resistant (Phebox)rhodium(III) 9 complexes gave up to 80% ee77. 

The complexes (5,5)-(Phebox)Pt(OTf) and [(5,5)-(Phebox)Pt(H20)](BF4) react with A -phenylbenzaldimine to afford the corresponding chiral aldimine complexes. Addition of organolithium reagents gives, after work-up, the corresponding enantio-merically enriched amines (Sch. 34) [145],... 

Fig. 5 Crystal structures of active site of artificial metalloproteins a Cu(Sal-Phe) apo-Mb, and b Rh Phebox apo-A71G Mb taken from PDB ID 2EB8, and 2EF2, respectively...

Taylor et alP applied an asymmehic variant of this reaction using a Rh-BINAP catalyst and aldehydes, e.g., 296, as aeceptors to yield aldol produets sueh as 298. Although a variety of aromatie, eyelie, and acyelic aldehydes was effective acceptors, the scope of the o,P-unsaturated ester was limited to phenyl acrylate 297, and the enantioseleetivity and syn/anti seleetivities still need to be improved. Shiomi et reported an asymmetrie reduetive eoupling reaction of enones and aromatic aldehydes using ehiral Rh(Phebox) catalysts. Diphenylmethylsilane was used as a hydride donor in this ease, and the desired P-hydroxyketones were produced with up to 93% ee. 

Goldberg, Heinekey, Goldman, and coworkers have recently made progress towards achieving this goal. They found that the Ir(III) bis-acetate complex ( hebox)Ir(OAc)2(OH2) ( phebox = 2,6-bis(4,4-dimethyloxazolinyl)-3,5-... 

---