Epoxide chiral benzylic

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

Solladie-Cavallo s group used Eliel s oxathiane 1 (derived from pulegone) in asymmetric epoxidation (Scheme 1.3) [1]. This sulfide was initially benzylated to form a single diastereomer of the sulfonium salt 2. Epoxidation was then carried out at low temperature with the aid of sodium hydride to furnish diaryl epoxides 3 with high enantioselectivities, and with recovery of the chiral sulfide 1. 

Several recent articles describe the ring-opening of chiral epoxides under microwave irradiation conditions (see also Scheme 6.103). In the context of the preparation of novel /32-adrenoceptor agonists related to formoterol and salmeterol, Fairhurst and a team from Novartis have described the synthesis of chiral ethanolamines by solvent-free microwave-assisted ring-opening of a suitable chiral epoxide precursor with secondary benzylated amines (Scheme 6.129) [262]. At 110 °C, the reaction occurred... 

A much more elaborate synthesis of 4-aryl-2-(benzyloxy)carbonyl-3-hydroxy tetrahydrofurans 88 from aryl epoxides requires the use of benzyl diazoacetate. This methodology can now be extended to a highly stereoselective synthesis of chiral tetrahydrofurans starting from optically active epoxides. The mechanism is believed to involve a Williamson-type cyclization as illustrated below <00TL8059>. 

A new C3-symmetric chiral phase-transfer catalyst that offers multipoint inteaction with a nucleophile has been described (Scheme 7.6) [23]. Thus, various quaternary ammonium salts were prepared through the ring opening of optically active epoxides, followed by quaternization of the resulting amines. Asymmetric benzylation of Schiff s base 20 in the presence of catalyst 24—26 yielded (S)-21 with moderate enantioselectivity. As expected, the C3-symmetric catalyst R,R,R)-26a provided... 

The enantio-determining step of nucleophilic additions to a-bromo-a,y -unsaturated ketones is mechanistically similar to those of nucleophilic epoxidations of enones, and asymmetry has also been induced in these processes using chiral phase-transfer catalysts [20]. The addition of the enolate of benzyl a-cyanoacetate to the enone 31, catalysed by the chiral ammonium salt 32, was highly diastereoselective and gave the cyclopropane 33 in 83% ee (Scheme 12). Good enantiomeric excesses have also been observed in reactions involving the anions of nitromethane and an a-cyanosulfone [20]. 

To a solution of chiral sulfide catalyst (9.5 mg, 0.05 mmol) and catechol (1 mg, 1 pmol) in t-BuOH (450 pL) was added the benzaldehyde (26 pL, 0.25 mmol), benzyl bromide (60 pL, 0.5 mmol) and n-Bu4NI (92 mg, 0.25 mmol). The resulting mixture was vigorously stirred at r.t. for 15 min (20-24 °C), and an aqueous solution of NaOH 28.5% (52 pL, 0.5 mmol, giving a 90 10 ratio of -BuOH water) was subsequently added. After 24 h of reaction, water (6 mL) was added, the two phases were separated, and the aqueous layer was extracted with diethyl ether (2x5 mL). The combined organic layers were dried over MgSC>4 and concentrated in vacuo. Purification by silica gel column chromatography afforded the two diastereoisomeric epoxides. 

A sequence of allylation, epoxidation and an acid-mediated 6-exo cyclisation converts salicylaldehydes into 2-hydroxymethyl-2-methyl-27/-[l]benzopyrans. A bicyclic chroman arising from attack of the hydroxymethyl group on the intermediate benzylic cation has been isolated <02SL322>. A twelve-step enantioselective synthesis of a 2-hydroxymethyl-2-methylchroman with an overall yield of 48% uses related methodology and introduces the chirality through an asymmetric Sharpless epoxidation <02JCS(P1)496>. 

The successful example of catalytic asymmetric chiral sulfonium epoxidation was reported with enantiomeric excess (43%) of trans-stilbene oxide (3.71) by the reaction of 4-chlorobenzaldehyde with benzyl bromide in acetonitrile at room temperature by using 0.5 equiv. of optically active sulfide 3.70 (with exo-OH group). Powdered KOH was used as a base. f... 

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