Alkene oxidation enantioselectivity

A detailed investigation showed that PhB(OH)2 does not interfere with the chiral ligand, leaving the enantioselective step of alkene oxidation intact. Its main role-apart from protecting the diol products against potential over-oxidation - is to remove the diol via an electrophilic cleavage, which is in contrast to the conventional hydrolytic cleavage of the AD protocols.126... 

In Lemaire s work, BINOL was used in place of resorcinol to prepare chiral bis(diarylalkylphosphite) end groups on poly(ethylene glycol). When this ligand 141 was combined with [Rh(cod)2]Bp4, a catalyst was obtained that exhibited thermoregulated behavior similar to that seen by Jin with other poly(alkene oxide)-boimd Rh catalysts. However, while high conversions in hydroformyla-tion were observed, the enantioselectivity for the hydroformylation of styrene by the Rh complex of this phosphite 141 was only modest (ca. 25% e.e.). 

Toribatake K, Nishiyama H. Asymmetric diboration of terminal alkenes with a rhodium catalyst and subsequent oxidation enantioselective synthesis of opticaUy active 1,2-diols. Angetv Chem Int Ed Engl. 2013 52 11011-11015. 

Asymmetric Hydroboration. Hydroboration—oxidation of (Z)-2-butene with diisopinocampheylborane was the first highly enantioselective asymmetric synthesis (496) the product was R(—)2-butanol in 87% ee. Since then several asymmetric hydroborating agents have been developed. Enantioselectivity in the hydroboration of significant classes of prochiral alkenes with representative asymmetric hydroborating agents is shown in Table 3. 

The first, and so far only, metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction of nitrile oxides with alkenes was reported by Ukaji et al. [76, 77]. Upon treatment of allyl alcohol 45 with diethylzinc and (l ,J )-diisopropyltartrate, followed by the addition of diethylzinc and substituted hydroximoyl chlorides 46, the isoxazolidines 47 are formed with impressive enantioselectivities of up to 96% ee (Scheme 6.33) [76]. 

Accordingly, cyclic nitronates can be a useful synthetic equivalent of functionalized nitrile oxides, while reaction examples are quite limited. Thus, 2-isoxazoline N-oxide and 5,6-dihydro-4H-l,2-oxazine N-oxide, as five- and six-membered cyclic nitronates, were generated in-situ by dehydroiodination of 3-iodo-l-nitropropane and 4-iodo-l-nitrobutane with triethylamine and trapped with monosubstituted alkenes to give 5-substituted 3-(2-hydroxyethyl)isoxazolines and 2-phenylperhydro-l,2-oxazino[2,3-fe]isoxazole, respectively (Scheme 7.26) [72b]. Upon treatment with a catalytic amount of trifluoroacetic acid, the perhydro-l,2-oxazino[2,3-fe]isoxazole was quantitatively converted into the corresponding 2-isoxazoline. Since a method for catalyzed enantioselective nitrone cycloadditions was established and cyclic nitronates should behave like cyclic nitrones in reactivity, there would be a good chance to attain catalyzed enantioselective formation of 2-isoxazolines via nitronate cycloadditions. 

The overall result of the sequence hydroboration -I- oxidation is a regioselective and-Markownikoff-addition of water to an alkene. This reaction is an important method in organic synthesis, since it can be made stereoselective and even enantioselective. 

Ordinary alkenes (without an allylic OH group) have been enantioselectively epoxidized with sodium hypochlorite (commercial bleach) and an optically active manganese-complex catalyst. Variations of this oxidation use a manganese-salen complex with various oxidizing agents, in what is called the Jacobsen-Katsuki... 

Other metals can also be used as a catalytic species. For example, Feringa and coworkers <96TET3521> have reported on the epoxidation of unfunctionalized alkenes using dinuclear nickel(II) catalysts (i.e., 16). These slightly distorted square planar complexes show activity in biphasic systems with either sodium hypochlorite or t-butyl hydroperoxide as a terminal oxidant. No enantioselectivity is observed under these conditions, supporting the idea that radical processes are operative. In the case of hypochlorite, Feringa proposed the intermediacy of hypochlorite radical as the active species, which is generated in a catalytic cycle (Scheme 1). 

Compounds lb and 2b were the Urst fluorinated ligands tested in Mn-catalyzed alkene epoxidation [5,6]. The biphasic Uquid system perfluorooc-tane/dichloromethane led to excellent activity and enantioselectivity (90% ee) in the epoxidation of indene with oxygen and pivalaldehyde (Scheme 1, Table 1). In addition, the fluorous solution of the catalyst was reused once and showed the same activity and selectivity. This represents a considerable improvement over the behavior in the homogeneous phase, where the used catalyst was bleached and reuse was impossible. Unfortunately, indene was the only suitable substrate for this system, which failed to epoxidize other alkenes (such as styrene or 1,2-dihydronaphthalene) with high enantioselectivity. The system was also strongly dependent on the oxidant and only 71% ee was obtained in the epoxidation of indene with mCPBA at - 50 °C. 

Very few examples have been described for the non-covalent immobilization of chiral porphyrin complexes (Fig. 26). In the first case, the porphyrin-dichlororutheninm complex was encapsulated in silica, which was prepared around the complex by a sol-gel method [78], in an attempt to prevent deactivation observed in solution in the epoxidation of different alkenes with 2,6-dichloropyridine N-oxide. In fact, the heterogeneous catalyst is much more active, with TON up to 10 800 in the case of styrene compared to a maximum of 2190 in solution. Enantioselectivities were about the same imder both sets of conditions, with values aroimd 70% ee. 

The asymmetric nickel-catalyzed hydroalumination of prochiral terminal alkenes using adducts of BujAl and chiral amines was reported in 1981 [74], Among the different amines investigated, (-)-N,N-dimethylmenthylamine (DMMA) gave the best enantioselectivities. For example, reaction of 2,3,3-trimethyl-l-butene (39) at room temperature with 0.33 equiv. of the DMMA/iBu3Al adduct in the presence of 0.6 mol% of Ni(mesal)2 gave, after oxidation of the intermediate organoaluminum compounds, 2,3,3-trimethyl-l-butanol 40 in 76% yield and 27% ee (Scheme 2-19). 

Finally, with the aim of discovering novel chiral oxomolybdenum catalysts able to perform enantioselective alkene epoxidations, Kuhn et al. have reported the exploration of the catalytic behaviour of a series of dioxomolybdenum(VI) complexes with chiral cw-8-phenylthiomenthol ligands derived from ( + )-pulegone. Therefore, the epoxidation of c -p-methylstyrene using t-butyl-hydroperoxide as the oxidant and performed in the presence of ( + )-(2i ,5i )-2-[1-methyl-l-(phenylthio)ethyl]-5-methylcyclohexanone oxime as the ligand, did not produce, however, a significant optical induction in these conditions. 

Scheme 12.10 gives some examples of these oxidations. Entry 1 is one of several aryl-conjugated alkenes that were successfully epoxidized. Entry 2 is a reaction that was applied to enantioselective synthesis of the taxol side chain. Entry 3 demonstrates... 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

Attempts have been made to exploit the intrinsic C2 symmetry of the phenolate-based dinickel core in enantioselective catalytic reactions. Therefore, enantiomerically pure C2-symmetric ligands such as (736a) and the corresponding dinickel systems (736b) have been prepared ( Equation (27)),1890 and (736b) was tested in the epoxidation of unfunctionalized alkenes with sodium hypochlorite as the oxidant. The catalytic reaction was found to be highly pH dependent with an optimum at a pH of 9. While the complex is catalytically active, significant enantioselectivity was not achieved. 

The Pd/MOP combination has proved active for the asymmetric hydrosilylation of cyclic alkenes and dienes. Thus treatment of norbornene with HSiCl3 at 0 °C for 24 h in the presence of 0.01 mol.% of M eO-MOIV[Pd(// -C3H5)Cl]2 gave quantitative yield of evo-2-(trichlorosilyl)norbornane oxidation produced the corresponding alcohol in 93% ee (Equation (12)). Lowering the temperature (to — 20 °C) increased this to a 96% ee. Both mono- and difunctionalization of nbd has proved possible, depending upon the quantity of trichlorosilane used (Scheme 22). In both reactions, extremely good enantioselectivities are observed 113... 

---