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With (R)-7-bis(m-xylyl)phosphino-7-bis(3,5-dimethylphenyl)phosphinyl-1,1'-spirobiindane; N-ethyl-N,N-diisopropylamine; bis(dibenzylideneacetone)-palladium(0); 4-nitro-benzoic acid; In ethylene glycol; at 80℃; for 7h;Inert atmosphere; Glovebox; |
B. Isolation of Heck productsGeneral procedure for asymmetric Heck reactions of 2,3-dihydrofuran: In an argon-filled glove box, Pd(dba)2 (7.2 mg, 0013 mmol) and (R)-Xyl-SDP(O) (10.8 mg, 0.015 mmol) were stirred in degassed ethylene glycol (1.0 mL)for 10-20 mm ma 10-mL reaction tube, followed by the addition of aryl bromide (0.50 mmol), N-diisopropylethylamine (255 pL, 1.5 mmol, 3 equiv), p-nitrobenzoic acid (83.6 mg, 0.5 mmol, 1 equiv) and 2,3-dihydrofuran (75 pL, 1.0 mmol, 2equiv). The mixture was vigorously stirred in a preheated oil bath at 80 C, until aryl bromide was fully consumed (monitored by GC). The reaction mixture was cooled to room temperature and subjected to flash chromatography (pentane/Et20) to give the purified product. The olefinic selectivity, or s selectivity, of the desired Heck isomer versus other isomers combined in the crude mixture was determined by GC. The enantioselectivity, (ee) of the purified product wasdetermined by chiral HPLC analysis using Daicel Chiralcel columns. The racemic Heck products were prepared by using racemic Xyl-SDP(O) ligand.Heck reaction of ArCI: Pd(dba)2 (14.4 mg, 0.025 mmol), (R)-Xyl-SDP(O) (21 .6 mg, 0.030 mmol), ethylene glycol (1.0 mL), 1-chloro-4-fluorobenzene (65.3 mg, 0.50 mmol), N-diisopropylethylamine (255 pL, 1.5 mmol), p-nitrobenzoic acid (83.6 mg, 0.5 mmol) and 2,3- dihydrofuran (150 pL, 2.0 mmol) were used. The reaction was complete in 45 h at 80C. The product was isolated by flash chromatography (10:1 to 5:1 pentane/Et20) as a colorless liquid. Yield: 62 mg, 75%. Olefinic selectivity in the crude product: 7:1.ee: 94%. Daicel Chiralcel OJ-H, 99:1 n-hexane/isopropanol, flow rate = 0.5 mL/min.1H NMR (400 MHz, CDCI3): 67.29-7.24 (m, 2H), 7.04-6.99 (m, 2H), 6.05-6.02 (m, 1H), 5.86-5.83 (m, IH), 5.77-5.74 (m, 1H), 4.87-4.82 (m, 1H), 4.77-4.72 (m, 1H). |