Enantioselective Organocatalytic Epoxidation Using Hypervalent Iodine Reagents
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Tetrahedron 62 (2006) 11413–11424 Enantioselective organocatalytic epoxidation using hypervalent iodine reagents Sandra Lee and David W. C. MacMillan* Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA Received 29 June 2006; accepted 12 July 2006 Available online 23 August 2006 Abstract—A rare example of a hypervalent iodine reagent participating in a 1,4-heteroconjugate addition reaction is reported for the organo- catalytic, asymmetric epoxidation of a,b-unsaturated aldehydes using imidazolidinone catalyst 1. Development of an ‘internal syringe pump’ effect via the slow release of iodosobenzene from an iminoiodinane source provides high levels of reaction efficiency and enantiomeric control in the asymmetric epoxidation of electron-deficient olefins. 15N NMR studies were conducted to elucidate the reaction pathways that lead to catalyst depletion in the presence of prototypical oxidants. These NMR studies also provided the mechanistic foundation for the application of iminoiodinanes as an internal slow release oxidant to circumvent these catalyst depletion pathways. Ó 2006 Elsevier Ltd. All rights reserved. 1. Introduction upon the Weitz–Scheffer reaction,10 wherein a nucleophilic chiral peroxide adds to an enone or enal (Fig. 1). This strat- The enantioselective catalytic oxidation of olefins is argu- egy of hydroperoxide delivery via a homogeneous chiral ably one of the most powerful transformations known to metal complex has been adopted and developed by Enders11 practitioners of chemical synthesis.1 Indeed, since the inven- in a stoichiometric manner and in a catalytic approach by tion of the Sharpless asymmetric epoxidation,2 there has Jackson12 and Shibasaki.13 Alternatively, asymmetric phase been an ever-increasing demand for catalyst-controlled transfer agents have been utilized to transport a reactive processes that allow efficient and predictable access to oxo-species to olefin substrates as epitomized in the work enantioenriched oxiranes. Significant efforts to expand the of Roberts14 using polyamino acids and in the cinchona scope of such catalytic epoxidations have been made via alkaloid-derived salts of Lygo15 and Corey.16 the seminal contributions of Jacobsen3 and Katsuki4 using metal-ligated systems for the electrophilic delivery of oxy- gen. Complementary to these established organometallic strategies, Shi,5 Denmark,6 Yang,7 and Armstrong8 have de- Mg-Catalyzed Jackson Epoxidation O R' veloped an elegant organocatalytic approach that relies upon R' OH catalyst O EtO a ketone-derived dioxirane catalyst for the asymmetric epoxi- MgBu2 R O R O EtO dation of trisubstituted and 1,2-trans-disubstituted alkenes. TBHP, 4Å MS OH O These epoxidation methods are applicable to several olefin R = aryl, alkyl; R' = Me, Et, aryl 81–94% ee classes; however, they do not encompass the enantioselec- tive epoxidation of electron-deficient olefins. Ln-BINOL Catalyzed Shibasaki Epoxidation Enantioselective Catalytic Epoxidation of Olefins R Ln(O-iPr)3 OR' OR' Ln = La,Yb oxidant, catalyst O OH R O asymmetric O CMHP or TBHP R O OH organometallic or 4Å MS R = H, CH2OH organocatalyst R = Ph, Me, i-Pr; R' = alkyl, Ph 83–94% ee epoxide products = stereodefined sp3 electrophile versatile electrophile for chemical synthesis applications Corey Phase-Transfer Epoxidation Me OBn OR' OR' Existing technologies for the enantioselective epoxidation of O N 9 catalyst olefins via LUMO-lowering activation have been founded R O Br KOCl R O N n Keywords: Epoxidation; Organocatalysis; Enantioselective; Iodosobenzene. R = aryl, Cy, -C5H11; R' = aryl 91–99% ee * Corresponding author. Tel.: +1 626 395 6044; fax: +1 626 795 3658; e-mail: [email protected] Figure 1. General methods for catalytic nucleophilic epoxidations. 0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2006.07.055 11414 S. Lee, D. W. C. MacMillan / Tetrahedron 62 (2006) 11413–11424 Most recently, Jørgensen and co-workers17 have demon- cyclopropanation studies that were ongoing in our labora- strated the asymmetric organocatalytic epoxidation of a,b- tory.19a In that methodology, a pendent thionium moiety unsaturated aldehydes using iminium catalysis. In these functions as a suitable leaving group for intramolecular en- elegant studies, a variety of enals rapidly underwent asym- amine cyclization to yield three-membered carbocycles. metric epoxidation using hydrogen peroxide as the stoichio- With this in mind, we recognized that an analogous epoxi- metric oxidant in the presence of a proline-derived catalyst. dation mechanism would rely on the judicious selection of In this publication, we further demonstrate the use of our chi- an ambiphilic oxygen source that could function as a viable ral imidazolidinone salts as iminium activation catalysts for nucleophile for the conjugate addition step, yet would be the asymmetric epoxidation of a,b-unsaturated aldehydes. suitably electrophilic (via incorporation of an electronega- This transformation provides rapid access to enantio- tive leaving group (LG)) to enable intramolecular enamine enriched 1,2-trans-formyl epoxides, an ambiphilic class of oxidation and oxirane formation. electrophile of known value in chemical synthesis.18 2. Results and discussion In 2002, we initiated studies to develop a novel organocata- lytic strategy for the asymmetric epoxidation of electron- 2.1. Preliminary investigations deficient olefins based upon the activation principle of iminium catalysis. Having demonstrated the capacity of chi- Our studies began with an investigation to define potential ral amines to function as asymmetric catalysts and building oxygen sources that would participate in the requisite 1,4- on previous successes in cycloadditions and 1,4-conjugate 19 heteroconjugate addition/enamine cyclization. Initial exper- additions, it was anticipated that a nucleophilic oxygen iments were performed with crotonaldehyde and a variety of that incorporated a suitable leaving group could add with commercially available oxidants in the presence of catalyst enantiofacial selectivity to an iminium-activated a,b-unsatu- 1$trifluoroacetic acid (TFA) salt. To our delight, the desired rated aldehyde (Fig. 2). Subsequent enamine formation 2,3-epoxyaldehyde product (2) was readily accessed using followed by intramolecular trapping of the pendent electro- a variety of oxygen sources (Table 1). Implementation of philic oxygen with concomitant expulsion of the oxygen- m-CPBA provided the epoxide product 2 with encouraging tethered leaving group should then produce an oxirane selectivity levels (Table 1, entry 3, 73% ee); however, studies (Fig. 3). At the outset of these studies, we felt that the pro- to define the utility of this reagent (solvent, temperature) re- posed cyclization step had good precedent given related sulted in little improvement in overall enantiocontrol. The use of peroxides, such as tert-butyl hydrogen peroxide and hydrogen peroxide20 also provided the desired oxirane with notable enantioselectivities (Table 1, entries 4 and 5). OMe However, attempts to employ such oxidants with less reac- N X tive substrates (such as cinnamaldehyde) resulted mainly Me N in the production of the catalyst N-oxide derivative, a catalyst Me Ph Me depletion pathway that significantly reduces reaction effi- X ciency. Unfortunately, bleach and pyridine N-oxide were Si- R face Re-face not found to be viable reagents for this process (Table 1, blocked exposed catalyst-aldehyde entry 6). iminium complex OLG We next examined the use of hypervalent l3-iodanes as Figure 2. Rationale of catalyst-controlled enantioselectivity utilizing an potential oxidants for this organocatalytic Weitz–Scheffer MM3-2 model of the catalyst. reaction. While iodosobenzene is routinely employed as an oxygen transfer agent in metal-oxo mediated epoxidations,21 Me O O N •HX Me O Me Table 1. Initial survey of oxygen sources for epoxidation O Me N 20 mol% 1•TFA Me H O Me Ph oxidant (1 eq) H2O H O catatyst 1 2 O Me O Me CH2Cl2 (0.2 M) 18 h, –30 °C (3 equiv) 2 Me O Me O N X N X a b Me Me Entry Oxidant % Conversion %ee N N Me Me 1 Pyridine N-oxide NR — Me Ph Me Ph 2 OXONEÒ NR — O iminium 3 m-CPBA 34 73 R Me O R 4 t-BuOOHc 35 69 N d 5H2O2 959 Me e N 6 NaOCl 90 Me 7 PhI]O4372 LG Me Ph OLG LG a enamine O Conversion determined by GC relative to methyl benzyl ether. b R Enantiomeric excess determined by chiral GC analysis (Chiraldex G-TA). c Used as 5 M solution in decane. Figure 3. Proposed organocatalytic cycle for oxirane formation and the d Used as a 50% solution in water. generation of an a,b-epoxy aldehyde. e Used as a 5.25% solution in water. S. Lee, D. W. C. MacMillan / Tetrahedron 62 (2006) 11413–11424 11415 Table 2. Effect of solvent on the epoxidation reaction Table 3. Effect of acid co-catalyst on the epoxidation reaction 20 mol% 1•TFA 20 mol% 1•TFA O O PhI=O (1 eq) PhI=O (1 eq) O Me O Me O Me O Me solvent (0.2 M) CH2Cl2 (0.2 M) 20 h, –30 °C 18 h, –30 °C (3 equiv) 2 (3 equiv) 2 a b c a b Entry Solvent 3 % Conversion %ee Entry HX pKa % Conversion %ee 1 DMF (10% H2O) — 87 25 1 TfOH À14 74 87 2 MeCN 36.6 55 33 2 HClO4 À10 68 88 3 Acetone 21.0 41 42 3 p-TSAc À2.6 50 76 4CH2Cl2 8.9 50 80 4TFAÀ0.3 42 72 5 THF 7.5 14 76 5 DCAd 1.3 27 72 e 6 THF (10% H2O) — 12 75 6CNA2.5 27 69 7 CHCl 4.8 45 82 3 a 8 Ether 4.3 29 63 Conversion determined by GC relative to benzyl ether. b 9 Toluene 2.4 63 64 Enantiomeric excess determined by chiral GC analysis (Chiraldex G-TA). c p-Toluenesulfonic acid. a See Ref. 38. d Dichloroacetic acid. b Conversion determined by GC relative to tridecane.