University:
Massachusetts Institute of Technology
Course:
5.37 | Introduction to Organic Synthesis Laboratory
Academic year:

2021
Views:

64

Pages:

5
Author:

Steve Pratt

Massachusetts Institute of Technology Organic Chemistry 5.37 Lecture 4 Introduction to Organic Synthesis The Diels-Alder Reaction, Part IV RE RZ RE EWG RZ R1 R'Z R2 R'E R'Z R'E EWG + R2 R1 Stereochemical Course of the Diels-Alder Reaction Intrinsic Stereoselectivity  Suprafacial with respect to the diene  Suprafacial with respect to the dienophile  Alder endo rule Asymmetric Induction  Substrate control by chiral dienophiles  Substrate control by chiral dienes  Stereocontrol via chiral auxiliaries Catalytic Asymmetric Cycloadditions Case Study Total Synthesis of Prostaglandins Corey, E. J.; Weinshenker, N. M.; Schaaf, T. K.; Huber, W. J. Am. Chem. Soc. 1969, 91, 5675 OH 9 8 CO2H CO2H 11 HO 12 HO OMe HO Key Subtarget Prostaglandin F2α Controlling the Relative Stereochemistry In the previous lecture, we saw how Corey's synthesis of prostaglandin F2α exploits two of the stereochemical features of the Diels-Alder reaction:  the intrinsic stereoselectivity (suprafacial addition with respect to the diene)  asymmetric induction (substrate control by the diene) Controlling the Absolute Stereochemistry  Approach I: Resolution Corey, E. J.; Schaaf, T. K.; Huber, W.; Koelliker, U.; Weinshenker, N. M. J. Am. Chem. Soc. 1970, 92, 397 Controlling the Absolute Stereochemistry  Approach II: Chiral Auxiliaries Corey, E. J.; Ensley, H. E. J. Am. Chem. Soc. 1975, 97, 6908 2.5 equiv BnO OCH2Ph H H BnO Ph H O H O 2 0.7 equiv AlCl3 CH2Cl2, -55 °C + CO2R* CO2R* 97:3 ratio major cycloadduct isolated in 89% yield also obtained 7% exo cycloadducts prepared in 4 steps from (-)-pulegone OH O 1) LDA, O2; then P(OEt)3 2) LiAlH4 3) NaIO4 BnO H (-)-Pulegone (-)-Menthol Peppermint "The Worlds's Oldest Medicine" O  Approach III: Catalytic Asymmetric Diels-Alder Reactions Example 1: Corey's "Stein" ("Stilbene Diamine") Catalyst Corey, E. J.; Imwinkelried, R.; Pikul, S.; Xiang, Y. B. J. Am. Chem. Soc. 1989, 111, 5493 Corey, E. J.; Imai, N.; Pikul, S. Tetrahedron Lett. 1991, 32, 7517 Corey, E. J.; Sarshar, S.; Bordner, J. J. Am. Chem. Soc. 1992, 114, 7938 ? equiv O H BnO OCH2Ph H BnO H N O O 2 H Ph Ph + O 0.1 equiv F3CO2S N N Al O SO2CF3 N O O N O Me (prepared in 7 steps) 98:2 ratio (96% ee) major cycloadduct isolated in 93% yield CH2Cl2, -78 °C, 18 h BnO 1) LiOH, aq H2O2 2) MsOH, EtOH HC(OEt)3 H H CO2Et O  Approach III: Catalytic Asymmetric Diels-Alder Reactions Example 2: Yamamoto's "CAB" ("Chiral Acyloxy Borane") Catalyst Ishihara, K.; Gao, Q.; Yamamoto, H. J. Org. Chem. 1993, 58, 6917 Furuta, K.; Gao, Q.-Z.; Yamamoto, H. Org. Synth. 1995, 72, 86 Furuta, K.; Shimizu, S.; Miwa, Y.; Yamamoto, H. J. Org. Chem. 1989, 54, 1481 Furuta, K.; Miwa, Y.; Iwanaga, K.; Yamamoto, H. J. Am. Chem. Soc. 1988, 110, 6254 O O BH O HO2C O O R 4 equiv Br CHO CHO 0.1 equiv CAB CHO CH2Cl2, -78 °C, 10 h + Br Br 97.5:2.5 ratio (95% ee) 100% yield 94:6 exo/endo cycloadducts Corey, E. J.; Loh, T.-P. J. Am. Chem. Soc. 1991, 113, 8966 BnO H 1) NH2OH-HCl, aq THF, pH 4 2) TsCl, pyr 3) NaOH, H2O BnO H CHO Br O

Introduction to Organic Synthesis: The Diels-Alder Reaction, Part IV

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