Chiral synthesis via organoboranes. 33. The controlled reaction of B-alkyldiisopinocampheylboranes with aldehydes providing a convenient procedure for the enantiomeric enrichment of the boronic ester products through kinetic resolution

Abstract

Enolization of Thioesters by ChxzBC1/Et3N. A representative example of enolization of S-tert-butyl thioacetate is described as follows. To a stirred solution of ChxzBCl (1.2 mL, 5.5 "01) and EbN (0.77 mL, 5.5 "01) in CCl, (15 mL) cooled at 0 "C was added an internal standard, benzene (0.5 mmol), followed by the slow addition of S-tert-butyl thioacetate (0.78 mL, 5 mmol). The molarity of the solution was adjusted to 0.3 M. The reaction mixture was stirred for 1 h and worked up as described for ketones. Analysis of the olefinic proton by 'H NMR suggests >95% enolization.Enolization of &Keto Ester by ChxzBC1/Et3N. The enolization of ethyl acetoacetate is described as follows. To a stirred solution of ChxzBC1 (1.2 mL, 5.5 mmol) and EbN (0.77 mL, 5.5 mmol) in CC14 (15 mL) cooled at 0 "C was added an internal standard, benzene (0.5 mmol), followed by the slow addition of ethyl acetoacetate (0.64 mL, 5 m o l ) . The molarity of the solution was adjusted to 0.3 M. The reaction mixture was stirred for 1 h and worked up as described previously for ketones. Analysis by 'H NMR showed 94% enolization.General Procedure for the Aldolization with Benzaldehyde. To a solution of enolborinate in diethyl ether generated from 5 mmol of the carbonyl compound using ChxzBC1/EbN as described above was added benzaldehyde (0.51 mL, 5 mmol) dropwise at -78 "C, and the mixture was stirred for 2-3 h. Then the reaction mixture was allowed to warm up overnight slowly to attain the room temperature. (Later we discovered that the reaction is essentially complete in 2-3 h at -78 "C, so that the slow warmup to 25 O C is unneccessary. Both procedures give the same results.) Then 10 mL of methanol was added to dissolve the precipitate (EhNHCl), 1.7 mL of HzOZ (30%) was added at 0 "C, and the mixture was stirred for 5-6 h at 25 "C. The solvent was then removed by water aspirator and the reaction mixture was extracted with ether, washed with dilute HC1 and water, and dried over anhyd Na2S04. The solvent was removed and the 1992,57, 504-511 products were analyzed as such by lH NMR to determine the syn/anti ratio.In the case of carboxylic acids, after the aldolization, 5 mL of H,O waa added to the reaction mixture at 25 "C. and the reaulth &e was stirred for 30 min. The products were then extra& with aqueous NaHC03, neutralized with 20% HC1, extracted with ether, dried over anhyd NazS04, concentrated, and analyzed by 'H NMR. Acknowledgment. We gratefully acknowledge financial support from the United States Office of Naval Research, which made this research possible.Registry No.

Chiral Synthesis via Organoboranes. 47. Efficient Synthesis of Unsymmetrical Ketones and Enantiomerically Pure Spiroketals Using (±)-Isopinocampheyldichloroborane

“…The elimination of α-pinene from trialkylboranes of the type 15 to give dialkylborinates 16 has earlier been studied with various aldehydes . For the present study, we chose isobutyraldehyde since (i) it reacts faster than other aldehydes such as acetaldehyde, (ii) it would ultimately lead to isobutanol which could be readily separated from the products either by distillation or by washing with water, and (iii) it provided a slightly more hindered borinate as compared to that with acetaldehyde or benzaldehyde.…”

Effizienz in der nichtenzymatischen kinetischen Racematspaltung

“…Zusammenfassend folgt an dieser Stelle nur ein kurzer Überblick über relevante Literaturstellen zu diversen Verbindungsklassen, die in kinetischen Racematspaltungen eingesetzt wurden: Aldehyde (Horner‐Emmons‐Olefinierung,60 Hydroacylierungen107), Allylalkohole (Sharpless‐Epoxidierung),13, 55 allylische Carboxylate (Pd‐katalysierte Substitutionen),36–38 Allylether (Carbometallierungen),58 Alkene (Osmylierungen),48, 49 Atropisomere,35 Azlacton‐Spaltung,14–16 1,3‐Dioxolan‐2,4‐dion‐Spaltung,17 Enone (Hydrierungen,22 Cuprat‐Additionen23e), Grignard‐Reagentien,24a–f, 25 Halogenide (Palladium‐katalysierte Amin‐Kupplungen),113 Ketone (Aldolreaktionen,23a Baeyer‐Villiger‐Oxidation,53 Horner‐Emmons‐Olefinierung,23b Enolisierungen,23c Organozink‐Additionen,23d Reduktionen,23f, 50, 51 Noyori‐Hydrierung18–21), Lactone,28e Organolithium‐Reagentien,28, 29 Phosphor‐33, 34b–e und Schwefelverbindungen 34a,c…”

Asymmetric Propargylation of Ketones Using Allenylboronates Catalyzed by Chiral Biphenols

“…The successful addition reaction in high enantioselectivities would be the result of a chiral boronate kinetic resolution process. 14 …”