Hexamethylphosphoramide (HMPA) was first stirred with calcium hydride for 24 h under nitrogen at room temperature. 88% ee determined by HPLC analysis. This paper was submitted directly (Track II) to the PNAS office. Common Conditions: OsO 4 + NaIO 4. The mild condition for the formation of the alkynylzinc reagent enables the use of functional alkynes in this asymmetric reaction with excellent enantioselectivity. The other is the “chiral amine” strategy, applying terminal alkynes, aldehydes, and chiral amines such as (S)- or (R)-α,α-diphenylprolinol or (S)- … It is a two step process where first the terminal alkyne is converted into enol and then tautomerization occurs to give corresponding aldehyde. 1,3-Diphenyl-prop-2-yn-1-ol. Then, an aldehyde (0.25 mmol) was added and the reaction was completed in 3–4 h. Saturated ammonium chloride solution was added to quench the reaction, and methylene chloride was used for extraction. Entries 14–16 also demonstrate that the addition of HMPA makes it possible to conduct the highly enantioselective reaction of benzaldehyde with functional alkynes. minor = 45.1 min. Carbonyl compounds are given as products. Alkynes hydration is much harder than alkene hydration. minor = 30.4 min. 53% yield. 1,5-Diphenyl-pent-1-en-4-yn-3-ol. 93% ee determined by HPLC analysis (2% i-PrOH in hexane at 1.0 ml/min). The high temperature of this step caused the decomposition of certain functional alkynes. Watch Queue Queue 88% ee determined by HPLC analysis. major = 40.0 min, and t Hydroboration of alkyne results in the formation of an aldehyde. E-mail: lp6n{at}virginia.edu. 1H NMR (300 MHz, CDCl3) δ 7.53–7.50 (m, 2H), 7.41–7.32 (m, 3H), 5.50 (br, 1H), 4.75 (d, J = 1.8 Hz, 2H), 2.21 (br, 1H), 2.09 (s, 3H). major = 13.6 min, and t Retention time: t Retention time: t Two general methods exist for the asymmetric synthesis of propargylic alcohols, including the asymmetric reduction of ynones (12–18) and the nucleophilic addition of metal acetylides to aldehydes (19–29). In the reaction catalyzed by BINOL/Ti(OiPr)4/Et2Zn, refluxing of a terminal alkyne and Et2Zn in toluene was required in the first step to prepare the corresponding alkynylzinc. Summary. After the mixture was stirred for 3 h, an aldehyde (0.25 mmol) was added and the stirring continued for 8 h. The reaction was quenched with ice and extracted with methylene chloride. 1-Pentafluorophenyl-3-phenyl-prop-2-yn-1-ol. 93% ee determined by HPLC analysis. Astronomers ostensibly know plenty about neutron stars. Addition Reactions of Alkynes. 4,4-Diethoxy-1-phenyl-but-2-yn-1-ol. We therefore tested the use of these compounds as additives for the (S)-BINOL-catalyzed reaction of phenylacetylene with benzaldehyde for the synthesis of the propargylic alcohol 2 (Scheme 2). Copyright © 2020 National Academy of Sciences. indeed gives only acetaldehyde. In particular, the method using BINOL/Ti(OiPr)4/Et2Zn is highly enantioselective for the reaction of terminal alkynes with a broad range of substrates, including alkyl, aryl, and α,β-unsaturated aldehydes (24, 25). Reactions of phenylacetylene with benzaldehyde in the presence of (, Asymmetric reactions of various alkynes with aromatic aldehydes in the presence of (, Proceedings of the National Academy of Sciences, Earth, Atmospheric, and Planetary Sciences, Opinion: The perils of biodiversity conservation during a global crisis, Inner Workings: The quest to understand neutron stars and matter at the extremes, Opinion: To stop the next pandemic, we need to unravel the origins of COVID-19, Copyright © 2004, The National Academy of Sciences. The racemic compound was prepared by replacing (S)-BINOL with racemic BINOL in the alkyne addition to benzaldehyde (37). 1-(4-Fluoro-phenyl)-3-phenyl-prop-2-yn-1-ol. This video is unavailable. Watch Queue Queue. Retention time: t 1H NMR (300 MHz, CDCl3) δ 7.48–7.45 (m, 2H), 7.41–7.39 (m, 2H), 7.33–7.26 (m, 4H), 7.15 (d, J = 7.5, 1H), 5.64 (br, 1H), 2.38 (s, 3H), 2.24 (br, 1H). Methylene chloride and tetrahydrofuran were dried by passing through an activated alumina column under nitrogen and were stored over 4-Å molecular sieves before use. Acetic acid 4-hydroxy-4-phenyl-but-2-ynyl ester. General Data. 1H NMR (300 MHz, CDCl3) δ 8.38 (d, J = 8.1 Hz, 1H), 7.93–7.84 (m, 3H), 7.60–7.44 (m, 5H), 7.33–7.28 (m, 3H), 6.50 (d, J = 5.1 Hz, 1H), 2.38 (d, J = 6.0 Hz, 1H). Common Conditions: OsO 4 + NaIO 4. minor = 35.6 min. explain why it is necessary to use a bulky, sterically hindered borane when preparing vinylic boranes from terminal alkynes. When phenylacetylene, Et2Zn, and HMPA were mixed in methylene chloride in the first step and (S)-BINOL and Ti(OiPr)4 were added later, the enantioselectivity was significantly reduced (entry 8). These substrates underwent decomposition when heated under reflux in toluene in the presence of Et2Zn. 1H NMR (300 MHz, CDCl3) δ 7.60 (s, 1H), 7.49–7.44 (m, 3H), 7.34–7.30 (m, 5H), 5.66 (d, J = 5.7 Hz, 1H), 2.32 (d, J = 6.0 Hz, 1H). 1H NMR (300 MHz, CDCl3) δ 7.44–7.41 (m, 2H), 7.33–7.30 (m, 3H), 5.96 (d, J = 7.8 Hz, 1H), 2.66 (d, J = 8.1, 1H) (34). major = 10.5 min, and t 77% yield. 93% ee determined by HPLC analysis. The use of excess NaIO4 serves to regenerate OsO4, allowing the use of only a catalytic amount of toxic OsO4. 1H NMR (300 MHz, CDCl3) δ 7.53–7.50 (m, 2H), 7.40–7.29 (m, 3H), 5.51 (br, 1H), 5.34 (d, J = 1.2 Hz, 1H), 3.79–3.68 (m, 2H), 3.64–3.53 (m, 2H), 2.23 (br, 1H), 1.221 (t, J = 6.9 Hz, 3H), 1.215 (t, J = 6.9 Hz, 3H) (36). Neural signatures of complex cognitive processing can occur in the absence of visual awareness, according to a case study of a person with distorted visual perception. 1H NMR (300 MHz, CDCl3) δ 7.53–7.43 (m, 6H), 7.34–7.29 (m, 3H), 5.64 (br, 1H), 2.27 (br, 1H) (29). 1H NMR spectra were obtained by using the Varian-300 MHz spectrometer. major = 11.9 min, and t 72% yield. 1H NMR (300 MHz, CDCl3) δ 7.63–7.60 (m, 2H), 7.48–7.28 (m, 8H), 5.69 (br, 1H), 2.26 (br, 1H) (21, 30). Diethylzinc (95%) was purchased from Strem (Newburyport, MA). The greater use of alkynylzincs is because alkynylzincs can be directly prepared in situ from the reaction of terminal alkynes with the commercially available alkylzincs or Zn(OTf)2. 3-Phenyl-1-o-tolyl-prop-2-yn-1-ol. predict the product formed when the vinylic borane produced from a terminal alkyne is treated with basic hydrogen peroxide. In this case, an aldehyde is formed. Thus, entry 22 is identified as the optimized procedure for this reaction because of its high enantioselectivity. Alkene to Aldehyde.