Phosphines BIPHEP

BINAP system with excellent ee s. For example, 0// 0-bromoacetophenone can be converted into the corresponding chiral alcohol with 96% ee (Equation (72)). However, this type of substrate can be hydrogenated more effectively with the Ru/chiral phosphine/diamine system.279 Asymmetric hydrogenation of phenylthioketones has been realized with Ru catalysts. BINAP, MeO-BIPHEP,280 BDPP281 and Me-CnrPHOS,62c are efficient for this transformation (Table 17). 

The binaphthyl backbone of BINAP has inspired many variations of atropisomeric biaryl bisphosphines. One approach by Roche was to substitute the binaphthyl backbone with a 6,6 -dimethox-ybiphenyl backbone. MeO-Biphep (96a) was synthesized in approximately 26% yield in 6 steps from 3-bromoanisole (97a) (Scheme 12.30). MeO-Biphep can also be synthesized in 5 steps from 2-iodo-3-nitroanisole in approximately 18% yield. Several phosphine analogues can be prepared by the addition of R2PC1 to the lithio intermediate.117... 

One class of ligands that racemizes readily at room temperature is based on atropisomeric bidentate phosphines such as BIPHEP, NUPHOS, and cyclo-NUPHOS (Figure 6). For example, the barrier to racemization of BIPHEP is 22kcalmol , making it very difficult to... 

Further studies on AHR of 2,3-dihydrofuran (286) with phenyl triflate afforded different products with high % ee depending on the ligands used. The isomer 287 with 96 % ee was obtained selectively when the phosphine—oxazoline ligand 291 was used [119]. On the other hand, the isomer (288) with 98% ee was the major product when (5)-MeO-BIPHEP (292) was used [120]. AHR of 283 with 289 using (R)-BITIANP (293, XV-7) in the presence of proton sponge afforded the coupling product 290 with 91 % ee selectively [121]. 

Krische and co-workers have investigated the tertiary phosphine-catalyzed regjospecific allylic amination of MBH acetates through a tandem 5n2 -5n2 mechanism by using phthalimide derivatives as nucleophiles. When (1 )-C1-MeO-BIPHEP was used as a catalyst, the MBH adduct obtained from p-nitrobenzaldehyde and methyl acrylate reacted with phthalimide to give the allylic substituted product 297 in 80% yield with 56% ee (Scheme 3.126). ... 

Further studies were undertaken to develop a second generation of Ugands with a broader scope. After extensive experimentation, it was found that mixed-ligand complexes of the type [Ru(dmpe)(H)(P )]BPh4, containing a dmpe and one chiral diphosphine, gave the best results. The structures of the best two phosphines, MeO-BiPHEP and DIFLUORPHOS are shown in Figure 6.4. 

With the complex containing (R)-MeO-BiPHEP the results with mono- and dibenzylic substrates were similar to those obtained with complex 94 (Table 6.14) but at room temperature instead of at 30 °C. Interestingly, in contrast to 94 it was found that the complex with the phosphine (i )-DIFLUORPHOS is active in the phosphination of aliphatic substrates (Table 6.15). ... 

In 2004, Krische and colleagues demonstrated that exposure of Morita-Baylis-Hillman acetates to tertiary phosphine catalysts in the presence of 4,5-dichlorophthalimide enabled regiospecific allylic substitution through a tandem Sn2 -Sn2 mechanism. Through the use of the chiral phosphine catalyst, (i )-Cl-MeO-BIPHEP, the racemic Morita-Baylis-Hillman acetate depicted in Scheme 2.108 was converted into the corresponding enantiomerically enriched allylic amination product, thus establishing the feasibility of DKR. 

The optimum combination was found to be that of 5.16 as the precatalyst, and MeO-Biphep as the chiral ligand. Under the reaction conditions and in the presence of MeO-Biphep, 5.16 loses COD and both the allyl ligands. The substrate 5.15 coordinates to the metal atom through the carboxylate and alkene functionalities. The chelating phosphine occupies two other coordination sites. The active catalytic intermediate 5.17 formed this way sets up the enantioselective catalytic cycles. 

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