Chiral phosphine-phosphite ligands in the highly enantioselective rhodium-catalyzed asymmetric hydrogenation.

We have investigated a series of enantiopure phosphine-phosphite ligands (P(1)-P(2) = ligands 1-4) in the rhodium-catalyzed asymmetric hydrogenation reaction. Intermediate [Rh(P(1)-P(2))(cod)]BF(4) and [Rh(P(1)-P(2))(5)]BF(4) complexes (cod = 1,5-cyclooctadiene; 5 = methyl acetamidoacrylate ester) were observed by (31)P[(1)H] NMR. The [Rh(P(1)-P(2))(cod)]BF(4) complexes were precursors to active catalysts of the asymmetric hydrogenation reaction of several prochiral dehydroamino acid derivatives under mild reaction conditions (1 bar of hydrogen and 20 degrees C). The enantiomeric excess reached up to 99%.     

An enantioselective synthesis and the absolute configuration of natural pumiliotoxin-C. Preliminary communication

(?)-Pumiliotoxin-C-hydrochloride, as well as its unnatural enantiomer, have been synthesized in an enantioselective manner starting from (S)- or (R)-norvaline, respectively. In the crucial cycloaddition step 11 → 12 (cf. scheme 2) the chiral center of 11 controls to a major extent the three developing centers of chirality. This synthesis shows unambigously the (2S)-configuration of natural pumiliotoxin-C.     

Chiral ruthenabicyclic complexes: precatalysts for rapid, enantioselective, and wide-scope hydrogenation of ketones

A novel ruthenabicyclic complex with base shows excellent catalytic activity in the asymmetric hydrogenation of ketones. The turnover frequency of the hydrogenation of acetophenone reaches about 35,000 min(-1) in the best case, affording 1-phenylethanol in >99% ee. Several aliphatic and base-labile ketones are smoothly converted to the corresponding alcohols in high enantioselectivity. The catalytic cycle for this hydrogenation, in which the ruthenabicyclic structure of the catalyst is maintained, is proposed on the basis of the deuteration experiment and spectroscopic analysis data.     

Chiral phosphoramide-catalyzed enantioselective addition of allylic trichlorosilanes to aldehydes. Preparative and mechanistic studies with monodentate phosphorus-based amides

The addition of allylic trichlorosilanes to benzaldehyde promoted by chiral phosphoramides to give the enantioenriched homoallylic alcohol has been investigated. In a survey of Lewis bases as activators for the addition of allyltrichlorosilane to benzaldehyde, phosphorus-based amides have been found to be the most effective promoters. To achieve asymmetric induction, chiral phosphoric triamides derived from chiral diamines have been developed and applied in the allylation reaction albeit with modest enantioselectivities. The addition of 2-butenylsilanes was highly diastereoselective, suggesting a closed, chair-like transition structure. A detailed mechanistic study has been carried out to probe into the origin of activation. From a combination of nonlinear effects and kinetics studies, the reaction was found to likely involve two phosphoramides in both the rate and stereochemistry determining steps. These studies provided the background for the development of highly selective and reactive catalysts.     

A Novel Asymmetric Benzoin Reaction Catalyzed by a Chiral Triazolium Salt. Preliminary communication

Using the chiral triazolium salt 1 as catalyst, a novel asymmetric variant of the benzoin reaction is reported. For the first time, the scope of the method is extended to a broader range of aromatic aldehydes 2 , affording the acyloins 3a–h in yields of 22–72% and enantiomeric excesses up to 86%.     

A mechanistic study of the hydrogenation of cyclohexene catalyzed by dimethylzirconocene

A kinetic study of the hydrogenation of cyclohexene in the presence of phenylsilane and catalytic amounts of dimethylzirconocene has been carried out. The rate law for the reaction was deduced to be of the form of rate =k[catalyst][silane]^3/2 [olefin]⁰, showing that the catalytically active species would be a hydridosilylzirconium complex formed by the reaction of dimethylzirconocene with phenylsilane     

A versatile new catalyst for the enantioselective isomerization of allylic alcohols to aldehydes: scope and mechanistic studies.

A new planar-chiral bidentate phosphaferrocene ligand (2) has been synthesized and structurally characterized. The derived rhodium complex, [Rh(cod)(2)]BF(4), serves as an effective catalyst for asymmetric isomerizations of allylic alcohols to aldehydes, furnishing improved yields, scope, and enantioselectivities relative to previously reported methods. The catalyst is air-stable and can be recovered at the end of the reaction. Mechanistic studies establish that the isomerization proceeds via an intramolecular 1,3-hydrogen migration and that the catalyst differentiates between the enantiotopic C1 hydrogens.     

Steric effects in the enantioselective transfer hydrogenation of 2-aroylacetates

Benzoylacetate esters and aryl-substituted derivatives are efficiently reduced in 2-propanol using the readily available catalytic combination (1S,2R)-ephedrine/[RuCl₂(η⁶-p-cymene)]₂ to give the corresponding alcohols in high yields and enantioselectivities (up to 94% ee).     

Tetraphosphacubane: An Unexpectedly Strong Base in the Gas Phase

The experimental determination of physical properties of tetra-tert-butylphosphocubane (TtBuPC) is of paramount importance for understanding the reactivity of this fascinating molecule.The gas-phase basicity of TtBuPC measured by FT-ICR spectroscopy (GB = 221.8 kcal mol(-)(1), PA = 230.5 kcal mol(-)(1)) is surprisingly high although protonation in solution is only achieved under drastic conditions. A molecular orbital treatment, including electron correlation effects, predicts the unsubstituted parent compound phosphacubane (PC) to be a carbon base. Carbon protonation implies a P-C bond fission which alleviates the strain of the system. A similar behavior is also predicted for the tetramethyl derivative. However, TtBuPC is found to be a phosphorus base, because the strong repulsive interactions which appear between the tert-butyl substituents destabilize significantly the C-protonated form. These effects decrease dramatically when just one tert-butyl group is removed and both P- and C-protonated species become almost degenerate. As for other strained systems, the PAs of PC and TtBuPC are only adequately reproduced when G2-type [6-311+G(3df,2p)] basis sets are used.     

An efficient synthesis of chiral beta-hydroxy sulfones via ru-catalyzed enantioselective hydrogenation in the presence of iodine

Ru-SUNPHOS catalyzed asymmetric hydrogenation of a variety of sulfonyl ketones (R = alkyl, aryl) in the presence of iodine gave enantioenriched hydroxyl sulfones with good catalytic efficiency. Further investigation revealed that the in situ generated anhydrous HI is the operating additive.     

Chiral amino ether-controlled catalytic enantioselective arylthiol conjugate additions to alpha,beta-unsaturated esters and ketones: scope, structural requirements, and mechanistic implications.

Asymmetric conjugate addition reaction of 2-trimethylsilylbenzenethiol with enoates and enones is catalyzed by a chiral amino ether-lithium thiolate complex and affords adducts with high enantioselectivity. Both the s-cis conformation and a steric wall at one side of the carbonyl group are structural requirements in substrates yielding adducts with high enantioselectivity. Reactions with tert-butyl enones gave addition products with high enantioselectivity. Construction of two contiguous chiral centers was possible by this addition-protonation sequence. Methyl tiglate was stereoselectively converted to a single syn-adduct of 95% enantiomeric excess (ee) bearing two contiguous chiral centers. Methyl 2-phenyl-2-butenoate was converted to a single syn-adduct of 95% ee, which was desulfurized to methyl 2-phenylbutanoate of 95% ee. These additions generate a transient lithium enolate that is protonated by a thiol anti to the C-S bond, giving the corresponding product having two adjacent stereocenters.     

Chiral sulfoxides in the enantioselective allylation of aldehydes with allyltrichlorosilane

The use of chiral sulfoxides as Lewis base catalysts in the allylation of aldehydes with allyltrichlorosilane is reported.     

Probing subtle ligand effects in the enantioselective transfer hydrogenation of ketones

The rational modification of an established amino-alcohol scaffold has revealed new, highly effective ligands for the enantioselective transfer hydrogenation of acetophenone that affords the product in up to 95% ee.     

A structural investigation of the antibiotic rubiflavin. Preliminary communication

Rubiflavin is shown to be a mixture of antibiotics. The main components have been named rubiflavin A (3) and rubiflavin B (2) and are identified by NMR. spectroscopy as desacetylpluramycin A and kidamycin, respectively.     

Asymmetric catalysis. Part 128: Diastereomeric rhodium(I) complexes in the enantioselective hydrogenation of ketopantolactone

In the hydrogenation of ketopantolactone, new rhodium complexes bearing (R,R)-diop and various bidentate chiral N,N′ co-ligands with (R)- or (S)-configuration were used. On the one hand, the N,N′ co-ligands consist of pyrroleimines, which derive from (R)- and (S)-1-phenylethylamine, (R)- and (S)-1-cyclohexylethylamine (and benzylamine), and on the other hand of pyrroleoxazolines and pyridineimines. Stereoselectivities of 31–33% ee for (R)-pantolactone were achieved using related compounds (RR-R) and (RR-S), respectively, with no double stereoselectivity being observed. It is assumed that during catalysis the pyrroleimines bind in a monodentate way at the sixth coordination site of the rhodium atom by the pyrrole nitrogen with the imine nitrogen carrying the different chiral substituents far away from the rhodium atom. Monodentate deltacyclane phosphanes, chloro ligands or solvent molecules, bound at the sixth coordination site of the catalyst, led to widely differing enantioselectivities in the ketopantolactone hydrogenation.     

Tetrathiafulvalene–oxazoline ligands in the iridium catalyzed enantioselective hydrogenation of arylimines

Cationic iridium complexes based on enantiomerically pure tetrathiafulvalene–oxazoline ligands have been used in the asymmetric hydrogenation of N-(phenylethylidene)aniline. Complete conversions with ee’s up to 68% could be reached in the case of the TTF–phosphinooxazoline (TTF–PHOX) ligands.     

High Asymmetric Induction in Conjugate Additions of RCu · BF3 to Chiral Enoates. Preliminary communication

1,4-Additions of PhCu · BF₃, n-Bu · BF₃ and MeCu · BF₃ to the trans-8-phenyl-menthyl enoates 1 proceeded with high chiral induction. Saponification of the resulting esters 2 gave the corresponding enantiomerically pure β-substituted alkanoic acids 3 and the recovered (?)-8-phenylmenthol in good overall yields. Analogous additions to the cis-crotonate 1 led preferentially to the acids 3 enantiomeric to those obtained from the trans-crotonate 1 , although with lower selectivity. A stereochemical model is proposed consistent with the observed results (Scheme 2, Table).