Chiral phosphine-catalyzed enantioselective

Scheme 2.12 Chiral phosphine-catalyzed enantioselective DTHDA cycloaddition of cross-conjugated azatriene, [3]-3-azadendralene.

Zhang et al. developed the enantioselective chiral phosphine-catalyzed addition of 2,3-allenoates with carbon-centered nucleophiles and electron-deficient olefins leading to efficient enantioselective C-C bond formation [248, 249]. 

Among electron-rich chiral phosphines, chiral phospholanes have emerged to be one of the most efficient classes of ligands in metal catalyzed enantioselective reactions. We have developed a novel family of bisphospholane ligand namely, catASium M, from laboratory to commercial scale. Trimethylsilylphospholane 1 was employed as a key intermediate to provide access to a large variety of ligands. 

Kovacik, I., Wicht, D.K., Grewal, N.S., Glueck, D.S., Incarvito, C.D., Guzei, I.A., and Rheingold, A.L., Pt(Me-Duphos)-catalyzed asymmetric hydrophosphination of activated olefins enantioselective synthesis of chiral phosphines,... 

For example, cycloaddition of nitrone (643, R1 =Ph, R2 = Me) to DIO, catalyzed by chiral phosphine-palladium complexes (Fig. 2.42), gave isoxazolidines (644) in high yield with high enantioselectivity (794). 

Simple acyclic a,/ -unsaturated esters are not reactive in the conjugate addition of dialkylzincs. In contrast, nitro-substituted unsaturated esters68 and malonates69 are applicable for this reaction. Using peptide-based chiral phosphine 66, Hird and Hoveyda realized the Cu-catalyzed conjugate addition of Et2Zn to iV-acyloxazolidinones with excellent enantioselectivity (Scheme 21).70... 

It thus came as a surprise that in the year 2000, three groups independently reported the use of three new classes of monodentate ligands (Scheme 28.2) [12], The ligands induced remarkably high enantioselectivities, comparable to those obtained using the best bidentate phosphines, in the rhodium-catalyzed enantioselective alkene hydrogenation. All three being based on a BINOL backbone, and devoid of chirality on phosphorus, these monophosphonites [13], monophosphites [14] and monophosphoramidites [15] are very easy to prepare and are equipped with a variable alkyl, alkoxy, or amine functionality, respectively. 

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

Enantioselective hydrogenation of simple ketones catalyzed by BINAP/chiral diamine-Ru complexes is applied to the synthesis of biologically active compounds and a chiral phosphine ligand. Some examples are shown in Figure 32.44 [85 a, 87, 102, 128, 130, 135],... 

Tillack and co-workers developed a rhodium-catalyzed asymmetric hydrosilylation of butadiyne 258 to afford allenylsilane 260 (Scheme 4.67) [106]. Among more than 30 chiral phosphine ligands investigated, the highest enantioselectivity was observed when the catalyst was prepared from [Rh(COD)Cl]2 (1 mol%) and (S,S)-PPM 259 (2 mol%) to afford the optically active allene 260 with 27% ee. Other metals such as Ir, Pd, Pt or Ni were less effective for example, a nickel catalyst prepared from NiCl2 and (R,R)-DIOP 251 or (S,S)-PPM 259 gave the allene 260 with 7-11% ee. 

In 1990, Alper reported high enantioselectivity of 91% ee using l,T-binaphthyl-2,2 -diylhydrogen phosphate (BNPPA) 91 for the Pd(ii)-catalyzed hydrocarboxylation of 2-vinyl-6-methoxynaphthalene. Several attempts followed that used Pd(ii) catalysts in combination with chiral phosphines 90 or Recently, Hiyama and Nozaki also recorded that... 

Deerenberg, S., Schrekker, H.S., van Strijdonck, G.P.F., Kamer, P.C.J., van Leeuwen, P.W.N.M., Fraanje, J, and Goubitz, K. (2000) New chiral phosphine-phosphite hgands in the enantioselective palladium-catalyzed allylic alkylation. 

The development of chiral peptide-based metal catalysts has also been studied. The group of Gilbertson has synthesized several phosphine-modified amino adds and incorporated two of them into short peptide sequences.[45J,71 They demonstrated the formation of several metal complexes, in particular Rh complexes, and reported their structure as well as their ability to catalyze enantioselectively certain hydrogenation reactions.[481 While the enantioselectivities observed are modest so far, optimization through combinatorial synthesis will probably lead to useful catalysts. The synthesis of the sulfide protected form of both Fmoc- and Boc-dicyclohexylphosphinoserine 49 and -diphenylphosphinoserine 50 has been reported, in addition to diphenylphosphino-L-proline 51 (Scheme 14).[49 To show their compatibility with solid-phase peptide synthesis, they were incorporated into hydrophobic peptides, such as dodecapeptide 53, using the standard Fmoc protocol (Scheme 15).[451 For better results, the phosphine-modified amino acid 50 was coupled as a Fmoc-protected dipeptide 56, rather than the usual Fmoc derivative 52.[471 As an illustrative example, the synthesis of diphe-nylphosphinoserine 52 is depicted in Scheme 16J45 ... 

A rhodium-chiral phosphine complex catalyzes the enantioselective addition of phenylboronic acid to 1-naphthaldehyde to give a chiral diaryl carbinol but with moderate ee (Scheme 13) [39]. When considering the introduction of functionalized aryl groups, arylboronic acid is a promising alternative arylating reagent to diarylzinc compounds. 

The chiral phosphine 31 or 32-rhodium complex catalyzed the addition of arystannanes 30 to N-sulfonylimines 29 to give diarylmethylamines 33 with high enantioselectivity (75-96% ee) [21]. The choice of the chiral monoden-tate phosphine ligand is essential for their catalytic asymmetric arylation. With chelating bisphosphine ligands the arylation was very slow. The authors hypoth-... 

Only limited successful examples of asymmetric hydrogenation of acrylic acids derivatives have included the use of chiral Rh complexes (Scheme 1.17). The diamino phosphine (28) utilizes selective ligation of the amino unit to a Rh center and also exerts electrostatic interaction with a substrate. Its Rh complex catalyzes enantioselective hydrogenation of 2-methylcinnamic acid in 92% optical yield [116], Certain cationic Rh complexes can attain highly enantioselective hydrogenation of trisubstituted acrylic acids [ 1171. 2-(6 -Methoxynaphth-2 -yl)acrylic acid is hydrogenated by an (.S ..S )-BIPNOR- Rh complex in methanol at 4 atm to give (.S)-naproxen with 98% ee but only in 30% yield [26]. 

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