Biaryl chiral ketone

In 1999 and 2002, Denmark and coworkers reported several 7-membered carbo-cyclic biaryl chiral ketones (22a-d) (Scheme 3.17) [6a, 22]. For these ketones the chirality is closer to the reacting carbonyl compared with 11-membered ketone 9, which could further enhance the stereodifferentiation for the epoxidation. It was found that the epoxidation rate was greatly accelerated by fluorine substitution at the aorbon... 

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine by asymmetric intramolecular Ullmann coupling or Fe(m)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer.38 Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP, was introduced by Moran, and is found to be effective for the Ru-catalyzed hydrogenation of aryl ketone.39... 

Since ketone R)-16 was prepared in a non-selective way when an achiral imino enolate was alkylated, it was considered whether alkylation of chiral enolates, such as that of oxazoline 18, with benzyl bromide 14, would provide stereoselective access to the corresponding alkylation product 19 with R-configuration at C(8) (Scheme 4). Indeed, alkylation of 18 with 14 gave the biaryl 19 and its diastereoisomer almost quantitatively, in a 14 1 ratio. However, reductive hydrolysis using the sequence 1. MeOTf, 2. NaBH4, and 3. H30", afforded hydroxy aldehyde 20 in 25% yield at best. Furthermore, partial epimerization at C(8) occurred (dr 7.7 1). An alternative route, using chiral hydrazones, was even less successful. 

I.4.I.2. Amino, Hydroxy, and Phenylthio Ketones Asymmetric hydrogenation of amino ketones, in either a neutral or hydrochloride form, has extensively been studied. Both Rh(I) and Ru(II) complexes with an appropriate chiral diphosphine give a high enantioselectivity. As described in Scheme 1.42, a-aminoacetophenone hydrochloride is hydrogenated using a cationic Rh complex with (R)-MOC-BIMOP, an unsymmetricaJ biaryl diphosphine, to give the... 

In 2003, Molander reported the synthesis of (+ )-isoschizandrin using the Sml2-mediated 8-endo-trig carbonyl-alkene cyclisation of ketone 71 (Scheme 7.30).69 The axial chirality of the biaryl system efficiently controls the central chirality of the product. The (Z)-alkene geometry is also vital to the stereochemical outcome and the presence of HMPA in the reaction mixture helps control the conformation of the transition state by increasing the steric demands of the alkoxysamarium substituent.69... 

D. The use of chiral oxazaborolidines as enantioselective catalysts for the reduction of prochiral ketones, imines, and oximes, the reduction of 2-pyranones to afford chiral biaryls, the addition of diethylzinc to aldehydes, the asymmetric hydroboration, the Diels-Alder reaction, and the aldol reaction has recently been reviewed.15b d The yield and enantioselectivity of reductions using stoichiometric or catalytic amounts of the oxazaborolidine-borane complex are equal to or greater than those obtained using the free oxazaborolidine.13 The above procedure demonstrates the catalytic use of the oxazaborolidine-borane complex for the enantioselective reduction of 1-indanone. The enantiomeric purity of the crude product is 97.8%. A... 

Using a chiral auxiliary via an amide or ester leads to asymmetric induction. Aryl aldehydes and conjugated ketones were condensed using proline, leading to modest enantioselectivity. °° Chiral biaryl catalysts have been used with trialkyl-phosphines, giving good enantioselectivity. ° Chiral quinuclidine catalysts lead to... 

The possibihty of chiral modiflcation of NaBH4 for reduction of ketones has been scrutinized. Some success is reported by adding the inexpensive cychc borinate 183 derived from tartaric acid and PhB(OH)2 to the reaction medium. Atropo-enantioselective reduction of biaryl lactones occurs on exposure to NaBH in the presence of the cobalt chelate 184. ... 

Asymmetric hydrogenations of prochiral dehydroamino acid derivatives, enamides, imines, keto esters, and ketones in the presence of synthesized electron-donating phos-phocyclic phosphine ligands and modular atropisomeric biaryl phosphine chiral ligands were reviewed " ... 

More recently, the asymmetric hydrosilylation of aryl ketones and aryl imines has been developed using copper catalysts. " In this case, axially chiral biaryl bisphos-phine ligands boimd to copper generate remarkably active catalysts for tihe hydrosilylation of ketones. These reactions occur with high selectivity using the hydrosilane polymer... 

In a particularly striking example of the broad applicability of OAB methodology, racemic ketones and biaryl lactones have been resolved kinetically to provide the corresponding ketones and lactones with high enantioselectivities [77-79]. Reduction of a racemic ketone 53 using ent-2b- BHj (0.6 equiv.) in THF at -78 C for 30 min provided (-t)-54 in 38% yield, leaving unchanged (-)-53 with 89% ee in 40% yield (Scheme 11.16) [77]. Reduction of racemic ketone 55 under identical conditions, followed by oxidation of each of the product chiral alcohols 56 with PCC, provided (-)-55 (98% ee) and (+)-55 (82% ee) [78]. Similarly, kinetic resolution of racemic 7-mem-bered biaryl lactone 57 with BH3-THF (4.0 equiv.) in the presence of 2b (3.0 equiv.) in THF at -20 C provided (-t )-57 (87% ee, 46% yield) (79). 

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