Pfaltz ligand

Initial experiments showed that the asymmetric Heck cyclization of 13 can be realized with several chiral enantiopure ligands. For this transformation, the Pfaltz ligand 14 proved optimal providing the dienyl carbamate 15 in an enantioselectivity of 99 % ee. This Heck cyclization is slow under traditional heating (requiring more than 70 h at 100 °C) but can be accomplished in 30 min with no decrease of enantioselectivity at 170 °C in a microwave reactor. Addition of an excess of trifluoroacetic acid to the crude product furnishes (dihydro-iminoethano)carbazole 15 in 75 % yield over two steps. 

In another beautiful application, Overman et al. developed the total synthesis of the natural product (+)-minfiensine (130), having a l,2,3,4,-tetrahydro-9a,4a-(iminoethano)9H-carbazol core (Scheme 7.29) [80]. The key step in their synthesis is a tandem process consisting of a catalytic asymmetric Mizoroki-Heck ring closure and an N-acyliminium ion cyclization of dienyl carbamate triflate 127 (127—>128). The reaction proceeded smoothly using the Pfaltz ligand (S)- Bu-PHOX (85), providing (dihydroiminoethano)carbazole 129 after the addition of excess trifluoroacetic acid, with 75% overall yield and 99% enantiomeric purity (127 129). 

Excellent enanboselectivibes 19696 ee) for 2-cyclobexenone were also obtained witli tlie ligands 22, 23, and 29, introduced by tlie groups of Pfaltz [47], Reetz [48], and Alexakis [63], respectively. Fes in tlie range of 90-92 96 were found witli ligands 24, 25, 30, and 35 [49, 55, 60]. 

Chiral C2-symmetric semicorrins (structure 4), developed by Pfaltz [11], were proven to be highly efficient ligands for the copper-catalyzed enantio-selective cyclopropanation of olefins. Variations of the substituents at the stereogenic centers led to optimized structures and very high enantioselectiv-ities [12]. 

The first catalytic 1,4-addition of diethylzinc to 2-cyclopentenone with over 90% ee was described by Pfaltz and Escher, who used phosphite 54 with biaryl groups at the 3,3 -positions of the BINOL backbone.46 Chan and co-workers achieved high enantioselectivity in the same reaction (up to 94% ee) by using chiral copper diphosphite catalyst (R,R,R)-41 48,48a 48d Hoveyda and co-workers used ligand 46 to realize excellent enantiocontrol (97% ee) in the 1,4-additions of 2-cyclopentenones,52 which may be used in the practical asymmetric synthesis of some substituted cyclopentanes (including prostaglandins). 

Just as Wilkinson s catalyst gave rise to the bisphosphine ligands, Crabtree s catalyst [304] spawned the family of phosphorus-nitrogen ligands for simple al-kenes. Subsequently, Pfaltz developed the Phox family, which provides high ee-values with nonfunctionalized alkenes [305-310]. Other analogues are also illustrated in Figure 23.5. 

Use of chiral semicorrins and related nitrogen heterocyclic compounds as chiral ligands in asymmetric catalysis has been reviewed periodically. Interested readers are referred to the review by Pfaltz.102... 

G. Helmchen, A. Pfaltz, Phosphinooxazolines - A New Class of Versatile, Modular RN-Ligands for Asymmetric Catalysis, Acc Chem. Res. 2000, 33, 336-345. 

R. Hilgraf, A. Pfaltz, Chiral Bis(N-tosylamino)phosphine-and TADDOL-Phosphite-Oxazolines as Ligands in Asymmetric Catalysis, Synlett, 1999,11,1814-1816. 

O. Loiseleur, M. Hayashi, M. Keenan, N. Schmees, A. Pfaltz, Enantioselective Heck Reactions using Chiral PN-Ligands, J. Organomet. Chem. 1999, 576,16-22. 

Q.-L. Zhou, A. Pfaltz, Chiral Mercaptoaryl-oxazolines as Ligands in Enantioselective Copper-Catalyzed 1,4-Additions of Grignard Reagents to Enones, Tetrahedron, 1994, 50, 4467-4478. 

Pfaltz and co-workers (45) reported neutral variants of the semicorrins as ligands in this reaction. These ligands, termed 5-azasemicorrins, may be readily assembled from pyroglutamic acid in high overall yields. Azasemicorrin (68) complexed to CuOTf forms an effective catalyst for this reaction exhibiting selectivities intermediate between the semicorrins and neutral bis(oxazolines) (45). 

The use of bis(oxazoline) ligands in the Kharasch-Sosnovsky reaction proved to be beneficial, affording well-behaved catalysts. The original investigations were communicated independently and concurrently by Pfaltz and co-workers (108) and Andrus et al. (109). 

Pfaltz and co-workers (108) reported that the allylic oxidation of cyclohexene proceeds in moderate selectivity using stoichiometric amounts of semicorrin-Cu(II) complexes. In catalytic reactions, the enantioselectivity decreased drastically. Better results were realized using bis(oxazolines) as ligands. Upon... 

Zhou and Pfaltz (149) note that complex 215 mirrors the behavior of van Koten s complex 210. The catalyst is trimeric in solution and solid state and displays an intricate nonlinear effect (78, 146) in the conjugate addition reaction, Fig. 19 (149). It seems likely that these ligand-metal complexes are structurally related. 

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