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Org. Synth. 2009, 86, 287
DOI: 10.15227/orgsyn.086.0287
LOW PRESSURE CARBONYLATION OF EPOXIDES TO β-LACTONES
Submitted by Submitted by John W. Kramer, Daniel S. Treitler, and Geoffrey W. Coates1.
Checked by Checked by Scott E. Denmark and Andrew J. Hoover.
1. Procedure
Caution: Carbon monoxide is a highly toxic gas. All manipulations with carbon monoxide must be performed in a well-ventilated fume hood in the presence of a carbon monoxide detector.
In an argon-filled glove box, racemic 1,2-epoxy-3-phenoxypropane (5.00 g, 33.3 mmol) (Note 1) and dimethoxyethane (DME, 8.5 mL) (Note 2) are combined in an oven-dried, 85-mL Lab-Crest® Pressure Reaction Vessel (Note 3) equipped with a magnetic stir bar. The catalyst, [(salph)Cr(THF)2][Co(CO)4] (1, 0.150 g, 0.1667 mmol, 0.4975 mol %) (Note 4) is weighed into an oven-dried, 20-mL vial and dissolved in 8.0 mL of DME. This catalyst solution is drawn into an oven-dried, 10-mL gastight syringe, and the syringe needle is embedded into a septum to exclude air upon removal from the glove box.
In a well-ventilated fume hood, the Lab-Crest® Pressure Reaction Vessel is connected to a cylinder of carbon monoxide (Notes 3 and 5) via a Swagelok quick connect attachment). The reactor is then submerged into a water bath at 20 °C °C and concurrently pressurized with CO to 20 psi (Note 6) with CO. After five minutes in the water bath, the catalyst solution is added to the reactor through a septum over the injection port (Note 7). The reactor is then pressurized to 100 psi CO and the dark red solution is stirred while the temperature of the water bath is held between 20-265 °C (Note 8). The CO pressure is maintained by repressurizing the reactor to 100 psi when the pressure dropsped below 80 psito 85 psi. After 6 h, the reactor is carefully vented in the fume hood and the reaction mixture is removed transferred to a 100-mL round-bottomed flask.
The crude reaction mixture is evacuated to drynessconcentrated by rotary evaporation (20 °C, 5 mmHg) and is then dissolved in 13 mL of dichloromethane (Note 9). This solution is added poured into a medium-pore frit (9 cm diameter) packed with dry silica gel (4 cm) (Note 10). The lactone product is eluted with pure CH2Cl2 dichloromethane (1.1 L) and the filtrate is concentrated by rotary evaporation (15 °C, 14 mmHg) and then under high vacuum (26 °C, 0.33 mmHg) to afford 5.61–5.77 g (95-97%) of 4-phenoxymethyl-2-propiolactone as a white solid (Note 11). The lactone is dissolved in boiling CH2Cl2 diethyl ether (12 250 mL) in a 500-mL round-bottomed flask, and ,the solution is allowed to cool at cooling to 25 25 °C for 15 minutes, and is then submerged in a 10 °C water bath. Crystals formed within 7 minutes, and after 1 hour in the bath the flask is placed in a -20 °C refrigeratorfreezer at -20 °C for 12 hours. The supernatant is carefully decanted, and the crystals are washed with 10 mL of cold (−40 °C) diethyl ether,, which is decanted. The rResidual solvent is removed under vacuum (0.5 mmHg, 25 °C, 0.5 mmHg) to afford 5.13 g (86%) of 4-phenoxymethyl-2-propiolactone. The mother liquor is concentrated under vacuum (0.2 mmHg, 25 °C, 0.2 mmHg) to afford 568 mg of an off white solid,, which is recrystallized in the same manner as the crude productdescribed above, except that 21 mL of boiling ether is used., Tthe solution is cooled at −20 °C for 2.5 hours instead of 12 hours, and the crystals are washed with 3 mL of −40 °C diethyl ether, to afford 0.48 g (8%) of 4-phenoxymethyl-2-propiolactone. The two crops are combined and residual solvent is removed under vacuum (0.325 mmHg, 25 °C, 0.325 mmHg), to afford 5.53 g (93%) of analytically pure 4-phenoxymethyl-2-propiolactone as colorless needles (Note 12).
2. Notes
1. 1,2-Epoxy-3-phenoxypropane is purchased from Aldrich Chemical Co., Inc. (99%) and is dried by stirring over CaH2 under a nitrogen atmosphere for at least one week, degassed with three freeze-pump-thaw cycles, and vacuum transferred prior to use.vacuum distilled, and transferred into an argon glove box prior to use. The submitters performed the reaction in a nitrogen-filled glove box.
2. DME is transferred vacuum -distilled under reduced pressure from a sodium/benzophenone ketyl prior to use.and transferred into an argon glove box prior to use.
3. See Figures 1 and 2 for the assembly of the pressure apparatus. The Lab-Crest® pPressure rReaction vVessel (A) and shield (B) was are purchased from Andrews Glass Co. (part # 110207 0003, includes A, B, and fittings C-F) and fitted with a needle valve adaptor (SS 1/8" NPT, Andrews Glass Co. part #110957 0001, G), which is fitted with a connector (male, SS, 1/8" NPT, 1/4" Swagelok Tube fitting, H). This connector is coupled to a union cross (SS, 1/4" Swagelok Tube fittings, I). isTwo of the union cross joints are coupled to two Swagelok needle valves (SS, 1/4" Swagelok Tube fittings, J-K). Valve K is fitted with a septum (L), and valve J is connected to a tube from a carbon monoxide tank. The last union cross joint is coupled to an elbow (SS, the two ends are 1/4" Swagelok tube fitting and 1/4" NPT male, M), which is connected to a tee-joint (SS, all female 1/4" joints, N). The tee-joint is connected to a pressure release valve (SS, 1/4" NPT, Swagelok part #SS-RL3M4-S4, O) and a pressure gauge (brass, 0-200 psi, Wika part #111.11.53, P). 1" SS tube sections (Q) were used to couple all Swagelok tube fittings. The threadsings of H, M, O and P were wrapped with Teflon tape. pressure guage (0-100 psi), resettable pressure release valve, injector port, and a female Swagelok quick connect. See reference 5f for a picture of the reactor. Contact vendor for pressure specifications and Aalways shield glass reactors when under pressure.
4. The submitters prepared catalyst 1 according to reference 5f. The checkers purchased catalyst 1 from Aldrich Chemical Co., Inc. is commercially available from Aldrich (catalog # 674680), opened it only in an argon glove box, and used it as received.
5. The submitters purchased rResearch-grade carbon monoxide (99.99% min) was purchased from Matheson and used as received.it as received. The checkers purchased CP grade carbon monoxide (99.5%) from Matheson-Trigas and used it as received.
6. Pressurization of the cylinder is done by overpressurizing the apparatus, closing valve J and adjusting the internal pressure with the release valve O, Figure 3.
7. The catalyst solution is added via syringe through the septum covered port in valve K, Figure 4.
8. Pressurization of the cylinder is done by overpressurizing the apparatus, closing valve J and adjusting the internal pressure with the release valve O, Figure 5.
9. The submitters used dichloromethane without purification. The checkers purchased dichloromethane (ACS reagent grade, ≥99.5%) from Aldrich Chemical Co., Inc. and used it as received.
10. The submitters used MP SiliTech silica gel (neutral, 45-55 μm particle size, pore diameter of 60 Å) purchased was purchased from MP Biomedicals. The checkers used Merck silica gel (grade 9385, 60 mesh) purchased from Aldrich.
11. In one experiment, the checkers found that thethe product is contaminated with 1% of a ketone side product.
12. The product exhibits the following physicochemical properties: mp 75–76 °C; 1H NMR pdf (500 MHz, CDCl3) δ: 3.57 (dd, J = 16.3, 4.8 Hz, 1 H), 3.61 (dd, J = 16.3, 5.8 Hz, 1 H), 4.86 (dddd, J = 5.0 Hz, 1 H), 6.93 (d, J = 8.0 Hz, 2 H) 7.01 (t, J = 7.3 Hz, 1 H), 7.31 (t, J = 8.0 Hz, 2 H); 13C NMR pdf (126 MHz, CDCl3) δ: 40.4, 67.6, 68.6, 115.0, 122.1, 130.0, 158.3, 167.5; IR (CH2Cl2) cm-1: 3063 (w), 3044 (w), 2925 (w), 2870 (w), 1833 (s), 1600 (m), 1591 (m), 1497 (m), 1453 (w), 1409 (w), 1366 (w), 1334 (w), 1303 (m), 1245 (s), 1175 (w), 1114 (s), 1052 (w), 972 (m), 926 (w), 887 (w), 838 (m), 739 (m), 692 (m); MS (EI), m/z (relative intensity): 179 (11), 178 (100), 176 (11), 136 (31), 108 (11), 107 (70), 94 (62), 85 (11), 79 (14), 77 (63), 65 (16); exact mass calcd for (C10H10O3: 178.0630. Found: 178.0632;) 178.0630; measured 178.0630, fit 0.0 ppm. Anal. Calcd for C10H10O3: C, 67.41; H, 5.66. Found: C, 67.10; H, 5.62.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
β-Lactones find a wide variety of uses in organic synthesis as both attractive intermediates2 and natural product targets.3 Since the initial report of epoxide carbonylation to β-lactones over a decade ago,4 the method has emerged as a versatile synthetic route and has been elaborated to include a variety of catalyst systems applicable under a range of conditions.5
However, until recently5f all of these systems required high pressures of CO (>100 psi) for efficient carbonylation, necessitating the use of stainless steel reactors and other high-pressure equipment. The procedure presented herein allows for the carbonylation of epoxides to β-lactones with comparable efficiency to other systems but at significantly lower CO pressures.
Our initial work focused on epoxide carbonylation at 100 psi CO which allows the use of a glass-sealed reactor, a significantly cheaper and more accessible alternative to a stainless steel reactor. This method worked well under optimized conditions on a 2-mmol scale for a variety of functionally diverse epoxides (Table 1, entries 1-11). In each case, β-lactone is formed as the exclusive product and is isolated from the catalyst in high yield using the method described in the Procedure. Further, the reaction proceeds with retention of stereochemistry (entry 3),6 so enantiopure β-lactones can be prepared from enantiopure epoxides.
Table 1. Synthesis of functionally diverse β-lactones at 100 psi COa
Table 1. Synthesis of functionally diverse β-lactones at 100 psi COa
a All reactions performed on a 2 mmol scale with 1 mol % 1. b Isolated yields of β-lactones. c Diethyl ether is reaction solvent and reaction time is 2 h. d 10 mL Hexanes added to crude reaction mixture before filtering through silica. e The volatility of BBL caused the anomalously low isolated yield upon purification. f Both epoxide and β-lactone >>99% ee; determined by chiral GC. g Contains 3% γ-lactone.7
Figure 1. Components of pressure reactor.
Figure 1. Components of pressure reactor.
Figure 2. Assembled pressure reactor with CO cylinder.
Figure 2. Assembled pressure reactor with CO cylinder.
Figure 3. Adjusting pressure to 20 psi.
Figure 3. Adjusting pressure to 20 psi.
Figure 4. Valve orientation for injecting the catalyst solution.
Figure 4. Valve orientation for injecting the catalyst solution.
Figure 5. Pressure maintained at 100 psi throughout the procedure.
Figure 5. Pressure maintained at 100 psi throughout the procedure.
References and Notes
  1. Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301.
  2. For a review of β-lactones in organic chemistry, see: Wang, Y.; Tennyson, R. L.; Romo. D. Heterocycles 2004, 64, 605-658.
  3. Pommier, A.; Pons, J.-M. Synthesis 1995, 729-744.
  4. Drent, E.; Kragtwijk, E. European Patent Application EP 577206; Chem. Abstr. 1994, 120, 191517c.
  5. (a) Lee, J. T.; Thomas, P. J.; Alper, H. J. Org. Chem. 2001, 66, 5424-5426. (b) Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2002, 124, 1174-1175. (c) Mahadevan, V.; Getzler, Y. D. Y. L.; Coates, G. W. Angew. Chem., Int. Ed. 2002, 41, 2781-2784. (d) Allmendinger, M.; Zintl, M.; Eberhardt, R.; Luinstra, G. A.; Molnar, F.; Rieger, B. J. Organomet. Chem. 2004, 689, 971-979. (e) Schmidt, J. A. R.; Mahadevan, V.; Getzler, Y. D. Y. L.; Coates, G. W. Org. Lett. 2004, 6, 373-376. (f) Kramer, J. W.; Lobkovsky, E. B.; Coates, G. W. Org. Lett. 2006, 8, 3709-3712. (g) Rowley, J. M.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2007, 129, 4948-4960.
  6. A thorough mechanistic study of a closely related catalyst system hasbeen completed. See: Church, T. L.; Getzler, Y. D. Y. L.; Coates, G. W. J. Am. Chem. Soc. 2006, 128, 10125-10133.
  7. γ-Lactones are observed as rearranged side products during the carbonylation of glycidyl esters. For mechanistic insight, see: Schmidt, J. A. R.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426-11435.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

1,2-Epoxy-3-phenoxypropane: oxirane, 2-(phenoxymethyl)-; (122-60-1)

[N,,N'-Bis(3,5-di-tert-butylsalicylidene)-1,2-phenylenediamino-chromium-di-tetrahydrofuran]tetracarbonylcobaltate (1); (909553-60-2)

Carbon monoxide; (630-08-0)

Geoffrey W. Coates obtained a B.A. degree in chemistry from Wabash College in 1989 and a Ph.D. in organic chemistry from Stanford University in 1994. . He was an NSF Postdoctoral Fellow with Robert H. Grubbs at the California Institute of Technology. . In 1997 he joined the faculty of Cornell University as an Assistant Professor of Chemistry. . He was promoted to Associate Professor in 2001, and to Professor in 2002. . He was Associate Chair of Chemistry from 2004 to 2008 and was appointed as the first Tisch University Professor in 2008. . His research focuses on the development of catalysts for organic and polymer synthesis.
John W. Kramer was born in 1980 in East Troy, Wisconsin. In 2002 he earned his B.A. in Chemistry and Environmental Studies from Grinnell College, working under the guidance of Professor T. Andrew Mobley. In 2003 he began his graduate studies at Cornell University and joined the laboratory of Geoffrey W. Coates. His work in the Coates group has focused on the ring-expanding carbonylation of heterocycles for the synthesis of biologically relevant molecules. He is currently a Research Scientist at Dow Chemical in Midland, Michigan.
Daniel S. Treitler was born in Denville, New Jersey, in 1985. He joined the Coates group in 2005 as a sophomore at Cornell University. His research focused on the synthesis of substituted b-lactones and their polymerization to form new polyesters. From 2006 to 2007, he worked for Novomer, LLC where he optimized the large-scale synthesis of catalyst 1. Dan is currently pursuing his Ph.D. in organic chemistry at Columbia University.
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