Stilbene, asymmetric dihydroxylation

The interest in asymmetric synthesis that began at the end of the 1970s did not ignore the dihydroxylation reaction. The stoichiometric osmylation had always been more reliable than the catalytic version, and it was clear that this should be the appropriate starting point. Criegee had shown that amines, pyridine in particular, accelerated the rate of the stoichiometric dihydroxylation, so it was understandable that the first attempt at nonenzymatic asymmetric dihydroxylation was to utilize a chiral, enantiomerically pure pyridine and determine if this induced asymmetry in the diol. This principle was verified by Sharpless (Scheme 7).20 The pyridine 25, derived from menthol, induced ee s of 3-18% in the dihydroxylation of /rcms-stilbene (23). Nonetheless, the ee s were too low and clearly had to be improved. 

Sharpless stoichiometric asymmetric dihydroxylation of alkenes (AD) was converted into a catalytic reaction several years later when it was combined with the procedure of Upjohn involving reoxidation of the metal catalyst with the use of N-oxides [24] (N-methylmorpholine N-oxide). Reported turnover numbers were in the order of 200 (but can be raised to 50,000) and the e.e. for /rara-stilbene exceeded 95% (after isolation 88%). When dihydriquinidine (vide infra) was used the opposite enantiomer was obtained, again showing that quinine and quinidine react like a pair of enantiomers, rather than diastereomers. 

Asymmetric dihydroxylation can be achieved using osmium tetroxide in conjunction with a chiral nitrogen ligand. " The very successful Sharpless procedure uses the natural cinchona alkaloids dihydroquinine (DHQ) and its diastereomer dihy-droquinidine (DHQD), as exemplified in the epoxidation of imni-stilbene... 

Other functionalized supports that are able to serve in the asymmetric dihydroxylation of alkenes were reported by the groups of Sharpless (catalyst 25) [88], Sal-vadori (catalyst 26) [89-91] and Cmdden (catalyst 27) (Scheme 4.13) [92]. Commonly, the oxidations were carried out using K3Fe(CN)g as secondary oxidant in acetone/water or tert-butyl alcohol/water as solvents. For reasons of comparison, the dihydroxylation of trons-stilbene is depicted in Scheme 4.13. The polymeric catalysts could be reused but had to be regenerated after each experiment by treatment with small amounts of osmium tetroxide. A systematic study on the role of the polymeric support and the influence of the alkoxy or aryloxy group in the C-9 position of the immobilized cinchona alkaloids was conducted by Salvadori and coworkers [89-91]. Co-polymerization of a dihydroquinidine phthalazine derivative with hydroxyethylmethacrylate and ethylene glycol dimethacrylate afforded a functionalized polymer (26) with better swelling properties in polar solvents and hence improved performance in the dihydroxylation process [90]. 

Catalytic asymmetric dihydroxylation (14, 237-239 15, 240-241). Complete details are now available for this reaction with a solid substrate, ftms-stilbene, in acetone/water (3 1, v/v) with dihydroquinidine 4-chlorobenzoate as catalyst.1 4... 

More recently, Petri et a/.[136] have copolymerized the chiral ligand (QHN)2-PHAL (Scheme 9.3) directly with ethylglycol dimethacrylate using AIBN as radical initiator. This material revealed high activities (68-80 % yield) and enantioselectivities (ee > 98 %) for asymmetric dihydroxylation of frans-stilbene using K3Fe(CN)6 as secondary oxidant. However, the authors noted that the catalytic material still contained unbound bis-alkaloid. 

The strategy is impressively simple the phthalazine derivative 15 can readily be prepared from quinine in one step. Being a divinyl derivative, it can be submitted as a cross-linking unit in the radical polymerization of methyl methacrylate (MMA) or 2-hydroxy methacrylate (HEMA). Thereby, an immobilized (DHQ-PHAL) derivative 16 is obtained, which is suited for the asymmetric dihydroxylation of frantr-stilbene (>99 % ee) and ( )-cinnamic acid methyl ester (>99 % ee. Table 1). The insoluble catalyst can be recovered by simple filtration, and its repeated... 

By employing polymer-bound alkaloid derivatives, heterogeneous catalytic asymmetric dihydroxylation has been achieved with good to excellent enantioselectivities in the dihydroxylation of trans-stilbene. These polymers can be recovered and reused while both the yields and the optical purities of diols were maintained. 

The present procedure describes a convenient preparation of threo-stilbene dioi on a 1-moie scaie and iliustrates the utiiity of the catalytic, asymmetric dihydroxylation (ADH) of solid substrates on a large scale. Note that this procedure... 

Another example of a chiral polymer that can be used in solution and recovered as a solid is the copolymer 73 [ 110]. This soluble block copolymer-supported ligand was very effective both in terms of synthetic yield and stereoselectivity in an asymmetric dihydroxylation of (E)-stilbene (Eq. 27) with an average synthetic yield of 84% and an average e.e. of 98% through five cycles. 

Scheme 5.12. Asymmetric dihydroxylation of tranj-stilbene using NAP-Mg-OsW.

Stilbene diols such as 3 are gaining prominence both as synthetic intermediates and as effective chiral auxiliaries. While the diols can be prepared in high by Sharpless dihydroxylation, it would be even more practical to prepare them by direct asymmetric pinacol coupling. N. N. Joshi of the National Chemical Laboratory in Pune reports (J. Org. Chem. 68 5668,2003) that 10 mol % of the inexpensive Ti salen complex 2 is sufficient to effect highly enantioselective and diastereoselective pinacol coupling of a variety of aromatic aldehydes. Most of the product diols are brought to >99% by a single recrystallization. 

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