Dr. P. Wipf Chem /10/2007

Transcription

1 I. Basic Principles I-N. Epoxides 1. High-Valent TM(d0) Epoxidations Mo, V, W (H 2 WO 4 ), Ti, Al serve as catalysts with t-buo 2 H or other peroxides as stoichiometric oxidants. Toluene is a frequent solvent. Mo(CO) 6 is the catalyst of choice for substrates lacking directing groups. 1

2 More detailed references: Oshima, THL 1980, 21, 1657, 4843; Sharpless, THL 1979, 20, 4733; Kishi JACS 1978, 100,

3 The extent to which a hydroxyl group is involved in the epoxidation of cyclic alkenes and alkadienes is determined not only by its position relative to the double bond but also by the conformation of the molecule as a whole (Dryuk, V. G.; Kartsev, V. G., "Mechanism of the directing influence of functional groups and the geometry of reactant molecules on peroxide epoxidation of alkenes." Russ. Chem. Rev. 1999, 68, ): 2. Sharpless Asymmetric Epoxidation (SAE) 1980: Katsuki & Sharpless; Ti(IV)alkoxide, tartrate, t-buooh. References: Comprehensive Organic Synthesis 1991, vol. 7, chapter 3.2; pp 389; Chem. Rev. 1991, 91, 437. Org. React. 1996, 48,

4 mechanism: dimer is active species (Finn, M. G.; Sharpless, K. B. J. Am. Chem. Soc. 1991, 113, 112). incompatible functional groups: amines, -CO 2 H, -SH, phenols, phosphines. Stoichiometry: 5% Ti / 6% tartrate to 10% Ti / 12% tartrate: 4

5 Masamune, S.; Sharpless, K. B. Tetrahedron 1990, 46, 245. Total synthesis of L-hexoses. 5

6 Kinetic resolution of allylic alcohols (J. Am. Chem. Soc. 1981, 103, 6237). 6

7 Especially interesting in this context is the potential of the Sharpless asymmetric epoxidation in bi-directional synthesis and for the differentiation of diastereotopic alkenes: Assuming that no significant bisepoxidation has occurred after 3 h, the ee of this reaction would be 84% for the major product, and the de would be 87% (anti/syn) for the reaction. If we allow the reaction to proceed, the ee and de should increase! C ee 84% de 87% C ee 93% de 92% C ee >97% de >95% 7

8 Schreiber, S. L. et al. J. Am. Chem. Soc. 1987, 109, Twodirectional chain synthesis with end-group differentiation. For a general discussion of chain synthesis strategies, see: Poss, C. S.; Schreiber, S. L., "Two-directional chain synthesis and terminus differentiation." Acc. Chem. Res. 1994, 27, 9. Application in synthesis: Schreiber, S. L. et al. J. Org. Chem. 1989, 54, 15): 8

9 Preparation of starting diepoxide: Leung, L. M. H.; Gibson, V.; Linclau, B., "Improved synthesis of enantiopure pseudo-c2- symmetric 1,4-bis-epoxide building blocks from arabitol." Tetrahedron: Asymmetry 2005, 16, Moffat reagent (J. Am. Chem. Soc. 1973, 95, 4016): Related to Moffatt s reagent is the use of Viehe s reagent (Fraser-Reid, B. et al. Tetrahedron Lett. 1986, 27, 4697). 9

10 3. Jacobsen-Katsuki Epoxidations Jacobsen, JACS 1990, 112, 2801; JACS 1991, 113, 7063; Katsuki, THL 1990, 31, Based on Kochi s achiral salen catalyst. Mcgarrigle, E. M.; Gilheany, D. G., "Chromium- and manganesesalen promoted epoxidation of alkenes." Chem. Rev. 2005, 105, Application in process chemistry (THL 1995, 36, 3993): The use of the co-catalyst P 3 NO allowed for a decreased charge of the Mn salen catalyst in the Jacobsen epoxidation. P 3 NO stabilized the catalyst, increased the rate, and transported bulk oxidant HOCl into the organic phase (JOC 1997, 62, 2222). 10

11 Mechanistic considerations (Linker, T. Angew. Chem. Int. Ed. Engl. 1997, 36, 2060). Preferred directions of attack of alkenes according to Jacobsen (a) and Katsuki (b): 3 possible mechanisms regarding the oxygen transfer to the double bond: Epoxidation of styrene derivatives leads to mixtures: Radical clock experiments give conflicting results: There is clear evidence for the formation of radical intermediates, however, manganooxetanes, for which there is electrospray MS evidence, can also play a part in the mechanism. The influence of reaction conditions has to be taken into account. 11

12 Nielsen, L. P. C.; Stevenson, C. P.; Blackmond, D. G.; Jacobsen, E. N., "Mechanistic investigation leads to a synthetic improvement in the hydrolytic kinetic resolution of terminal epoxides (HKR)." J. Am. Chem. Soc. 2004, 126, The (salen)-co(iii) complex 1 provides a general and effective method for the preparation of enantioenriched terminal epoxides. 1a is the most commonly used variant. The catalyst shows a second-order dependence, and a cooperative bimetallic mechanism has been suggested: Dominant catalytic cycle in HKR reactions (RDS = rate determining step): 12

13 4. Peracid/Peroxide Epoxidations Standard peracids are: MCPBA, CH 3 CO 3 H, MMP, CF 3 CO 3 H, 3,5- dinitroperbenzoic acid. 13

14 Epoxidation under Payne conditions: Bachmann, C.; Gesson, J.-P.; Renoux, B.; Tranoy, I. Tetrahedron Lett. 1998, 39, 379. With the less acidic MCPBA, epoxidation of allylic ethers is directed by steric hindrance and is antiselective. Diastereomeric control in the epoxidation with peracids is quite good, if appropriate directing groups are present, or if the substrate is sterically biased. 14

15 Wipf, P.; Kim, Y.; Fritch, P. C. J. Org. Chem. 1993, 58, Diastereocontrol in acyclic substrates: Kishi, Y. et al. Tetrahedron Lett. 1980, 21,

16 mechanistic consideration of the relative stability of ground state conformational isomers: more calc.: Houk, K. N. J. Am. Chem. Soc. 1991, 113,

17 Catalytic Asymmetric Epoxidation with Chiral Dioxiranes Wang, Z.-Y.; Tu, Y.; Frohn, M.; Shi, Y. J. Org. Chem. 1997, 62, Biphasic reactions, inexpensive oxidants; turnover and catalytic efficiency need to be improved for this chemistry to become a viable competitor to transition metal catalysts for asymmetric epoxidation. For recent progress, see: J. Org. Chem. 1997, 62, Shi, Y., "Organocatalytic asymmetric - epoxidation of olefins by chiral ketones." Acc. Chem. Res. 2004, 37, Yang, D., "Ketone-catalyzed asymmetric epoxidation reactions." Acc. Chem. Res. 2004, 37,

18 Epoxidation of enones: H 2 O 2, t-buo 2 H, cumene hydroperoxide Ooi, T.; Ohara, D.; Tamura, M.; Maruoka, K., "Design of new chiral phase-transfer catalysts with dual functions for highly enantioselective epoxidation of α,β-unsaturated ketones." J. Am. Chem. Soc. 2004, 126, Presently limited to aryl or t-bu ketones 18

19 Kakei, H.; Tsuji, R.; Ohshima, T.; Shibasaki, M., "Catalytic asymmetric epoxidation of α,β-unsaturated esters using an yttrium-biphenyldiol complex." J. Am. Chem. Soc. 2005, 127, Alternative Methods for Epoxide Formations Epoxides from diols: Martin, T.; Soler, M. A.; Betancort, J. M.; Martin, V. S. J. Org. Chem. 1997, 62,

20 Gardinier, K. M.; Leahy, J. W. J. Org. Chem. 1997, 62, The basic transesterification required with standard esters in the final step of the Sharpless conversion of vicinal diols into epoxides (Kolb, H. C.; Sharpless, K. B. Tetrahedron 1992, 48, 10515) was incompatible with the target molecule (cryptophycin). Ireland, R. E.; Wipf, P.; Roper, T. D. J. Org. Chem. 1990, 55,

21 Via halohydrins: Cardillo-Epoxidation (TH 1990, 46, 3321): Guo, J.; Duffy, K. J.; Stevens, K. L.; Dalko, P. I.; Roth, R. M.; Hayward, M. M.; Kishi, Y. Angew. Chem. Int. Ed. 1998, 37,

22 Arai, S.; Shioiri, T., "Catalytic asymmetric Darzens condensation under phase-transfer-catalyzed conditions." Tetrahedron Lett. 1998, 39, Corey-Chaykovski Reaction: Aggarwal, V. K.; Ford, J. G.; Fonquerna, S.; Adams, H.; Jones, R. V. H.; Fieldhouse, R., "Catalytic Asymmetric Epoxidation of Aldehydes. Optimization, Mechanism, and Discovery of Stereoelectronic Control Involving a Combination of Anomeric and Cieplak Effects in Sulfur Ylide Epoxidations with Chiral 1,3-Oxathianes." J. Am. Chem. Soc. 1998, 120, Aggarwal, V. K.; Winn, C. L., "Catalytic, asymmetric sulfur ylidemediated epoxidation of carbonyl compounds: Scope, selectivity, and applications in synthesis." Acc. Chem. Res. 2004, 37,

23 6. Epoxide Opening Reactions Review: Hanson, R. M. Chem. Rev. 1991, 91, 437. on rings: trans-diaxial opening is preferred (Fürst-Plattner rule): 23

24 Wipf, P.; Lim, S. J. Am. Chem. Soc. 1995, 117, 558; Wipf, P.; Lim, S. Chimia 1996, 50, 157. Yamamoto, H. et al. J. Am. Chem. Soc. 1989, 111,