Atropisomeric phosphines

Ruthenium is cheaper than Rh and chiral Ru complexes have been well investigated in asymmetric work. Usually, lower induction occurs than with the corresponding Rh complexes . However, Ru complexes involving atropisomeric phosphine ligands prove superior to their Rh counterpart in many cases, and become more frequently used . 

Other atropisomeric phosphines 3.45 have been recommended as ligands in rhodium-catalyzed asymmetric hydrogenations of prochiral a,[3-unsaturated acids or esters [892, 904] when R = c-CgHj or in rhodium-catalyzed asymmetric isomerization of allylamines 3.44 [905] when R = Ph. These phosphines 3.45 (R = Ph or c- CgHj j) are interesting ruthenium ligands in asymmetric hydrogena-... 

Among the rhodium complexes, the catalyst containing the nonsymmetrical atropisomeric phosphine-phosphite chelating ligand (1) gave the best enantioselec-tivity (up to 92% ee) in the hydroformylation of the ibuprofen precursor 4-isobutyl-styrene [2] whereas the use of the bulky diphosphite ligand 2 resulted in a remarkable regioselectivity with a branched/normal ratio of 98.5/1.5 and somewhat lower optical yield (82% ee) [3]. 

A new class of phosphines (30) containing only an axial element of chirality (atropisomerism) has been made (253, 254). An in situ 1 1 rhodium/2,2-bis(diphenylphosphinomethyl)-1,1 -binaphthyl system (30a) hydrogenated a-acetamidocinnamic acid to a 54% ee (S) using 50 atm H2, the solvent not being recorded (253). The corresponding diphenyl-phosphinite system (30b) in toluene-acetone was particularly effective (76% ee) for hydrogenation (95 atm) of a-acetamidocinnamic and a-acet-amidoacrylic esters (254). 

The sulfonated atropisomeric bisphosphine MeOBIPHEP (48) was prepared in a Grignard reaction of the appropriate bisphosphonic dichloride and p-indolylsulfonamido-bromobenzene followed by reduction of the phosphine oxide with HSiCU [52]. The indolylsulfonyl protecting group was... 

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... 

However, soluble metal chiral complex catalysts are better, even though ketone hydrogenation under these conditions is more difficult to run than olefin hydrogenation. Notable achievements have been made using Rh and Ru metals. Phosphine ligands are often used, which contain either an asymmetric alkyl group have the phosphorous atom as the asymmetric center, or have an axial element of chirality (atropisomerism) . Other chiral ligands commonly used are derived from amino acids, from L-hydroxyproline and from ferrocene. 

The homogeneous hydrogenation of functionalized carbonyl compounds gives remarkable results with catalysts of the type RUX2L (X = halide, L = atropisomeric ligands). These bis(trialkyl phosphine) ligands have a C2 axis. BINAP is their main representative. ... 

Diphosphine diversity was also exploited by atropisomeric biphenyl ligands. An interesting approach toward water solubilization was disclosed for one of these BINAP-type diphosphines (Scheme 1, MeOBIPHEP-S) [12] (cf. Section 3.2.1). The indolylsulfonyl group withstands the Grignard reaction and phosphine oxide re-... 

A chiral Ir(I) catalyst derived from the amino-(2,2 -biphenoxy)phosphine 37 promotes the synthesis of optically active 3-amino-l-alkenes from 2-alkenols, which are activated by (Eto)5Nb/ l-Vinyl-l,2,3,4-tetrahydroisoquinolines are obtained in good yields in the Pd-catalyzed process. Enantioselectivity is induced by the atropisomeric 38. ... 

In 1980, Professor Noyori and the late H. Takaya consequently designed and synthesized a bidentate phosphine ligand BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthyl) 5, that contained an atropisomeric l,l -binaphthyl structure as a chiral element for use in transition metal catalyzed asymmetric hydrogenation reactions (Figure 1). 

The synthesis of atropisomeric biphenylyldiphosphines has been reviewed. The ferrocenyldiphosphine (115) has been prepared by treatment of l,T-dilithio-ferrocene with an aryl methylphenylphosphinite, and isolated in the form of two diastereoisomers which are separable by recrystallisation from ethanol. Metal-lation of mono- and di-(tetramethylcyclopentadienyl)phosphines, followed by treatment with iron(II) chloride, provides a route to the ferrocenyl systems (116)... 

Full details have now been given of the preparation and characterization of phenylaminophosphines, e.g., (PhNH)3P, from the reaction of dialkylamino-phosphines with aniline, The new atropisomeric chiral diphosphine (72) has been prepared by the reaction of chlorodiphenylphosphine with the appropriate 2,2 -diaminobiphenyl. Related reactions of alcohols and aminoalcohols with chlorodiphenylphosphine have led to several new ligand systems,including the chiral molecules (73) and (74). ... 

Mino et al. recently reported the synthesis of optically pure phosphine ligands 348 and 349 based on atropisomeric N-arylindoles and demonstrated their potency as ligands for palladium-catalyzed asymmetric allylic alkylation (up to 99% ee) (10TA711). 

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