Xúc tác Asymmetric với Nước: Giải Quyết Kinetics Hiệu Quả của các Epoxide Cuối Bằng Phương Pháp Thủy Phân Xúc Tác
Tóm tắt
Các epoxide là những khối xây dựng đa năng cho tổng hợp hữu cơ. Tuy nhiên, các epoxide đầu có thể được coi là phân nhóm quan trọng nhất của những hợp chất này, và hiện chưa có phương pháp tổng hợp tổng quát và thực tiễn nào cho việc sản xuất chúng dưới dạng tinh khiết đồng phân. Các epoxide đầu có sẵn với giá rất rẻ dưới dạng hỗn hợp racemic, và giải quyết động học là một chiến lược hấp dẫn cho việc sản xuất các epoxide quang hoạt, với một phương pháp kinh tế và dễ thực hiện. Các chất xúc tác tổng hợp có sẵn (các phức cobalt chiral dựa trên salen) đã được sử dụng cho quá trình thủy phân không đối xứng hiệu quả của các epoxide đầu. Quá trình này sử dụng nước làm tác nhân duy nhất, không có dung môi bổ sung, và nồng độ thấp của một chất xúc tác có thể tái chế (<0,5% mol), và nó cung cấp các epoxide đầu rất quý giá cũng như 1,2-diol với năng suất cao và sự làm giàu đồng phân cao.
Từ khóa
#epoxide #xúc tác không đối xứng #thủy phân #giải quyết động học #cobalt chiral #1 #2-diolTài liệu tham khảo
E. N. Jacobsen in Comprehensive Organometallic Chemistry II G. Wilkinson F. G. A. Stone E. W. Abel L. S. Hegedus Eds. (Pergamon New York 1995) vol. 12 chap. 11.1.
Aggarwal V. K., Ford J. G., Thompson A., Jones R. V. H., Standen M., J. Am. Chem. Soc. 118, 7004 (1996).
The highest enantioselectivity reported to date for the epoxidation of propylene is 41% [R. Sinigalia R. A. Michelin F. Pinna G. Strukul Organometallics 6 728 (1987)].
For leading references on kinetic resolution see E. L. Eliel S. H. Wilen L. M. Mander Stereochemistry of Organic Compounds (Wiley-Interscience New York 1994) pp. 395-415
H. B. Kagan and J. C. Fiaud in Topics in Stereochemistry N. L. Allinger and E. L. Eliel Eds. (Interscience New York 1987) vol. 14 p. 249.
Enantioselective hydrolysis of epoxides with the use of biocatalysts has received considerable attention [K. Faber Biotransformations in Organic Chemistry (Springer-Verlag New York 1992) chap. 2.1.5
Jacobsen E. N., Kakiuchi F., Konsler R. G., Larrow J. F., Tokunaga M., Tetrahedron Lett. 38, 773 (1997).
The kinetic resolution of epoxides with (CH 3 ) 3 SiN 3 with (salen)Cr complexes has been documented [
]. Despite the high selectivity observed in these kinetic resolutions this method is impractical for the recovery of enantiomerically enriched epoxide because it requires consumption of azide a relatively precious reagent.
Complex 2b can be generated in situ from 1 (7) by treatment with acetic acid (2 equiv) in toluene under air followed by evaporation of solvent. 1 H nuclear magnetic resonance (NMR) (400 MHz dry acetone- d 6 ) δ (ppm) relative to tetramethylsilane: −1.95 (br s 2 H H 2 O) 1.21 (s 9 H t -Bu) 1.28 (s 9 H t -Bu) 1.33 (s 9 H t -Bu) 1.53 (s 9 H t -Bu) 1.58 [s 3 H CH 3 C(O)] 1.6 (m 2 H CH 2 ) 1.9 to 2.0 (m 2 H CH 2 ) 2.23 (br q J = 9.8 Hz 1 H C H H) 2.79 (d J = 11.8 Hz 1 H C H H) 2.88 (br d 2 H CH 2 ) 3.27 (brt 1 H CHN) 4.35 (brt 1 H CHN) 7.17 (d J = 2.4 Hz 1 H ArH) 7.22 (s 1 H CH=N) 7.29 (d J = 2.4 Hz 1 H ArH) 7.35 (d J = 2.4 Hz 1 H ArH) 7.46 (d J = 2.4 Hz 1 H ArH) 7.59 (s 1 H CH=N). Infrared (KBr) 1719 w 1638 s 1611 s 1545 s 1540 s 1526 s 1461 s 1436 s 1408 s 1390 s 1361 s 1339 s 1323 s 1270 s 1255 s 1235 m 1202 m 1169 s 834 m 783 m; melting point (open capillary) 108°C (decomposes).
The hydrolysis reactions were mildly exothermic on a laboratory scale. For the kinetic resolution of propylene oxide (boiling point 34°C) the reaction vessel was cooled in an ice bath during the addition of water to limit substrate loss as a result of evaporation.
A mixture of ( S S )- 1 (1.208 g 2.0 mmol 0.2 mol %) toluene (10 ml) and acetic acid (0.23 ml 4.0 mmol 2 equiv to catalyst) was stirred while open to the air for 1 hour at room temperature. The solvent was removed by rotary evaporation and the brown residue was dried under vacuum. Propylene oxide (58.7 g 1.0 mol) was added in one portion and the stirred mixture was cooled in an ice-water bath. Water (9.9 ml 0.55 mol 0.55 equiv) was slowly added until the temperature of the reaction mixture began to rise. The temperature rose to ∼25°C before dropping to 15°C at which point water addition was continued at a rate that maintained the reaction temperature near 20°C. After 1 hour addition was complete; the ice bath was removed and the reaction was stirred at room temperature for 11 hours. The flask was then affixed with a distillation head equipped with a receiver cooled to −78°C and the unreacted epoxide was distilled under N 2 until no more material came over with gentle heating. The system was then placed in a mild vacuum to collect any residual epoxide [yield: 26.05 g >99% pure by gas chromatography (GC) 0.444 mol 44% yield]. The receiver was changed and the system was carefully placed in a full vacuum (<65 Pa). The diol was then distilled under vacuum into an ice-cooled receiver and isolated as a colorless viscous liquid (yield: 38.66 g >99% pure by GC 0.503 mol 50% recovery).
It is significant that propylene glycol is isolated in high enantiomeric purity and yield. Even though excellent methods exist for the asymmetric dihydroxylation (AD) of most olefins (5) the highest enantioselectivity obtained to date in the AD of propylene is only 49% [
For a practical method for the epoxidation of α-olefins see
The HKR of propylene oxide has been carried out successfully on a 10-kg scale at a pilot plant at Chirex Inc. (Dudley UK) (J. Cummins and G. Thorpe private communication).
This work was supported by a grant from the National Institutes of Health (GM-43214) and postdoctoral fellowships to M.T. and F.K. from the Japan Society for the Promotion of Science.