MOD-DIOP

In contrast to the many successful examples for hydrogenation of the parent itaconic acid or its dimethyl ester, only a few ligands have been reported to be efficient for the hydrogenation of / -substituted itaconic acid derivatives. Rh complexes with chiral ligands such as MOD-DIOP,69,69a 69h BPPM,246 Et-DuPhos,247 and TangPhos116 are... 

During the 1980s, Achiwa and colleagues examined a number of derivatives of DIOP, and found that MOD-DIOP (12c) allowed for the enantioselective hydrogenation of itaconic acid derivatives with >96% ee [68-75]. 

The electronic properties around the phosphorus atom can be varied by manipulation of the groups on that atom. MOD-DIOP (12c) was developed by Achiwa and used to reduce itaconic acids [68-72, 75, 103]. Some variations built on BCPM (18e), itself a variant of BPPM, such as the MOD-BCPM (18f) and MCCPM (18g) [88-93, 95-98, 104]. Other variants are PYRPHOS (21a also called DeguPHOS) [105, 106], DPCP (22) [107], NorPhos (23) [108], BDPP (24a) (also called SkewPHOS) [109-111], and PPCP (25) [112]. 

The activity and enantioselectivity of chiral Ir catalysts have been tested by using 2,3,3-trimethylindolenine as a model substrate. Hydrogenation of the cyclic imine with [Ir(bdpp)Hl2 2 gives the corresponding chiral amine with 80% ce (Scheme 1.99) [350]. The stereoselectivity is somewhat better than that with acyclic substrates (see Scheme 1.94). A neutral BCPM-Ir complex with Bil3 effects asymmetric hydrogenation in 91% optical yield [354], A complex of MCCPM shows similar enantioselection [354], These complexes are not applicable to the reaction of other acyclic and six-membered cyclic imines. An MOD-DIOP-Ir complex is also usable with the aid of ( -C4H9)4NI [355], An Ir complex of BICP with phthalimide effectively... 

Of the (at that time) standard ligands tested, only MOD-DIOP gave promising results. 

The enantioselectivity of the hydrogenation of the N-l benzyl-substituted analogue with both (R)-(S)-PPF P (Bu)2 and (4R,5R)-MOD-DIOP is very impressive. None of the undesired 3aR,6aS enantiomer could be detected with the NMR method used. 

The very high enantioselectivity of the hydrogenation of the 1-benzyl intermediate, even with the conventional MOD-DIOP ligand was probably the most impressive result. Development of the process with the N-l benzyl substituent would have made the later intermediates of the biotin process identical to those in the existent commercial process, which could have expanded the market opportunities... 

Achiwa et al. [46,47,48,49] further developed the approach to access the monobutyrolactone skeleton by creating a very efficient catalytic asymmetric method. Aryldensuccinic acid mono-methyl esters (23), obtained by Stobbe condensation of dimethyl succinate and the corresponding substituted aldehydes, were enantioselectively hydrogenated using a neutral rhodium (I) complex of (4[Pg.550]

Using 4 mol % of Pd(dba)2 plus 4 mol % of a chiral phosphine ligand such as BINAP, DIOP, MOD-DIOP, and ferrocenyl phosphines, the reaction of Phi, ( )-l-phenyI-I,2-butadiene, and sodium dimethyl malonate afforded chiral nonracemic (5)-dimethyl 1-methyl-2,3-diphenylallyl malonate 69 with up to 96% ee (Scheme 26)3" ... 

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