Indene, asymmetric epoxidation with

A typical manganese-salen complex (27)[89] is capable of catalysing the asymmetric epoxidation of (Z)-alkenes (Scheme 18) using sodium hypochlorite (NaOCl) as the principle oxidant. Cyclic alkenes and a, (3-unsaturated esters are also excellent starting materials for example indene may be transformed into the corresponding epoxide (28) with good enantiomeric excess1901. The epoxidation of such alkenes can be improved by the addition of ammonium acetate to the catalyst system 911. 

In 2002, Bulman Page etal. reported the dibenzazepinium salt analogs of catalysts 64e and 641,65 and 66, respectively. These were examined in the asymmetric epoxidation reactions of phenylcyclohexene, phenyldihydronaphthalene, and indene, with very similar results being observed with 65 and 66 as with 64e and 641 (Figure 15) <2002SL580>. 

Preparation. A number of methods have been reported for both the racemic and asymmetric preparations of l-amino-2,3-dihydro-lH-inden-2-ol (1), most commonly starting from inexpensive and readily available indene. These methods have been described in detail in recent reviews. The valuable properties of 1 as both a component of a medicinally active compound and as a chirality control element, derive primarily from its rigid and well-defined stereochemical structure. As a result, the compound is most desirable in enantiomerically pure form. One of the most efficient asymmetric syntheses of 1, which may be employed for the synthesis of either enantiomer of the target molecule, involves an asymmetric epoxidation (89% yield, 88% ee) of indene to give epoxide 2 using the well-established Jacobsen catalyst. This is followed by a Ritter reaction using oleum in acetonitrile resulting in conversion to the oxazoline (3) which is subsequently hydrolysed to the amino alcohol. Fractional crystallization with a homochiral diacid permits purification to >99% ee (eq 1). ... 

Complete conversions and good enantiomeric excesses (64-100%) were achieved in the asymmetric epoxidation of chromenes and indene using UHP as oxidant and a novel dimeric homochiral Mn(III) Schiff base as catalyst. The reactions were carried out in the presence of carboxylate salts and nitrogen and oxygen coordinating co-catalysts. However, the epoxidation of styrene unfortunately proceeded with incomplete conversion and only 23% ee. Modification of the catalyst and use of pyridine 7V-oxide as cocatalyst allowed improvement of the ee to 61% (Scheme 18). ... 

Catalytic oxidahon reachons were among the earliest explored applicahons of the FBS concept because of the chemical and thermal stabihty of perfluorocarbons, the convenient partihon of the final polar products into the organic phase, and the possible increased lifetime of the catalysts confined in the fluorous phase [4—6]. The first example of enantioselechve catalysis under FBS condihons, reported in 1998, also dealt with an oxidation process, namely the epoxidahon of prochiral alkenes [26]. Mn(III)-complexes of salen hgands 2 and 3 were found to catalyze the asymmetric epoxidation of indene in a two-phase system CH2Cl2/perfluoroc-tane at 20 °C under an atmospheric pressure of oxygen in the presence of pivalal-dehyde (Scheme 5.1). 

It is well known that BLM oxidizes not only double-stranded DNA but also various olefinic substrates. Hitherto reported are oxidation of stilbene, styrene, chalcone, cinnamic acid, cyclohexene, norbornene, and indene using Fe(II), Fe(III), Cu(II), Mn(III), or Zn(III) complexes of BLM in the presence of O2, CgHsIO, or KHSO2 as oxygen donor [7, 8]. We reported that stilbene can be epoxidized with Fe(III)-H202 complex system of PYMLs [59]. Although the formation of chiral iron chelate was reasonably proposed as shown in Fig. 2, there has been no report on asymmetric induction in the oxidation mediated by BLM-metal complex systems. We found that cis-P-methylstyrene is affected by the chiral environment of the iron center of BLM and PYML. 

The asymmetric oxidation of indene to the corresponding epoxide (Equation 24) is carried out commercially by Sepracor on a small scale. Chiral indene oxide is an intermediate in the synthesis of crixivan (an HIV protease inhibitor). Reaction is carried out at 5°C with moderately high turnover numbers in the presence of an exotic donor ligand ( P3NO , 3-phenylpropylpyridine N oxide) and sodium hypochlorite as the terminal oxidant. A similar epoxidation of a simple cis olefin (Equation 25) leads to an enantiomerically pure amino-alcohol used in the synthesis of taxol, a potent anticancer drug. 

Due to the demand for inexpensive anti-HIV agents, several reactions for the synthesis of Indinavir (70, an HIV protease inhibitor of Merck Co.) have been reported. Enantioselective epoxidation of simple alkenes with bleach is achievable in the presence of the Mn " complex 69 possessing a well-designed chiral salen ancillary [69]. Scheme 20 exemplifies its application to the synthesis of Indinavir (70), by way of indene oxide (68) in 88 % ee [69]. This method is also useful for the asymmetric synthesis of a chromene epoxide in 97 % ee serving as an intermediate for Lemakalim, a K" -channel opening agent [70]. 

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