Ligands HetPHOX

The development of Ir-chiral N,P ligand system opens another promising way for the hydrogenation of allylic alcohol and its derivatives. For example, a cationic Phox-Ir complex catalyzes the hydrogenation of ( )-2-methyl-3-phenyl-9-propen-l-ol in a highly enantioselective fashion.178 With 1 mol.% (5)-92-Ir catalyst, the hydrogenation proceeds completely to provide the chiral alcohol product in 96% ee. Under the same conditions, a para- Bu-substituted chiral alcohol derivative is obtained with 94% ee for the synthesis of lilial (Equation (59)). Heterocyclic N, P-ligand, HetPHOX 113, is also efficient for this reaction.191... 

The iridium complexes used as precatalysts are air-stable and easy to handle. A further attractive feature is the modular nature of the HetPHOX chiral ligands, which makes it possible to tailor the catalyst structure for a specific substrate. Unfunctionalized and functionalized olefins were hydrogenated with good to excellent enantioselectivity using these iridium complexes and it was possible to obtain also high yield and good enantioselectivity (99% yield, 72% ee.) in the hydrogenation of ( )-phenyl-(l-phenylethylidene)-amine. ... 

Kilroy, T.G., Cozzi, P.G., End, N. and Guiry, P.J. (2004) The application of HETPHOX ligands to the asymmetric intermolecuiar Heck reaction of 2,3-dihydrofuran and 2,2-disubstituted-2,3-dihydrofurans. Synthesis, 1879-88. 

Fitzpatrick, M.O., Coyne, A.G. and Guiry, P.J. (2006) The apphcation of HETPHOX ligands to the intramolecular asymmetric Heck reaction. Synlett, 3150. ... 

As tdready mentioned above, the intermolecular asymmetric catalytic Heck-Mizoroki reaction was first reported by Hayashi [12d,e, 13,15] and since then various groups have made contributions in this area. Of note was the report in 2009 by Guiry s group [57] who achieved enantioselectivities of up to 96% ee, using novel HetPHOX ligands 7a—f for the benchmark reaction with cydohexenyl, phenyl, and 2-naphthyl triflate with 2,3-dihydrofuran (Scheme 1.21). The problem with this reaction is the extensive reaction time (7 days) at the elevated temperature of 80 °C. The kinetic product 8 (or... 

Scheme 1.21 Asymmetric Heck-Mizoroki reactions using HetPHOX ligands as reported by Fitzpartick et al. [57],...

The asymmetric version of this reaction has been carried out using nitrone 46a and terminal alkynes 48 in the presence of HETPHOX 49 ligand as catalyst to afford the -lactams 50 in good diastereoselectivity but moderate enantioselectivity (Scheme 3.19) [52]. Diastereoselectivity of the products depends on the nature of the alkynes. Most alkynes afforded the ds-adducts, whereas trans-products were obtained with the 3,5-trifluoromethylacetylene. Very recently, Chen and coworkers [53] reported a novel efficient catalyst, TOX [chiral tris(oxazoHne)] 51/Cu(I) complex, for the asymmetric Kinugasa reaction of terminal alkynes 48a with C-aryl nitrones 46 to afford the isomeric fi-lactams 52 and 53 in highly enantio- and diastereoselective manners (Scheme 3.20). The highly enantioselective Kinugasa reaction of nitrones 46 with terminal alkynes 48a in the presence of IndaBox 54/Cu(OTf)2 and dibutylamine has been reported to yield the isomeric P-lactams 52 and 53 (Scheme 3.21) [54]. 

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