Mixtures of chiral and achiral monodentate ligands in asymmetric Rh-catalyzed olefin hydrogenation: reversal of enantioselectivity

The recently described method of combinatorial asymmetric transition metal catalysis based on the use of mixtures of chiral monodentate P-ligands has been extended to include mixtures of chiral and achiral monodentate P-ligands, reversal of enantioselectivity in Rh-catalyzed olefin hydrogenation being possible in appropriate cases.     

Pd-catalyzed asymmetric allylic alkylation of glycine imino ester using a chiral phase-transfer catalyst

Pd-catalyzed asymmetric allylic alkylation of the glycine imino ester 1a has been developed using a chiral quaternary ammonium salt 3d without chiral phosphine ligands. The proper choice of the achiral Pd ligand, P(OPh)3, is important to achieve high enantioselectivity. By this method with the dual catalysts, numerous enantiomerically enriched alpha-allylic amino acids 4a-h could be prepared with comparable to higher enantioselectivity than that of the conventional asymmetric alkylation of 1a. In addition, the Pd-catalyzed reaction of 1a with 1-phenyl-2-propenyl acetate 2i afforded the branch product 6 with high enantio- and diastereoselectivity (>95% de, 85% ee).     

Palladium-catalyzed asymmetric hydrosilylation of styrenes with trichlorosilane

Asymmetric hydrosilylation of styrenes with trichlorosilane catalyzed by palladium complexes coordinated with chiral monodentate phosphorus ligands produces chiral benzylic silanes, which can be converted into enantiomerically enriched benzylic alcohols by a stereospecific oxidative cleavage of the carbonsilicon bond with retention of configuration. Due to its high catalytic activity and perfect regioselectivity without producing any by-products, it has recently become a potent methodology to prove the efficacy of newly-developed chiral ligands, especially monodentate ones, in asymmetric synthesis.     

Regio- and stereoselectivity in the reactions of organometallic reagents with an electron-deficient and an electron-rich vinyloxirane: applications for sequential bis-allylic substitution reactions in the generation of vicinal stereogenic centers

Vinyloxiranes provide opportunities for bis-allylic substitution reactions and the generation of new vicinal stereogenic centers if regio- and stereocontrol can be achieved. Ethyl (E)-4,5-epoxy-2-hexenoate affords excellent S(N)2':S(N)2 regioselectivity and anti:syn product diastereoselectivity with dialkyzinc reagents in the presence of CuCN, and conversion of the resultant allylic alcohol to the acetate affords good syn:anti product diastereoselectivity in S(N)2'-selective allylic substitutions with alkylcyanocuprates in THF. (E)-1-(tert-Butyldimethylsilyloxy)-2,3-epoxy-4-hexenonate gives excellent S(N)2':S(N)2 regioselectivity and anti:syn product diastereoselectivity with dialkyzinc reagents in THF or DMF or Grignard reagents in Et(2)O/THF (10/1) in the presence of CuCN. Conversion of the product allylic alcohol into the allylic phosphate affords excellent S(N)2' regioselectivity and syn:anti product diastereoselectivity with lithium alkylcyanocuprates for primary and secondary alkyl transferable ligands, while S(N)2 regioselectivity is observed for the tert-butyl ligand. Reaction conditions have been developed for regio- and stereocontrolled bis-allylic substitution reactions on both electron-rich and electron-deficient alkenyloxiranes, providing a methodology for the generation of vicinal alkane stereogenic centers.     

Ene reaction of singlet oxygen,triazolinedione, and nitrosoarene with chiral deuterium-labeled allylic alcohols: the interdependence of diastereoselectivity and regioselectivity discloses mechanistic insights into the hydroxy-group directivity

The ene reaction of singlet oxygen ((1)O(2)), triazolinedione (TAD), and nitrosoarene, specifically 4-nitronitrosobenzene (ArNO), with the tetrasubstituted 1,3-allylically strained, chiral allylic alcohol 3,4-dimethylpent-3-en-2-ol (2) leads to the threo-configured ene products in high diastereoselectivity, a consequence of the hydroxy-group directivity. Hydrogen bonding favors formation of the threo-configured encounter complex threo-EC in the early stage of ene reaction. For the analogous twix deuterium-labeled allylic alcohol Z-2-d(3), a hitherto unrecognized dichotomy between (1)O(2) and the ArNO and TAD enophiles is disclosed in the regioselectivity of the tetrasubstituted alcohol: Whereas for ArNO and TAD, hydrogen bonding with the allylic hydroxy group dictates the regioselectivity (twix selectivity), for (1)O(2), the cis effect dominates (twin/trix selectivity). From the interdependence between the twix/twin regioselectivity and the threo/erythro diastereoselectivity, it has been recognized that the enophile also attacks the allylic alcohol from the erythro pi face without assistance by hydrogen bonding with the allylic hydroxy functionality.     

The complexity of catalysis: origins of enantio- and diastereocontrol in sulfur ylide mediated epoxidation reactions

The reaction of chiral sulfur ylides with aldehydes and ketones has emerged as a useful asymmetric process for the synthesis of epoxides. Processes employing either catalytic or stoichiometric amounts of sulfides have been developed. Although a large number of chiral sulfur ylides have been tested in the epoxidation process, only a few have delivered high diastereo- and enantio- selectivity. This review examines the factors that influence stereocontrol (steric hindrance of the sulfide, ylide conformation, ylide face selectivity, reversibility of betaine formation, solvent, and metal salts). This analysis leads to the conclusion that high reversibility in betaine formation leads to high diastereoselectivity but low enantioselectivity, and non-reversible betaine formation leads to low diastereoselectivity and high enantioselectivity (provided that other criteria are met). To achieve both high diastereoselectivity and high enantioselectivity simultaneously, requires non-reversible formation of the anti-betaine and reversible formation of the syn-betaine. Thus, factors that influence the degree of reversibility in betaine formation are critically important since with subtle changes in reaction conditions (solvent, temperature, metal ions) both high enantio- and diastereoselectivity can often be achieved.     

Enantioselective syn-selective scandium-catalyzed ene reactions

An enantio- and diastereoselective carbonyl-ene reaction catalyzed by chiral scandium pyridyl bis(oxazoline) (pybox) complexes has been developed. Uniformly high enantiomeric excesses and good yields were observed. Use of trisubstituted olefins generated the syn product in high enantio- and diastereoselectivity.     

Novel rhodium catalyst for asymmetric hydroformylation of styrene: Study of electronic and steric effects of phosphorus seven-membered ring ligands

The asymmetric hydroformylation of styrene catalysed by rhodium complexes modified by monodentate phosphepine ligands has been investigated. The effects of a systematic variation of the phosphorus substituent on catalytic activity and selectivity are reported as well as the outcome of a combinatorial approach for the formation of mixed ligands complexes with several commercially available ligands. Effective catalytic systems have been devised for the reaction that provide for full conversion within 24 h and regioselectivity up to 96% in the branched aldehyde and enantioselectivities up to 48%. The use of bidentate ligands built up by binaphthyl-supported seven-membered phosphacyclic units does not allow for further improvement in the reaction outcome.     

Kinetic and thermodynamic preferences for the diastereoselective oxidative addition of H(2) to trans-Ir(PR(3))(2)(CO)Cl: monodentate chiral phosphines may impart exceptional degrees of diastereoselectivity

Studies on square planar iridium complexes of the type trans-Ir(PR(3))(2)(CO)Cl, where PR(3) is PhP[(C(5)Me(4))](2), PhP[Me(2)C(4)H(6)], or PhP[Pr(i)(2)C(4)H(6)], demonstrate that monodentate chiral phosphines impart exceptional degrees of diastereoselectivity in the oxidative addition of H(2). Thus, the oxidative addition of H(2) to the two faces of the meso isomer (R,S)-trans-Ir(PR(3))(2)(CO)Cl proceeds with a kinetic diastereoselectivity which exceeds that for related square planar iridium complexes employing bidentate chiral phosphine ligands. Furthermore, the kinetically favored dihydride is not favored thermodynamically, and the magnitude of the inversion of the kinetic and thermodynamic selectivities is greater than has previously been observed using bidentate phosphines.     

Combinatorial transition-metal catalysis: mixing monodentate ligands to control enantio-, diastereo-, and regioselectivity

This review focuses on a new approach to combinatorial homogeneous transition-metal catalysis which goes beyond the traditional parallel preparation of modular ligands. It is based on the use of mixtures of monodentate ligands L(a) and L(b), which upon exposure to a transition metal (M) form not only the two homocombinations [ML(a)L(a)] and [ML(b)L(b)], but also the heterocombination [ML(a)L(b)]. If the latter is more reactive and selective than the homocombinations, an improved catalyst system is formed without the need to synthesize new ligands. Thus, the control of enantio,- diastereo-, and regioselectivity is possible.     

Asymmetric construction of chiral C-N axes through rhodium-catalyzed 1,4-addition

Catalytic asymmetric construction of chiral C-N axes has been developed through a rhodium-catalyzed asymmetric 1,4-addition reaction. Both central chirality and axial chirality have been controlled at the same time using Rh/(R,R)-Ph-bod^∗ catalyst with high enantio- and diastereoselectivity. This method has also been applied to the preparation of a planar-chiral ferrocene derivative. The resulting chiral C-N axis can be used as a good template to control the stereochemistry in the subsequent transformations such as alkylation and Diels-Alder reactions.     

Achiral tetrahydrosalen ligands for the synthesis of C(2)-symmetric titanium complexes: a structure and diastereoselectivity study

Achiral tetrahydrosalen ligands have been employed in the synthesis of chiral C(2)-symmetric titanium complexes. When combined with tetrahydrosalen ligands 2a and 2b, titanium tetraisopropoxide liberated 2 equiv of isopropyl alcohol and generated the (tetrahydrosalen)Ti(O-i-Pr)(2) complexes 3a and 3b. These complexes were shown to be C(2)-symmetric by (1)H and (13)C[(1)H] NMR spectrometry and X-ray crystallography. X-ray structures of 3a and 3b indicate that the bonding of the tetrahydrosalen ligand to titanium is different than the bonding of salen ligands to titanium. Whereas salen ligands usually bind to titanium in a planar arrangement, the tetrahydrosalen is bonded with the phenoxide oxygens mutually trans. When bound in this fashion, the nitrogens of the tetrahydrosalen ligand and the titanium become stereogenic centers. The use of titanium complexes of high enantiopurity in the generation of tetrahydrosalen titanium adducts resulted in a maximum diastereoselectivity of 2:1. The diastereoselectivity obtained using chiral titanium alkoxide complexes was greater than the diastereoselectivity observed when a tetrahydrosalen ligand derived from (S,S)-trans-diaminocyclohexane was employed.     

Asymmetric construction of quaternary carbon centers by regio- and enantiocontrolled allylzincation

An allylic zinc reagent bearing a chiral bisoxazoline ligand adds to a substituted cyclopropenone acetal to produce an optically active cyclopropanone acetal possessing a quaternary chiral center in high yield with 97.8-99.8% ee. The steric effects of the bulky bisoxazoline ligand overwhelm the regioselectivity inherent to the electronic property of the olefinic acceptor. High pressure exerts favorable effects on the reaction rate without affecting the high enantio- or regioselectivity.     

Phosphoramidites: Privileged Ligands in Asymmetric Catalysis

Asymmetric catalysis with transition‐metal complexes is the basis for a vast array of stereoselective transformations and has changed the face of modern synthetic chemistry. Key to this success has been the design of chiral ligands to control the regio‐, diastereo‐, and enantioselectivity. Phosphoramidites have emerged as a highly versatile and readily accessible class of chiral ligands. Their modular structure enables the formation of ligand libraries and easy fine‐tuning for a specific catalytic reaction. Phosphoramidites frequently show exceptional levels of stereocontrol, and their monodentate nature is essential in combinatorial catalysis, where a ligand‐mixture approach is used. In this Review, recent developments in asymmetric catalysis with phosphoramidites used as ligands are discussed, with a focus on the formation of carbon–carbon and carbon–heteroatom bonds.     

Direct catalytic asymmetric method for the synthesis of tetrahydropyranopyrazoles through allene zwitterion chemistry

The enantioselective synthesis of the tetrahydropyranopyrazole scaffold has been achieved. The quinidine catalyzed reaction of allenoates with arylidenepyrazolones proceeded with high enantio- and diastereoselectivity while the reactions of alkylidenepyrazolones were less efficient. Allene ketones also afforded tetrahydropyranopyrazole derivatives in high yields, however, with only moderate enantioselectivity. The primary adduct undergoes further functional group transformations without effecting the initially formed chiral centre.     

Asymmetric synthesis of quaternary centers. Total synthesis of (-)-malyngolide

[structure] The deracemization of 3-nonyl-3,4-epoxybut-1-ene with Pd(0) in the presence of chiral ligands using p-methoxybenzyl alcohol as a nucleophile proceeds regio- and enantioselectively to form the monoprotected vinylglycidol in 99% ee. This chiral building block was converted in seven steps to (-)-malyngolide, an antibiotic showing significant activity against Mycobacterium smegmatis and Streptococcus pyogenes. An interesting aspect involves controlling the diastereoselectivity of protonation of an enolate via a distal hydroxyl group.     

Sequential Birch reaction and asymmetric Ir-catalyzed hydrogenation as a route to chiral building blocks

A range of 1,2,4-trisubstituted cyclohexadienes obtained from the Birch reaction were hydrogenated asymmetrically to produce synthetically valuable chiral compounds in high enantio- and diastereoselectivity.     

Steroid imines as chiral ligands. Diastereoselective formation of (1-azadiene)Fe(CO)3 complexes by sterically tuning the ligand coordination spheres

The condensation of steroid amines with α,β-unsaturated aldehydes leads to the formation of chiral 1-azadiene ligands with a steroid core attached to nitrogen. If the azadiene chain is situated at the D-ring of the steroid at C₁₆ or C₁₇, respectively, the two diastereotopic faces of the ligand may be discriminated by different neighbouring substituents and their configuration. The reaction of these ligands with Fe₂(CO)₉ produces mixtures of diastereomeric (1-azadiene)Fe(CO)₃ complexes. By increasing the steric demands of the neighbouring groups it is possible to improve the diastereoselectivity of this complexation reaction from 1:1 mixtures using the least sterically hindered ligands to complete diastereoselectivity using the azadiene derived from cinnamaldehyde and 16β-amino-3-methoxy-estra-1,3,5(10)-triene-17β-ol. In addition, the molecular structure of [17β-(3-phenyl-prop-2-enyliden)-amino-3-methoxy-estra-1,3,5(10)-triene]Fe(CO)₃ was determined by X-ray structure analysis.     

Organocatalyzed, enantioselective synthesis of bicyclo-[2.2.2]-octanes containing benzylic, all-carbon quaternary centers

Proline aryl sulfonamide-catalyzed, multi-component couplings have been developed for accessing densely functionalized [2.2.2] bicyclic ketones containing up to four contiguous chiral centers including an all-carbon benzylic quaternary center in high enantio- and diastereoselectivity. Application to the bicyclic core of the recently isolated alkaloid kopsonoline is illustrated.     

膦配体修饰的Rh／SiO2用于3-戊烯酸甲酯氢甲酰化反应

制备了膦配体修饰的Rh/SiO2多相催化剂(L-Rh/SiO2),该催化剂在内烯烃氢甲酰化制备正构醛反应中表现出了高活性和高区域选择性,而且在高压釜反应器中可以通过简单的过滤与产物分离.通过使用不同的单齿和螯合双齿膦配体考察了配体的电子及空间效应对L-Rh/SiO2催化剂催化性能的影响。