50% ethyl glyoxylate oligomer in toluene (Fluka, 88.6g) was distilled at atmospheric pressure using a short (2in) Vigreaux column and oil bath temperature 130-185C (gradually increased over 30 min period) untill only a small residue remained. First few mL were discarded, and then the entire volume collected. The obtained yellowish distillate containing toluene-ethyl glyoxylate mixture was immediately re-distilled at 30Torr. After toluene freaction, pure ethyl glyoxylate distilled at 48-50C/30Torr. Y=25.88g of a pale yellow mobile liquid (58.5%th). 1H-NMR indicated only a trace of toluene (<3%) in this product. The density of pure Et-glyoxylate is 1.051g/mL at 23C. 1H-NMR(CDCl3): 9.31(s, 1H), 4.23(q, 7Hz, 2H), 1.31(t, 7Hz, 3H)
The glyoxylate oligomerizes readily on contact with metal impurities, activated 4A mol sieves, teflon surfaces. It reacts with moisture to form hydrate. It can be handled briefly (20 min) at room temperature and stored on dry ice bath under Ar for few hours without oligomerization. Unused material can be kept in freezer and depolymerized by distillation at atmospheric pressure just before use.
The vacuum re-distillation was done in order to break the glyoxylate azeotrope with toluene. (Neat glyoxylate was needed for solvent and reaction stoechiometry studies.) It was later found that the presence of toluene was not detrimental to yield or ee. For preparative experiments, the vacuum re-distillation of glyoxylate was unnecessary – the mix of glyoxylate with toluene (55-75% glyoxylate) obtained from the commercial oligomer solution by simple distillation at atmospheric pressure could be used directly. Since ethyl glyoxylate is used in excess (3.5 to 5 eq.) and the glyoxylate excess improves the yield and shortens the reaction time, using approximate quantity of toluene solution is acceptable for preparative purposes.
Alpha methyl styrene 0.330mL (2.50 mmol) and neat ethyl glyoxylate 1.07mL (12.5mmol) was added to a stirred slurry of [Cu(S-tBuBox)(H2O)2](SbF6)2 4.3mg (0.2mol%) in a 2:1 mixture TBME/chlorobenzene (3 mL) at -20C. After a complete catalyst dissolution, the reaction mixture was kept in a sealed flask in a freezer (-20C) for 36 hours. The reaction mixture was poured onto a column of silica in 1:3 mix ether-hexane and eluted with the same mixture. Y=494mg (90%) of a colorless oil 98.6% ee (chiral GC, cyclodexB column) [alpha]D23 +1.77(benzene, c=6.215), 1H(CDCl3, 400MHz): 7.43(d, 7Hz, 2H), 7.31(m, 4H), 5.40(s, 1H), 5.22(s, 1H), 4.28(dd, 8Hz, 5Hz, 1H), 4.06(m, 2H), 3.07(dd, 14Hz, 5Hz, 1H), 3.01(br s, 1H), 2.86(dd, 14Hz, 8Hz, 1H), 1.22(t, 7Hz, 3H) 13C(CDCl3, 100MHz):174.34, 143.49, 140.22, 128.15, 127.62, 126.29, 116.02, 69.05, 61.39, 40.35, 13.96
With 1 mol% of the catalyst and 3.5 eq. of ethyl glyoxylate, 1 mmol of alpha methyl styrene in 3mL of TBME/chlorobenzene (2:1) at -20C/24h gave 90%Y, 99.0% ee.
A mixture of 75% ethyl glyoxylate solution in toluene (prepared by atmospheric-pressure distillation of the commercial solution) 1.25mL (9 mmol) and methylene cyclohexane 0.303mL (2.50 mmol) was cooled on ice bath. [Cu(S-tBuBox)(H2O)2](SbF6)2 4.3mg (0.2mol%) solid was added and the mixture was stirred at 0C for 25 hours. The reaction mix was poured onto a column of silica in 1:3 mix ether-hexane and eluted with the same mixture. Y=428mg of a colorless oil (87% th), 97.9% ee (chiral GC, cyclodexB) [alpha]D23 -5.67 (benzene, c=5.15) 1H(CDCl3, 400MHz): 5.48(br s, 1H), 4.23(dd, 8Hz, 5Hz, 1H), 4.19(q, 6Hz, 2H), 2.85(br s, 1H), 2.39(dd, 14Hz, 5Hz, 1H), 2.24(dd, 14Hz, 8Hz, 1H0, 1.98-1.88(br m, 4H), 1.51-1.48(br m, 4H), 1.25(t, 6Hz, 3H), 13C(CDCl3, 100MHz): 174.86, 132.86, 125.19, 69.12, 61.32, 43.13, 28.26, 25.15, 22.05, 14.08
With 1mol% of the catalyst and 5 eq. of ethyl glyoxylate, 0.5 mmol of methylenecyclohexane in 1.5mL of 2:1 mix TBME/chlorobenzene at -20C/24h gave 99% Y in 98.9% ee