Chiral nonracemic ligands

The enantioselective cleavage of strained ethers (epoxides and oxetanes) by organolithiums, mediated by chiral, nonracemic ligands (as well as additions to aldehydes and ketones), has been reviewed by Goldfuss <2005S2271>. 

In one case (R = phenanthren-9-yl R2 = R3 = ethyl) compound 3 was isolated in 65% chemical yield and an enantiomeric excess of 93%. When the Dane diene 1 reacted with the ethyl substituted diketone 2 (Fig. 25) under the above mentioned conditions (20 mol% of the chiral-nonracemic ligand) 3 was accessible in 77% chemical yield and an enantiomeric excess of 88% [31]. 

The progress of ruthenium-catalyzed cyclotrimerizations is expected to continue with further investigations on novel catalysts with chiral nonracemic ligands, the exploitation of other substrates and reaction media, and applications in underdeveloped areas. As a result, ruthenium-based catalysis will be indispensable for organic synthesis, pharmaceutical research, and materials science. 

Cross-coupling reactions between amines and aryl halides or pseudohalides have been employed for the preparation of a number of chiral, nonracemic ligands for asymmetric catalysis. For example, early studies by Buchwald illustrated that chiral amino binaphthol derivatives could be generated by Pd-catalyzed Af-arylation of binaphthol-derived triflates (Eq. 74) [417]. A similar strategy was employed by Erase for the synthesis of planar-chiral [2.2]paracyclophane ligands (Eq. 75) [418]. The A -arylation of [2.2]paracyclophane-derived triflates has also been used for the construction of planar-chiral benzimidazoles [419]. The IV-arylation of a substituted pyrrolidine with 4-bromopyridine played a key role in the synthesis of a chiral nucleophilic catalyst related to DMAP [420]. 

In recent years, enantioselective variants of the above transannular C-H insertions have been extensively stiidied. The enantiodetermining step involves discrimination between the enantiotopic protons of a meso-epoxide by a homochiral base, typically an organolithium in combination with a chiral diamine ligand, to generate a chiral nonracemic lithiated epoxide (e.g., 26 Scheme 5.8). Hodgson... 

Chiral nonracemic bidentate 2-[o-(diphenylphosphino)phenyl]-5,6-dihydro-4//-l,3-oxazine derivatives proved to be effective P,N-ligands in Pd-catalyzed asymmetric transformations. When used in the Pd-catalyzed allylic alkylations of 1,3-diphenylallyl acetate with dimethyl malonate, phosphino-oxazines 147 and 148 and the... 

The chiral nonracemic bis-benzothiazine ligand 75 has been screened for activity in asymmetric Pd-catalyzed allylic alkylation reactions (Scheme 42) <20010L3321>. The test system chosen for this ligand was the reaction of 1,3-diphenylallyl acetate 301 with dimethyl malonate 302. A stochiometric amount of bis(trimethylsilyl)acetamide (BSA) and a catalytic amount of KOAc were added to the reaction mixture. A catalytic amount of chiral ligand 75 along with a variety of Pd-sources afforded up to 90% yield and 82% ee s of diester 303. Since both enantiomers of the chiral ligand are available, both R- and -configurations of the alkylation product 303 can be obtained. The best results in terms of yield and stereoselectivity were obtained in nonpolar solvents, such as benzene. The allylic alkylation of racemic cyclohexenyl acetate with dimethyl malonate was performed but with lower yields (up to 53%) and only modest enantioselectivity (60% ee). 

A case of matched and mismatched pairs was observed in the reagent-controlled cyclopropanation of chiral allylic alcohols. When the chiral, nonracemic allylic alcohol was treated with one enantiomer of the dioxaborolane ligand, the anti diastereomer was... 

The extraordinarily strong chiral properties of [nfhelicenes provide an impetus for the development of synthetic approaches to nonracemic [nfhelicenes for applications as organic materials. From this point of view, asymmetric syntheses of functionalized long [n]helicenes (n > 7), and also [n]helicene-like molecules and polymers with novel electronic structures and material properties, are important. The properties of helicenes related to materials are relatively unexplored, compared with the more synthetically accessible n-conjugated molecules and polymers. Notably, redox states of helicenes are practically unknown [33, 34]. Assembly of helicenes on surfaces, their uses as liquid crystals, chiral sensors, ligands or additives for asymmetric synthesis and helicene-biomolecule interactions are in the exploratory stages [35-43],... 

Double Diastereoselection in the Dihydroxylation Reaction. The dihydroxylation reaction of chiral nonracemic substrates using the cinchona-derived ligand leads to a matched and mismatched pair (eq 6) Kinetic resolution of several racemic secondary alcohols has also been examined. ... 

In principle a metal atom may also be stereogenic (and therefore influence the stereoselectivity), but a separate category is not needed since chiral nonracemic metal complexes containing achiral ligands are rare in asymmetric synthesis [53]. 

In some cases, it is possible to form a chiral, nonracemic alcohol from a prochiral ketone and a Grignard reagent by adding an asymmetric ligand (a chiral additive) to the reaction mixture, which is differentiated from... 

An alternate approach to the asymmetric alkylation of aldehydes with dialkylzinc compounds uses chiral nonracemic titanium-based Lewis add catalysts. This has been primarily achieved using complexes prepared from stoichiometric amounts of Ti(0 Pr)4 and enantiomerically enriched ligands. A variety of BINOL deriva-... 

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" ... 

Recent refinements in hydride transfer reductions have enhanced the utility of oxazaborolidine- and BINAP-Ru (II) complex-catalyzed reductions. A review by Wills describes the development of catalysts for the syntheses of chiral nonracemic secondary alcohols from aryl ketones [5]. Among the more interesting catalysts discussed were f/ -arene ruthenium complexes, which utilize diamine and monotosylated diamine ligands. 

Tanaka et al. developed a Rh-catalyzed asymmetric one-pot transesterification and [2+2+2] cyclotrimerization using nonracemic ligand 415 in the synthesis of enantio-enriched 3,3-disubstituted phthalides (R R ) (Scheme 2-39)P The chiral Rh complex with 415 efficiently desymmetrized dipropargyl alcohols 413 (R = R -OC-) in the reaction with 412 to give phthalides 414 (R = R -C=C-) in up to 87% yield and 93% ee. Also, the kinetic resolution of racemic tertiary propargylic alcohols... 

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