Enantioselective control

Bonnemann, H. and Braun, G.A., Enantioselectivity control with metal colloids as catalyst, Chem. -Eur. J., 3, 1200, 1997. 

In Heading 1.4 we have already seen that three different kinds of control elements [3] may be considered 1) chemoselective control elements (controlling chemical reactivity), 2) regioselective control elements (controlling the orientation of reactants) and 3) stereoselective control elements (controlling the spatial arrangement of atoms within the molecule), which may control either the relative (diastereoselective) or the absolute spatial arrangement (enantioselective control elements). 

Enantioselectivity control in a [2 + 2]-photocydoaddition reaction was achieved in a chiral, self-assembled host. Fluoranthenes and N-cyclohexylmaleimide underwent an intramolecular reaction in a cage made of M6L4, with the metal M being palladium (II) coordinated to a chiral diamine, and the ligand Lbeing2,4,6-tris(4 -pyridyl)-l,3,5-triazine. Up to 50% ee was observed [117]. 

The reactions which have been reported are listed in Table 1 along with representative catalysts. In the presence of the appropriate ligand and under suitable conditions, many of the reactions proceed with a surprising chemoselectivity, regioselectivity, and enantioselectivity. The main side reactions are the isomerization of the primary hydrovinylation product or its further reaction with a second molecule of ethylene and the oligomerization or polymerization of the individual alkenes. These side reactions frequently become of significance only after the consumption of one of the reacting alkenes or at elevated temperatures. The hydrovinylation products are presented briefly below and this is followed by a more detailed discussion of the enantioselective control. 

All the iPPs produced with this class of complexes had 4/w/4/n around 2, which is consistent with the single-site behavior. The NMR analysis of the iPP revealed equal amounts of mmmr and mmrr pentads, consistent with a mechanism of enantioselectivity controlled by the site chirality.276 To explain the increased isotacticity at increasing propylene pressure, it has been proposed that monomer insertion competes with chain epimerization. At increased propylene pressure, chain-epimerization reactions would be depressed by faster monomer insertion.247,248,276... 

The thiourea functionality, inserted on the most frequently used chiral pyrrolidine scalTold, works excellently as reactivity and enantioselectivity control co-factor by chelating the nitro group of the acceptor. This solution, adopted in 25, provides a family of robust catalysts that afford high yields (up to 98%) and great stereoselectivities (up to 99 1 dr and 99% ee) in direct Michael additions of ketones to various nitroolefins in water. ... 

Zhou explored the asymmetric hydrogenation of 2,3 disubstituted quinolines. They thought that the hydrogenation mechanism of 2,3 disubstituted quinolines was somewhat different from that of 2 substituted quinolines (Scheme 10.20) [3]. For the hydrogenation of 2 substituted quinoline, the hydrogenation of C=N bond is the enantioselectivity controlled step (Scheme 10.19, H-I), while the enantioselectivity controlled step of 2,3 disubstituted quinolines is the isomerization of enamine to imine and the hydrogenation of C=N bond, which is in fact a dynamic kinetic... 

Synthetic work in this most complex group is so far entirely due to Magnus and collaborators. Their very first essay in the area of aspidosper-mine alkaloid synthesis culminated in a brilliant synthesis of kopsan-5,22-dione (236) and kopsan-22-one (235) (370). Although performed without enantioselective control, this synthesis nevertheless established the Magnus strategy and laid the foundation for later, more refined syntheses. The sjmthesis involved the construction of a tetracycle 648 by the Diels-Alder... 

The rearrangement of ester enolates (Ireland rearrangement)36 41 87,88-91-257,292 467-469 derived from allyl esters is perhaps the most flexible Claisen variation, allowing the diasiereo-and enantioselective controlled synthesis of y.fS-unsaturated acids either by a change of the double-bond configuration of the allylic alcohol moiety or variation of the solvent system. 

Chiral molecules on the surface of the metal colloid can induce enantioselective control. Following this concept a new type of enantioselective platinum sol catalyst stabilized by the alkaloid dihydrocinchonidine was designed [120, 121]. Chirally modified Pt catalyst precursors have been prepared in different particle sizes by the reduction of platinum tetrachloride with formic acid in the presence of different amounts of the chiral alkaloid. Optical yields up to 80% ee were obtained in the hydrogenation of ethyl pyruvate. This type of catalyst was demonstrated to be structure insensitive since turnover frequencies (ca. 1 s ) and enantiomeric excess are independent of the particle size. 

Asymmetric addition of an oxindole enolate to nitroalkenes has been observed by Matsunaga, Shibasaki, and coworkers [25]. As illustrated in Scheme 9, chiral oxindole 35 was prepared with good diastereoselective and enantioselective control (30 1 dr, 97% ee) upon treatment of oxindole 32 with nitroalkene 33 in the presence of the bimetallic (Mn2) Schiff Base complex 34. Control experiments with various heterobimetallic complexes (Cu/Mn or Pd/Mn with organic catalyst 34) and a mononuclear complex of Mn with organic catalyst 34 led to decreased selectivity, highlighting the importance of the homodinuclear Mn2-34 complex for promoting the stereoselective transformation. 

Suedee, R. Srichana, T. Martin, G.P. Evaluation of matrices containing molecularly imprinted pol5mers in the enantioselective-controlled delivery of beta-blockers. J Control Release 2000, 66 (2-3), 135-147. 

Suedee, R., Bodhibukkana, C., Tangthong, N., Amnuaikit, C., Kaewnopparat, S., Srichana, T. (2008]. Development of a reservoir-type transdermal enantioselective-controlled delivery system for racemic propranolol using a molecularly imprinted polymer composite membrane, /. Control. Release. 129,170-178. 

The syntheses of cyclohexane derivatives by 6-exo-cyclizations of 2-halo-1,7-octadienes and l-halo-l,6-heptadienes are well documented, yet the formation of seven-membered rings during these cyclizations has also been observed (Scheme 10). This type of ring closure to cyclohexane derivatives has been applied in various total syntheses of natural products and been further elaborated applying chiral ligands in the catalysts to enable an enantioselective control (Tables 8 and 9). 

In 1996, Katsuki and co-workers studied asymmetric benzylic oxidation reactions by using Mn(salen) complexes. However, the best result they obtained was just 29% yield and 64% ee when 1,1-dimethylindane was used as the substrate and C25 as catalyst (Scheme 1.60). Later, they further enhanced the enantioselective control to 90% ee by changing the catalyst to C26, albeit the yield is only 24.5%. ... 

As a further extension, the You group reported a highly efficient synthesis of planar chiral ferrocenes via Pd-catalyzed annulation reactions of diary-lethynes (Scheme 5.11). The commercially available Af-Boc-L-Val-OH proved to be an efficient ligand with air as the sole oxidant. Ferrocenes with planar chirality could be synthesized with excellent enantioselectivity and moderate yields. A more sterically demanding P,N-ligand was easily prepared and showed enhanced enantioselective control in Pd-catalyzed allylic substitution reactions. 

Another example of organocatalytic AFC alkylation reaction with p,y-unsaturated a-keto esters was reported by Wang and co-workers in 2012. In the presence of 10 mol% rosin-derived tertiary amine-thiourea 96, a variety of p,y-unsaturated a-keto esters reacted with 1-naphthol smoothly to afford the modified chromanes 97 in good yields (79-86%) with up to 96% ee (Scheme 6.39). Again, the hydrogen bonding between substrates and catalyst was proposed to be a key element for the enantioselective control. 

The Chi group disclosed the first oxidative y-addition of enals to trifluo-romethyl ketones and enantioselective control via Lewis acid/NHC cooperative catalysis to give unsaturated 5-lactones. Enantioselective control involving the relatively remote enal y-carbon was achieved via Lewis acid and NHC cooperative catalysis (up to 81% yield and 94% ee). A reaction pathway... 

Besides the metal complexes based on Ni and Pd that were previously proved suitable for the asymmetric hydrovinylation reactions, Ru and Co complexes have also been employed in this type of transformation. The one sole example of Ru-catalyzed enantioselective hydrovinylation was reported by the List group in 2012. In their initial studies, they envisioned that Ni complexes with chiral counteranions might enable the desired reaction. However, it was found that these species either were unreactive or did not furnish enantioselective control in the hydrovinylation reactions. In this context, Jiang and List focused their attention on Ru catalysis (Table 9.6). Systematic evaluation on the effects of Ru complexes ligated by different phosphine ligands as well as various chiral phosphate anions introduced by the corresponding silver salts demonstrated that the combination of Ru complex Ru-3 and additive Ag-1 was the optimal catalyst, leading to acceptable results (entry 8). 

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