Scheme 1-26. Addition of Nitromethane to Ethyl (Z)-2-benzoyl-4-bromo-5-methylhex-2-enoate
We believe the cyclopropane is formed by a Michael addition of nitromethane to afford intermediate 1.92, followed by an intramolecular SN2-type displacement of the halogen. It is noteworthy that in the case of catalyst 1.19a, we obtain only 13% conversion; however, the recovered starting material is isolated in a different E:Z ratio than the starting material. This indicates to us that the substrate does indeed form the dienolate under reaction conditions. We hypothesized that the low conversion to the cyclopropane was due to the equivalent of HBr formed during the cyclization step.
71
This could quench the catalyst and shut down reactivity. Indeed, when we employed a full equivalent of DBU, we observed full conversion to the cyclopropane 1.91.
We realized the challenge in rendering this reaction catalytic and enantioselective would be finding a way to turn over the catalyst. Any additives to the reaction would need to prevent HBr from interfering with the active catalyst without catalyzing the Michael addition on its own via deprotonation of the nitroalkane. We tried adding weak amine bases as additives, including 2,6-lutidine (Table 1-11, entry 1) and pyridine (Table 1-11, entry 2), however, conversion remained low. We also tried additives that could potentially act as HBr scavengers, like 1-methyl-1-cyclohexene (Table 1-11, entry 3) and propylene oxide (Table 1-11, entry 4), but also failed to increase in conversion.
Table 1-11. Effect of Additives on Addition of Nitromethane to Ethyl (Z)-2-benzoyl-4-bromo-5- methylhex-2-enoate
entry additive conversion
1 2,6-lutidine 7%
2 pyridine 9%
3 1-methyl-1-cyclohexene 9%
4 propylene oxide 6%
We next became interested in employing a phase transfer catalyst under basic conditions for this transformation.92 It was our hope that formation of HBr in the cyclopropanation would not be detrimental in a phase transfer system. Initial attempts to catalyze the nitromethane addition with benzylated cinchonidine phase transfer catalyst 1.92, in the presence of either KOH or KF afforded only trace amounts of the desired cyclopropane (Table 1-12, entry 1-2). We were excited to see that by
72
switching the base to Cs2CO3, the conversion to cyclopropane increased 75% (Table 1-12, entry 3). Cyclopropane 1.91 was obtained in 11:1 dr, but unfortunately the product was nearly racemic. Table 1-12. Optimization of Phase Transfer Catalyzed Addition of Nitromethane
entry PTC base solvent conversion dr er
1 1.92 KF toluene trace - -
2 1.92 KOH toluene trace - -
3 1.92 Cs2CO3 toluene 75% 11:1 52:48 4 1.92 K2CO3 toluene 56% 8.8:1 56:44 5 1.92 Cs2CO3 DCM 100% 3.2:1 52:48 6 1.93 Cs2CO3 toluene 40% 10:1 53:47 7 1.93 Cs2CO3 DCM 70% 4.7:1 54:46 8 1.94 Cs2CO3 DCM 54% 7:1 51:49 9 1.95 Cs2CO3 DCM 75% 6.7:1 55:45
K2CO3 can also promote the reaction, but in diminished conversion and diastereoselectivity, with no appreciable increase in enantioselectivity (Table 1-12, entry 4). Switching the solvent to dichloromethane resulted in full conversion to cyclopropane, but a large drop in diastereoselectivity, and no enantioselectivity (Table 1-12, entry 5). We elected to run a limited catalyst screen to determine what aspects of the phase transfer catalyst could be changed to improve the reaction. By switching the benzyl group to contain a more electron poor 3,5-CF3 aryl group 1.93, we observed moderate conversion and excellent diastereoselectivity in toluene but, continued to struggle to achieve any
73
enantioinduction (Table 1-12, entry 6). Similar to our previous trial (entry 5), switching to DCM as solvent resulted in an increase in conversion and simultaneous decrease in diastereoselectivity (Table 1-12, entry 7). Neither quinine-derived catalyst 1.94 nor its O-protected analog provided an improvement to conversion or stereoselectivity (Table 1-12, entries 8-9).
1.12 Conclusions
Despite struggling to achieve enantioselectivity, this transformation is of potential promise and interest. Using substrates that are accessible in only two steps from commercially abundant starting materials, we can access densely functionalized cyclopropanes in high diastereoselectivity. These cyclopropanes have many orthogonal synthetic handles to be further manipulated toward more complicated products. In the future, additional efforts to render this transformation enantioselective will be explored. Additionally, expansion of these conditions to new substrates to afford highly functionalized cyclopropanes in high diastereoselectivity is an area of interest for our group.
74
1.13 ExperimentalMethods: All reactions were carried out in glassware that had been purged with nitrogen.
Proton and carbon magnetic resonance spectra (1H NMR and 13C NMR) were recorded on either a Bruker model DRX 400 or 600 spectrometer (1 H NMR at 400 or 600 MHz and 13C NMR at 100 or 150 MHz) with solvent resonance as the internal standard (1H NMR: CDCl3 at 7.26 ppm and 13C-NMR: CDCl3 at 77.0 ppm). 1H NMR data are reported as follows: chemical shift, multiplicity (abbreviations: s = singlet, br s = broad singlet, d = doublet, dd = doublet of doublets, ddd = doublet of doublet of doublets, dt = doublet of triplets, t = triplet, td = triplet of doublets, tt = triplet of triplets, qt = quintet, and m = multiplet), coupling constant (Hz) and integration. Thin layer chromatography (TLC) was performed on Sorbtech plastic-backed 0.20 mm silica gel 60 plates. Visualization was accomplished with UV light and potassium permanganate (KMnO4) solution, followed by heating. Flash chromatography was performed under positive air pressure using Siliaflash-P60 silica gel (40-63 μm) purchased from Silicycle.
Materials: Nitrogen was dried by passage through anhydrous calcium sulfate with 3% cobalt chloride as indicator (commercial Drierite). Solvents were purged with nitrogen and purified under a positive pressure of dry nitrogen by a SG Waters purification system: dichloromethane (EMD Millipore), diethyl ether (EMD Millipore), THF (EMD Millipore), and toluene (EMD Millipore) were passed through activated alumina columns. All other reagents and solvents were purchased from commercial sources and used as received.
ethyl (Z)-2-benzoyl-4-bromo-5-methylhex-2-enoate (1.90): A solution of ethyl benzoyl acetate (8.21 g, 1 equiv, 42.7 mmol) and isovaleraldehyde (4.42 g, 1.20 equiv, 51.3 mmol) in EtOH (40 mL) was cooled to 0 ℃. Piperidine (36.4 mg, 0.01 equiv, 0.427 mmol) was added. The reaction was stirred at 0 ℃ for 5 h. The reaction was diluted with water and Et2O. The aqueous layer was extracted twice with Et2O; organic layers were washed twice with water, dried with Na2SO4 and concentrated in vacuo. The intermediate, ethyl (Z)-2-benzoyl-5- methylhex-2-enoate, was taken onto bromination without purification.
75
Ethyl (Z)-2-benzoyl-5-methylhex-2-enoate (10.75 g, 1 equiv, 41.3 mmol) was dissolved in acetonitrile (80 mL) in a flame-dried round bottom flask. NBS (7.35 g, 1 equiv, 41.3 mmol) was slowly added. The reaction was heated to reflux for 1 h. The reaction was cooled to rt, diluted with Et2O, and washed thrice with water. The organic layer was dried with MgSO4, filtered, and concentrated. The crude product was purified via silica gel chromatography (5% EtOAc:hexanes) to afford 1.90 as a pale-yellow oil. Analytical data for 1.90: 1H NMR (400 MHz, CDCl3) 7.92-7.9 (m, 2H), 7.63 (m, 1H), 7.53-
7.49 (m, 2H), 7. 24 (d, J = 11.6 Hz, 1H), 4.30 (dd, J = 6.4, 12.0 Hz, 1H), 4.23-4.17 (m, 2H), 2.03 (m, 1H), 1.16 (t, J = 7.2 Hz, 3H), 1.05 (dd, J = 6.8, 12.0 Hz, 6H).
General procedure for optimization of organocatalytic nitromethane addition to 1.90 to afford ethyl 1-benzoyl-2-isopropyl-3-(nitromethyl)cyclopropane-1- carboxylate (1.91): Substrate 1.90 (33.9 mg, 0.10 mmol, 1 equiv), solvent (1 mL), and nitromethane (128 mg, 21 equiv, 2.10 mmol) were added to a flame dried test tube. The reaction was cooled to desired temperature, and appropriate catalyst (20 mol %) was added. Additive (1.2 equiv, 0.12 mmol) was added as necessary. The reaction was allowed to stir at the desired temperature for 24 hours. After 24 hours, the reactions were quenched with 0.5M TFA in toluene (0.5 mL) at the reaction temperature, filtered through a silica plug with Et2O, and concentrated. The products were all purified on silica gel (2.5% EtOAc:hexanes, followed by 5% EtOAc) to afford the desired products that could be analyzed for diastereo- and enantioselectivity. Analytical data for 1.91: 1H NMR (400 MHz,
CDCl3) 7.75 (d, J = 6.8 Hz, 2H), 7.46-7.38 (m, 3H), 5.15 (dt, J = 4.0, 9.2 Hz, 1H), 4.70 (dd, J = 9.6, 12.0 Hz, 1H), 4.40 (dd, J = 4.0, 12.4 Hz, 1H), 4.16 (q, J = 7.2 Hz, 2H), 3.05 (t, J = 3.2 Hz, 1H), 2.29 (m, 1H), 1.22 (t, J = 7.2 Hz, 3H), 0.99 (dd, J = 7.2, 28.4 Hz, 6H).
General procedure for optimization of phase-transfer nitromethane addition to 1.90 to afford ethyl 1-benzoyl-2-isopropyl-3-(nitromethyl)cyclopropane-1- carboxylate (1.91): 1.90 (33.9 mg, 1 equiv, 0.10 mmol) dissolved in the appropriate solvent (1 mL) in a flamed dried vial. The appropriate catalyst (0.1 equiv, 0.01 mmol) and nitromethane
76
(30.5 mg, 5 equiv, 0.50 mmol) were added. The appropriate base (5.0 equiv, 0.50 mmol) was added and the reaction was allowed to stir at rt for 16 h. The reaction was poured onto sat. aq. NaHCO3 (3 mL), and extracted thrice with DCM. The combined organic layers were dried with Na2SO4, filtered, and concentrated. The reaction was purified via silica gel chromatography (2.5 % EtOAc:hexanes to 5% EtOAc:hexanes) to afford 1.91 as a mixture of diastereomers (see optimization chart). See 1H NMR characterization above.
77
REFERENCES(1) Reviews on dynamic kinetic resolution: (a) Huerta, F. F.; Minidis, A. B. E.; Bäckvall, J.-E. Racemisation in Asymmetric Synthesis. Dynamic Kinetic Resolution and Related Processes in Enzyme and Metal Catalysis. Chem. Soc. Rev. 2001, 30, 321–331. (b) Pellissier, H. Recent Developments in Dynamic Kinetic Resolution. Tetrahedron 2011, 67, 3769–3802. (c) Bhat, V.; Welin, E. R.; Guo, X.; Stoltz, B. M. Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations. Chem. Rev. 2017, 117, 4528–4561. (d) Bartlett, S. L.; Johnson, J. S. Synthesis of Complex Glycolates by Enantioconvergent Addition Reactions. Acc. Chem. Res. 2017, 50, 2284–2296. (e) Pellissier, H. Dynamic Kinetic Resolution. Tetrahedron 2003, 59, 8291–8327. (f) Caddick, S.; Jenkins, K. Dynamic Resolutions in Asymmetric Synthesis. Chem. Soc. Rev. 1996, 25, 447–456.
(2) Noyori, R.; Ikeda, T.; Ohkuma, T.; Widhalm, M.; Kitamura, M.; Takaya, H.; Akutagawa, S.; Sayo, N.; Saito, T.; Taketomi, T.; et al. Stereoselective Hydrogenation via Dynamic Kinetic Resolution. J. Am. Chem. Soc. 1989, 111, 9134–9135.
(3) Shimizu, H.; Nagasaki, I.; Matsumura, K.; Sayo, N.; Saito, T. Developments in Asymmetric Hydrogenation from an Industrial Perspective. Acc. Chem. Res. 2007, 40, 1385-1393.
(4) Rodríguez, S.; Schroeder, K. T.; Kayser, M. M.; Stewart, J. D. Asymmetric Synthesis of β- Hydroxy Esters and α-Alkyl-β-Hydroxy Esters by Recombinant Escherichia Coli Expressing Enzymes from Baker’s Yeast. J.Org. Chem. 2000, 65, 2586–2587.
(5) Steward, K. M.; Gentry, E. C.; Johnson, J. S. Dynamic Kinetic Resolution of α-Keto Esters via Asymmetric Transfer Hydrogenation. J. Am. Chem. Soc. 2012, 134, 7329–7332.
(6) Steward, K. M.; Corbett, M. T.; Goodman, C. G.; Johnson, J. S. Asymmetric Synthesis of Diverse Glycolic Acid Scaffolds via Dynamic Kinetic Resolution of α-Keto Esters. J. Am. Chem. Soc. 2012, 134, 20197–20206.
(7) Goodman, C. G.; Do, D. T.; Johnson, J. S. Asymmetric Synthesis of Anti -β-Amino-α-Hydroxy Esters via Dynamic Kinetic Resolution of β-Amino-α-Keto Esters. Org. Lett. 2013, 15, 2446– 2449.
(8) Corbett, M. T.; Johnson, J. S. Dynamic Kinetic Asymmetric Transformations of β-Stereogenic α-Ketoesters by Direct Aldolization. Angew. Chemie Int. Ed. 2014, 53, 255–259.
(9) Goodman, C. G.; Walker, M. M.; Johnson, J. S. Enantioconvergent Synthesis of Functionalized γ-Butyrolactones via (3 + 2)-Annulation. J. Am. Chem. Soc. 2015, 137, 122–125.
(10) Zavesky, B. P.; Johnson, J. S. Direct Zinc(II)-Catalyzed Enantioconvergent Additions of Terminal Alkynes to α-Keto Esters. Angew. Chem. Int. Ed. 2017, 56, 8805–8808.
(11) Bartlett, S. L.; Keiter, K. M.; Johnson, J. S. Synthesis of Complex Tertiary Glycolates by Enantioconvergent Arylation of Stereochemically Labile α-Keto Esters. J. Am. Chem. Soc. 2017, 139, 3911–3916.
78
(12) Orue, A.; Uria, U.; Roca-López, D.; Delso, I.; Reyes, E.; Carrillo, L.; Merino, P.; Vicario, J. L. Racemic Hemiacetals as Oxygen-Centered Pronucleophiles Triggering Cascade 1,4- Addition/Michael Reaction through Dynamic Kinetic Resolution under Iminium Catalysis. Development and Mechanistic Insights. Chem. Sci. 2017, 8, 2904–2913.
(13) Pandey, G.; Adate, P. A.; Puranik, V. G. Organocatalytic Dynamic Kinetic Resolution via Conjugate Addition: Synthesis of Chiral Trans-2,5-Dialkylcyclohexanones. Org. Biomol. Chem. 2012, 10, 8260–8267.
(14) Misaki, T.; Tatsumi, T.; Okamoto, T.; Hayashi, Y.; Jin, N.; Sugimura, T. Stereoconvergent 1,4- Addition Reaction of 5 H -Oxazol-4-Ones with E, Z Isomeric Mixture of Alkylidene β- Ketoesters Catalyzed by Chiral Guanidines. Chem. - A Eur. J. 2018, 24, 9778–9782.
(15) Evans, D. A.; Rovis, T.; Kozlowski, M. C.; Downey, C. W.; Tedrow, J. S. Enantioselective Lewis Acid Catalyzed Michael Reactions of Alkylidene Malonates. Catalysis by C2‐Symmetric Bis (Oxazoline) Copper (II) Complexes in the Synthesis. J. Am. Chem. Soc. 2000, 122, 9134– 9142.
(16) Zhuang, W.; Hansen, T.; Jørgensen, K. A. Catalytic Enantioselective Alkylation of Heteroaromatic Compounds Using Alkylidene Malonates. Chem. Commun. 2001, 347–348. (17) Zhou, J.; Tang, Y. Enantioselective Friedel–Crafts Reaction of Indoles with Arylidene
Malonates Catalyzed by iPr-Bisoxazoline–Cu(OTf)2. Chem. Commun. 2004, 432–433.
(18) Sun, Y.-J.; Li, N.; Zheng, Z.-B.; Liu, L.; Yu, Y.-B.; Qin, Z.-H.; Fu, B. Highly Enantioselective Friedel Crafts Reaction of Indole with Alkylidenemalonates Catalyzed by Heteroarylidene Malonate-Derived Bis(Oxazoline) Copper(II) Complexes. Adv. Synth. Catal. 2009, 351, 3113– 3117.
(19) Zhou, J.; Tang, Y. Sidearm Effect: Improvement of the Enantiomeric Excess in the Asymmetric Michael Addition of Indoles to Alkylidene Malonates. J. Am. Chem. Soc. 2002, 124, 9030– 9031.
(20) Zhou, J.; Ye, M. C.; Huang, Z. Z.; Tang, Y. Controllable Enantioselective Friedel-Crafts Reaction between Indoles and Alkylidene Malonates Catalyzed by Pseudo-C3-Symmetric Trisoxazoline Copper(II) Complexes. J. Org. Chem. 2004, 69, 1309–1320.
(21) Cardillo, G.; Gentilucci, L.; Gianotti, M.; Kim, H.; Perciaccante, R.; Tolomelli, A. Conjugate Addition of Hydroxylamino Derivatives to Alkylidene Malonates in the Presence of Chiral Lewis Acids. Tetrahedron Asymmetry 2001, 12, 2395–2398.
(22) Cardillo, G.; Fabbroni, S.; Gentilucci, L.; Gianotti, M.; Percacciante, R.; Tolomelli, A. Enantioselective Synthesis of Aziridine 2,2-Dicarboxylates. Part I: Copper(II)-Bisoxazoline Complex-Catalysed Michael Reaction on Alkylidene Malonates. Tetrahedron Asymmetry 2002, 13, 1407–1410.
(23) Alexakis, A.; Benhaim, C. Asymmetric Conjugate Addition to Alkylidene Malonates. Tetrahedron Asymmetry 2001, 12, 1151–1157.
79
(24) Magar, D. R.; Chang, C.; Ting, Y. F.; Chen, K. Highly Enantioselective Conjugate Addition of Ketones to Alkylidene Malonates Catalyzed by a Pyrrolidinyl-Camphor-Derived Organocatalyst. European J. Org. Chem. 2010, 2010, 2062–2066.
(25) Zhao, G. L.; Vesely, J.; Sun, J.; Christensen, K. E.; Bonneau, C.; Córdova, A. C. Organocatalytic Highly Enantioselective Conjugate Addition of Aldehydes to Alkylidine Malonates. Adv. Synth. Catal. 2008, 350, 657–661.
(26) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry Part B: Reactions and Synthesis; Plenum Press: New York, 1990; pp 13-16.
(27) Select examples. (a) Vancomycin: Sheldrick, G. M.; Jones, P. G.; Kennard, O.; Williams, D. H.; Smith, G. A. Structure of vancomycin and its complex with acetyl-D-alanyl-D-alanine. Nature 1978, 271, 223-225. (b) Polymastiamide A: Kong, F.; Andersen, R. J. Polymastiamide A, a novel steroid/amino acid conjugate isolated from the Norwegian marine sponge Polymastia boletiformis (Lamarck, 1815) J. Org. Chem. 1993, 58, 6924-6927. (c) Chloropeptin I and II: Hegde, V. R.; Dai, P.; Patel, M.; Gullo, V. P. Complestatin and chloropeptin I, condensed aromatic peptides from two strains of streptomycetes Tetrahedron Lett. 1998, 39, 5683-5684. (28) Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini, M. Conjugate Additions of Nitroalkanes
to Electron-Poor Alkenes: Recent Results. Chem. Rev. 2005, 105, 933–972.
(29) Funabashi, K.; Saida, Y.; Kanai, M.; Arai, T.; Sasai, H.; Shibasaki, M. Catalytic asymmetric Michael addition of nitromethane to enones controlled by (R)-LPB. Tetrahedron Lett. 1998, 39, 7557-7558.
(30) Halland, N.; Hazell, R. G.; Jørgensen, K. A. Organocatalytic Asymmetric Conjugate Addition of Nitroalkanes to α,β-Unsaturated Enones Using Novel Imidazoline Catalysts. J. Org. Chem. 2002, 67, 8331–8338.
(31) Vakulya, B.; Varga, S.; Csámpai, A.; Soós, T. Highly Enantioselective Conjugate Addition of Nitromethane to Chalcones Using Bifunctional Cinchona Organocatalysts. Org. Lett. 2005, 7, 1967–1969.
(32) Dong, X. Q.; Teng, H. L.; Wang, C. J. Highly Enantioselective Direct Michael Addition of Nitroalkanes to Nitroalkenes Catalyzed by Amine Thiourea Bearing Multiple Hydrogen- Bonding Donors. Org. Lett. 2009, 11, 1265–1268.
(33) Wang, J.; Li, H.; Zu, L.; Jiang, W.; Wang, W. Organocatalytic, Enantioselective Conjugate Addition of Nitroalkanes to Nitroolefins. Adv. Synth. Catal. 2006, 348, 2047–2050.
(34) Kwiatkowski, P.; Cholewiak, A.; Kasztelan, A. Efficient and Highly Enantioselective Construction of Trifluoromethylated Quaternary Stereogenic Centers via High-Pressure Mediated Organocatalytic Conjugate Addition of Nitromethane to β,β-Disubstituted Enones. Org. Lett. 2014, 16, 5930–5933.
(35) Inokuma, T.; Hoashi, Y.; Takemoto, Y. Thiourea-Catalyzed Asymmetric Michael Addition of Activated Méthylene Compounds to α,β-Unsaturated Imides: Dual Activation of Imide by Intra- and Intermolecular Hydrogen Bonding. J. Am. Chem. Soc. 2006, 128, 9413–9419.
80
(36) Hoashi, Y.; Okino, T.; Takemoto, Y. Enantioselective Michael Addition to α,β-Unsaturated Imides Catalyzed by a Bifunctional Organocatalyst. Angew. Chemie - Int. Ed. 2005, 44, 4032– 4035.
(37) Grayson, M. N. Mechanism and Origins of Stereoselectivity in the Cinchona Thiourea- and Squaramide-Catalyzed Asymmetric Michael Addition of Nitroalkanes to Enones. J. Org. Chem. 2017, 82, 4396–4401.
(38) Horwitz, M. A.; Fulton, J. L.; Johnson, J. S. Enantio- and Diastereoselective Organocatalytic Conjugate Additions of Nitroalkanes to Enone Diesters. Org. Lett. 2017, 19, 5783–5785. (39) Farley, A. J. M.; Sandford, C.; Dixon, D. J. Bifunctional Iminophosphorane Catalyzed
Enantioselective Sulfa-Michael Addition to Unactivated α-Substituted Acrylate Esters. J. Am. Chem. Soc. 2015, 137, 15992–15995.
(40) Yang, J.; Farley, A. J. M.; Dixon, D. J. Enantioselective Bifunctional Iminophosphorane Catalyzed Sulfa-Michael Addition of Alkyl Thiols to Unactivated β-Substituted-α,β- Unsaturated Esters. Chem. Sci. 2016, 8, 606–610.
(41) Formica, M.; Sorin, G.; Farley, A. J. M.; Díaz, J.; Paton, R. S.; Dixon, D. J. Bifunctional Iminophosphorane Catalysed Enantioselective Sulfa-Michael Addition of Alkyl Thiols to Alkenyl Benzimidazoles. Chem. Sci. 2018, 9, 6969–6974.
(42) Núñez, M. G.; Farley, A. J. M.; Dixon, D. J. Bifunctional Iminophosphorane Organocatalysts for Enantioselective Synthesis: Application to the Ketimine Nitro-Mannich Reaction. J. Am. Chem. Soc. 2013, 135, 16348–16351.
(43) Novikov, R. A.; Korolev, V. A.; Timofeev, V. P.; Tomilov, Y. V. New Dimerization and Cascade Oligomerization Reactions of Dimethyl 2-Phenylcyclopropan-1,1-Dicarboxylate Catalyzed by Lewis Acids. Tetrahedron Lett. 2011, 52, 4996–4999.
(44) Novikov, R. A.; Tarasova, A. V.; Tomilov, Y. V. GaCl3-Mediated Isomerization of Donor- Acceptor Cyclopropanes into (2-Arylalkylidene)Malonates. Synlett 2016, 27, 1367–1370. (45) Uraguchi, D.; Sakaki, S.; Ooi, T. Chiral Tetraaminophosphonium Salts-Mediated Asymmetric
Direct Henry Reaction. J. Am. Chem. Soc. 2007, 14, 12392–12393.
(46) University of Wisconsin, Department of Chemistry. Bordwell pKa Table (Acidity in DMSO). https://www.chem.wisc.edu/areas/reich/pkatable/ (accessed Jun 10, 2019).
(47) Noerenberg, H.; Kratzin, H.; Boldt, P.; Sheldrick, W. S. Radikalische Additionen, V. Addition von Brommalononitril an Alkine. Synthese Und Struktur von (E)-3,4-Diphenyl-1,3,5- Hexatrien-1,1,6,6-Tetracarbonitril. Chem. Ber. 2007, 110, 1284–1293.
(48) Lee, D.; Kim, D.; Yun, J. Highly Enantioselective Conjugate Reduction of β,β-Disubstituted α,β-Unsaturated Nitriles. Angew. Chemie - Int. Ed. 2006, 45, 2785–2787.
(49) Lee, J. E.; Yun, J. Catalytic Asymmetric Boration of Acyclic α,β-Unsaturated Esters and Nitriles. Angew. Chemie - Int. Ed. 2008, 47, 145–147.
81
(50) Feringa, B. L.; Badorrey, R.; Pena, D.; Harutyunyan, S. R.; Minnaard, A. J. Asymmetric Catalysis Special Feature Part II: Copper-Catalyzed Asymmetric Conjugate Addition of Grignard Reagents to Cyclic Enones. Proc. Natl. Acad. Sci. 2004, 101, 5834–5838.
(51) López, F.; Harutyunyan, S. R.; Minnaard, A. J.; Feringa, B. L. Copper-Catalyzed Enantioselective Conjugate Addition of Grignard Reagents to Acyclic Enones. J. Am. Chem. Soc. 2004, 126, 12784–12785.
(52) López, F.; Harutyunyan, S. R.; Meetsma, A.; Minnaard, A. J.; Feringa, B. L. Copper-Catalyzed Enantioselective Conjugate Addition of Grignard Reagents to α,β-Unsaturated Esters. Angew. Chemie - Int. Ed. 2005, 44, 2752–2756.
(53) Des Mazery, R.; Pullez, M.; Lopez, F.; Harutyunyan, S. R.; Minnaard, A. J.; Feringa, B. L. An Iterative Catalytic Route to Enantiopure Deoxypropionate Subunits: Asymmetric Conjugate Addition of Grignard Reagents to α,β-Unsaturated Thioesters. J. Am. Chem. Soc. 2005, 127, 9966–9967.
(54) Ruiz, B. M.; Geurts, K.; Fernández-Ibáñez, M. Á.; Horst, B. Ter; Minnaard, A. J.; Feringa, B. L. Highly Versatile Enantioselective Conjugate Addition of Grignard Reagents to α,β- Unsaturated Thioesters. Org. Lett. 2007, 9, 5123–5126.
(55) Lima, C. G. S.; Monteiro, J. L.; de Melo Lima, T.; Weber Paixão, M.; Corrêa, A. G. Angelica Lactones: From Biomass-Derived Platform Chemicals to Value-Added Products. ChemSusChem. 2018, 11, 25–47.
(56) Select examples of a-angelica lactone isomerization: (a) Panfil, I.; Abramski, W.; Chmielewski, M. Conjugate Ad-dition of Hydroxylamines to 4-Subtituted Butenolides. J. Carbohydrate Chemistry, 1998, 17, 1395-1403. See also: (b) Wu, Y.; Singh, R. P.; Deng, L. Asymmetric Olefin Isomerization of Butenolides via Proton Transfer Catalysis by an Organic Molecule. J. Am. Chem. Soc. 2011, 133, 12458–12461. (c) Sorg, A.; Blank, F.; Brückner, R. Stepwise Cross- Couplings of a Dibromo-γ-Methylenebutenolide as an Access to Z -Configured α-Alkenyl-γ- Alkylidenebutenolides. Straightforward Synthesis of the Antibi-otic Lissoclinolide. Synlett 2005, 2005, 1286–1290. (d) Jones, C. R.; Greenhalgh, M. D.; Bame, J. R.; Simpson, T. J.; Cox, R. J.; Marshall, J. W.; Butts, C. P. Subtle Temperature-Induced Chang-es in Small Molecule Conformer Dynamics – Observed and Quantified by NOE Spectroscopy. Chem. Commun. 2016, 52, 2920–2923. (e) Lindström, M.; Hedenström, E.; Bouilly, S.; Ve-lonia, K.; Smonou, I. Synthesis of Diastereo- and Enantiomerical-ly Pure Anti-3-Methyl-1,4-Pentanediol via Lipase Catalysed Ac-ylation. Tetrahedron: Asymmetry 2005, 16, 1355–1360. (f) Zhou, L.; Lin, L.; Ji, J.; Xie, M.; Liu, X.; Feng, X. Catalytic Asymmetric Vinylogous Mannich-Type (AVM) Reaction of Nonactivated α-Angelica Lactone. Org. Lett. 2011, 13, 3056–3059. (g) Newland, M. J.; Rea, G. J.; Thüner, L. P.; Henderson, A. P.; Golding, B. T.; Rickard, A. R.; Barnes, I.; Wenger, J. Photochemistry of 2-Butenedial and 4-Oxo-2-Pentenal under Atmospheric Boundary Layer Conditions. Phys. Chem. Chem. Phys. 2019, 21, 1160–1171. (f) Mathews, C. J.; Taylor, J.; Tyte, M. J.; Worthington, P. A. Microwave Assisted Suzuki Reactions for the Preparation of the Antifungal 3-Aryl-5-Methyl-2,5-Dihydrofuran-2-Ones. Synlett 2005, 2005, 538–540. (57) Mascal, M.; Dutta, S.; Gandarias, I. Hydrodeoxygenation of the Angelica Lactone Dimer, a
Cellulose-Based Feedstock: Simple, High-Yield Synthesis of Branched C7 -C10 Gasoline-like